Trial Outcomes & Findings for Study of Pregnyl as Adjunct Therapy for High-Risk or Refractory Acute GVHD (NCT NCT02525029)

Last Updated: 2023-12-14

Results Overview

Maximum tolerated dose (MTD) of Pregnyl® when given with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory acute graft-versus-host disease (aGVHD). Dosage measured as (USP hCG/pg EGF/mm\^2).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

53 participants

Primary outcome timeframe

Day 14 after initiation of protocol therapy

Results posted on

2023-12-14

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Overall Study STARTED	2	2	9	13	1	4	8	2	1	5	1	2	3
Overall Study COMPLETED	2	2	9	13	1	4	8	1	1	5	1	2	3
Overall Study NOT COMPLETED	0	0	0	0	0	0	0	1	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Pregnyl as Adjunct Therapy for High-Risk or Refractory Acute GVHD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=9 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=4 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=8 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=5 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m n=3 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Total n=53 Participants Total of all reporting groups
Age, Continuous	46 Years n=5 Participants	64 Years n=7 Participants	60.5 Years n=5 Participants	60.5 Years n=4 Participants	57 Years n=21 Participants	61.5 Years n=10 Participants	61.5 Years n=115 Participants	56.5 Years n=6 Participants	63 Years n=6 Participants	64 Years n=64 Participants	64 Years n=17 Participants	61 Years n=21 Participants	50 Years n=22 Participants	61 Years n=8 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	3 Participants n=115 Participants	1 Participants n=6 Participants	0 Participants n=6 Participants	1 Participants n=64 Participants	1 Participants n=17 Participants	0 Participants n=21 Participants	0 Participants n=22 Participants	14 Participants n=8 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	10 Participants n=4 Participants	1 Participants n=21 Participants	3 Participants n=10 Participants	5 Participants n=115 Participants	1 Participants n=6 Participants	1 Participants n=6 Participants	4 Participants n=64 Participants	0 Participants n=17 Participants	2 Participants n=21 Participants	3 Participants n=22 Participants	39 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=64 Participants	0 Participants n=17 Participants	0 Participants n=21 Participants	1 Participants n=22 Participants	3 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants	13 Participants n=4 Participants	1 Participants n=21 Participants	4 Participants n=10 Participants	7 Participants n=115 Participants	2 Participants n=6 Participants	1 Participants n=6 Participants	5 Participants n=64 Participants	1 Participants n=17 Participants	2 Participants n=21 Participants	2 Participants n=22 Participants	50 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=64 Participants	0 Participants n=17 Participants	0 Participants n=21 Participants	0 Participants n=22 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=64 Participants	0 Participants n=17 Participants	0 Participants n=21 Participants	0 Participants n=22 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=64 Participants	0 Participants n=17 Participants	0 Participants n=21 Participants	0 Participants n=22 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=64 Participants	0 Participants n=17 Participants	0 Participants n=21 Participants	0 Participants n=22 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=64 Participants	0 Participants n=17 Participants	0 Participants n=21 Participants	0 Participants n=22 Participants	2 Participants n=8 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants	12 Participants n=4 Participants	1 Participants n=21 Participants	3 Participants n=10 Participants	7 Participants n=115 Participants	2 Participants n=6 Participants	1 Participants n=6 Participants	5 Participants n=64 Participants	0 Participants n=17 Participants	2 Participants n=21 Participants	3 Participants n=22 Participants	46 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=64 Participants	0 Participants n=17 Participants	0 Participants n=21 Participants	0 Participants n=22 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants	0 Participants n=64 Participants	1 Participants n=17 Participants	0 Participants n=21 Participants	0 Participants n=22 Participants	3 Participants n=8 Participants
Region of Enrollment United States	2 participants n=5 Participants	2 participants n=7 Participants	9 participants n=5 Participants	13 participants n=4 Participants	1 participants n=21 Participants	4 participants n=10 Participants	8 participants n=115 Participants	2 participants n=6 Participants	1 participants n=6 Participants	5 participants n=64 Participants	1 participants n=17 Participants	2 participants n=21 Participants	3 participants n=22 Participants	53 participants n=8 Participants

PRIMARY outcome

Timeframe: Day 14 after initiation of protocol therapy

Outcome measures

Outcome measures
Measure	1: High-Risk aGVHD n=26 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2a: Steroid-Dependent aGVHD n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2b: Steroid-Refractory aGVHD n=12 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Phase I: MTD (USP hCG)	2000 Pregnyl dosage (USP hCG)	2000 Pregnyl dosage (USP hCG)	5000 Pregnyl dosage (USP hCG)	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 14 after initiation of protocol therapy

Outcome measures

Outcome measures
Measure	1: High-Risk aGVHD n=26 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2a: Steroid-Dependent aGVHD n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2b: Steroid-Refractory aGVHD n=12 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Phase I: MTD (pg EGF/m^2)	14000 Pregnyl dosage (pg EGF/m^2)	14000 Pregnyl dosage (pg EGF/m^2)	34000 Pregnyl dosage (pg EGF/m^2)	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 28 after initiation of protocol therapy

Percentage of complete response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Complete response is defined as a Stage of 0 for all organs with no additional intervening therapy for their GVHD.

Outcome measures

Outcome measures
Measure	1: High-Risk aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2a: Steroid-Dependent aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2b: Steroid-Refractory aGVHD n=9 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=4 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=8 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=5 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 n=3 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Number of Patients With Complete Response	2 participants	2 participants	4 participants	7 participants	1 participants	3 participants	5 participants	1 participants	0 participants	2 participants	0 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: Day 28 after initiation of protocol therapy

Percentage of partial response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Partial response is defined as improvement by at least 1 stage in all involved organs without progression in others with no additional intervening therapy for their GVHD.

Outcome measures

Outcome measures
Measure	1: High-Risk aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2a: Steroid-Dependent aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2b: Steroid-Refractory aGVHD n=9 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=4 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=8 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=5 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 n=3 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Number of Patients With Partial Response	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants	1 participants	0 participants	1 participants	1 participants	0 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: Day 28 after initiation of protocol therapy

Percentage of mixed response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. Mixed Response is defined as improvement in one organ with deterioration in another organ manifesting symptoms of GVHD or development of symptoms of GVHD in a new organ.

Outcome measures

Outcome measures
Measure	1: High-Risk aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2a: Steroid-Dependent aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2b: Steroid-Refractory aGVHD n=9 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=4 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=8 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=5 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 n=3 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Number of Patients With Mixed Response	0 participants	0 participants	1 participants	2 participants	0 participants	0 participants	2 participants	0 participants	0 participants	1 participants	1 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Day 28 after initiation of protocol therapy

Percentage of no response among surviving patients at day 28 after initiation of protocol therapy in pediatric and adult patients with high-risk (Arm 1) or refractory (Arm 2) aGVHD. No response is defined as deterioration of any organ involved.

Outcome measures

Outcome measures
Measure	1: High-Risk aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2a: Steroid-Dependent aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2b: Steroid-Refractory aGVHD n=9 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=4 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=8 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=5 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 n=3 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Number of Patients With No Response	0 participants	0 participants	4 participants	3 participants	0 participants	1 participants	0 participants	0 participants	0 participants	1 participants	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Day 70 after initiation of protocol therapy

Safety and feasibility of hCG supplementation with Pregnyl® in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk or refractory aGVHD.

Outcome measures

Outcome measures
Measure	1: High-Risk aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2a: Steroid-Dependent aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2b: Steroid-Refractory aGVHD n=9 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=4 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=8 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=5 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 n=3 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Number of Participants With Adverse Events as a Measure of Safety and Feasibility of hCG Supplementation With Pregnyl®	1 Participants	1 Participants	3 Participants	6 Participants	1 Participants	2 Participants	5 Participants	2 Participants	1 Participants	3 Participants	1 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 28 after initiation of protocol therapy

Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at day 28.

Outcome measures

Outcome measures
Measure	1: High-Risk aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2a: Steroid-Dependent aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2b: Steroid-Refractory aGVHD n=9 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=4 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=8 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=5 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 n=3 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Number of Participants With Incidence of aGVHD Flare	0 participants	0 participants	3 participants	5 participants	0 participants	0 participants	1 participants	0 participants	0 participants	0 participants	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Day 56 after initiation of protocol therapy

Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment at day 56.

Outcome measures

Outcome measures
Measure	1: High-Risk aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2a: Steroid-Dependent aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2b: Steroid-Refractory aGVHD n=9 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=4 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=8 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=5 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 n=3 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Number of Participants With Incidence of aGVHD Flare	0 participants	0 participants	2 participants	8 participants	0 participants	1 participants	4 participants	0 participants	0 participants	0 participants	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Day 28 after initiation of protocol therapy

Rate of treatment failure for acute GVHD at day 28 after initiation of protocol therapy to historical controls.

Outcome measures

Outcome measures
Measure	1: High-Risk aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2a: Steroid-Dependent aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2b: Steroid-Refractory aGVHD n=9 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=4 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=8 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=5 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 n=3 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Rate of Participants Who Fail Treatment at Day 28	0 participants	0 participants	8 participants	0 participants	0 participants	1 participants	0 participants	1 participants	0 participants	3 participants	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Day 56 after initiation of protocol therapy

Rate of treatment failure for acute GVHD at day 56 after initiation of protocol therapy to historical controls.

Outcome measures

Outcome measures
Measure	1: High-Risk aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2a: Steroid-Dependent aGVHD n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	2b: Steroid-Refractory aGVHD n=9 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m2 Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=13 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=4 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=8 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=5 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m^2 n=1 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m^2 n=2 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m^2 n=3 Participants Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment.
Rate of Participants Who Fail Treatment at Day 56	0 participants	0 participants	2 participants	9 participants	0 participants	2 participants	4 participants	1 participants	0 participants	2 participants	1 participants	1 participants	1 participants

Deaths: 1 deaths

Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m

Serious events: 3 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=2 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=9 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=13 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=4 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=8 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=5 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 2 Dose Level 3 2,000 USP n=1 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2 n=2 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m n=3 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.
Blood and lymphatic system disorders blood and lympathic system	0.00% 0/2 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Blood and lymphatic system disorders Leukocytosis	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Cardiac disorders Atrial Fibrillation	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	100.0% 1/1 • Number of events 2 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 3 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Colitis	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Colonic hemorrhage	50.0% 1/2 • Number of events 3 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Gastrointestinal disorders Colonic perforation	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Duode0l obstruction	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Duode0l perforation	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Enterocolitis	0.00% 0/2 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Gastrointesti0l disorders - Other,	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
General disorders Multi-organ failure	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Hepatobiliary disorders Cholecystitis	0.00% 0/2 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Hepatobiliary disorders Gallbladder pain	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Hepatobiliary disorders Hepatobiliary disorders - Other,	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Catheter related infection	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Enterocolitis infectious	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Infections and infestations - Other,	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	100.0% 2/2 • Number of events 3 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Lung infection	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	66.7% 2/3 • Number of events 2 • 70 Days after first treatment
Infections and infestations Peritoneal infection	0.00% 0/2 • 70 Days after first treatment	50.0% 1/2 • Number of events 2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Sepsis	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	100.0% 2/2 • Number of events 2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Metabolism and nutrition disorders Anorexia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/2 • 70 Days after first treatment	50.0% 1/2 • Number of events 2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Nervous system disorders Encephalopathy	50.0% 1/2 • Number of events 2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Nervous system disorders Reversible posterior	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Nervous system disorders Syncope	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	100.0% 1/1 • Number of events 2 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Vascular disorders Thromboembolic event	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment

Other adverse events

Other adverse events
Measure	Arm 1: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=2 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=9 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 7 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort has reached day 21 to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has a toxicity, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 1: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=13 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2A: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2A: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=4 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2A: Phase 2 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=8 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 1 500 USP hCG/3,500 pg EGF/m^2 n=2 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 2 1,000 USP hCG/7,000 pg EGF/m^2 n=1 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 3 2,000 USP hCG/14,000 pg EGF/m2 n=5 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 2 Dose Level 3 2,000 USP n=1 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 4 3,500 USP hCG/24,500 pg EGF/m2 n=2 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.	Arm 2B: Phase 1 Dose Level 5 5,000 USP hCG/35,000 pg EGF/m n=3 participants at risk Standard of care immunosuppression, plus Pregnyl® (hCG supplementation) at assigned dose subcutaneously every other day for up to 5 doses of Pregnyl®; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. The 1st 2 patients will be enrolled in dose level 1. The next cohort of 2 patients will not begin treatment until all patients in the current cohort have reached day 21 in order to assess for dose limiting toxicity (DLT). Individual patient dose reductions: If a patient has toxicity that meets the definition of dose limiting, the patient can drop down one dose level for the next injection and continue treatment. Pregnyl®: Standard of care immunosuppression, plus Pregnyl® at assigned dose subcutaneously every other day for up to 5 doses through day 7 Phase I: up to 7 dose levels of Pregnyl® will be tested; however dose levels -1 and -2 will be used only if dose level 1 proves too toxic. Study will use Continual Reassessment Method (CRM) to establish a maximum tolerated dose (MTD). Step -2: 125 USP hCG/875 pg EGF/m2 Step -1: 250 USP hCG/1,750 pg EGF/m2 Step 1 (start): 500 USP hCG/3,500 pg EGF/m2 Step 2: 1,000 USP hCG/7,000 pg EGF/m2 Step 3: 2,000 USP hCG/14,000 pg EGF/m2 Step 4 (Arm 2b only): 3,500 USP hCG/24,500 pg EGF/m2 Step 5 (Arm 2b only): 5,000 USP hCG/35,000 pg EGF/m Phase II: the dose of Pregnyl will be that identified as the MTD during phase I.
Blood and lymphatic system disorders Anemia	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Cardiac disorders Atrial fibrillation	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	100.0% 1/1 • Number of events 4 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Cardiac disorders Palpitations	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Cardiac disorders Supraventricular tachycardia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Ear and labyrinth disorders Ear pain	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Ear and labyrinth disorders Middle ear inflammation	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Endocrine disorders Adrenal insufficiency	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Eye disorders Blurred vision	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Eye disorders Conjunctivitis	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Eye disorders Dry eye	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Eye disorders Photophobia	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Eye disorders Watering eyes	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Abdominal distension	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	15.4% 2/13 • Number of events 3 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Abdominal pain	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	22.2% 2/9 • Number of events 2 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	50.0% 1/2 • Number of events 2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Ascites	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	15.4% 2/13 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Bloating	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Colitis	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Colonic hemorrhage	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Colonic perforation	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Constipation	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	50.0% 1/2 • Number of events 2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Diarrhea	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Duodenal obstruction	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Duodenal perforation	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Gastroesophageal reflux disease	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Hemorrhoidal hemorrhage	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Ileus	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Lip pain	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Lower gastrointestinal hemorrhage	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Mucositis oral	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Nausea	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Oral hemorrhage	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Oral pain	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Pancreatitis	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Rectal fistula	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Gastrointestinal disorders Vomiting	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
General disorders Edema face	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
General disorders Edema limbs	0.00% 0/2 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	22.2% 2/9 • Number of events 2 • 70 Days after first treatment	30.8% 4/13 • Number of events 10 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	37.5% 3/8 • Number of events 3 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 2 • 70 Days after first treatment
General disorders Edema trunk	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 3 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	50.0% 1/2 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
General disorders Fatigue	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 2 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	100.0% 2/2 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
General disorders Fever	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
General disorders Injection site reaction	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
General disorders Non-cardiac chest pain	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	25.0% 2/8 • Number of events 2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Hepatobiliary disorders Cholecystitis	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Hepatobiliary disorders Hepatic failure	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Bladder infection	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	15.4% 2/13 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Catheter related infection	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Conjunctivitis infective	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Encephalitis infection	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Enterocolitis infectious	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	15.4% 2/13 • Number of events 3 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Infections and infestations Hepatic infection	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Infections and infestations - Other, specify	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 2 • 70 Days after first treatment
Infections and infestations Lip infection	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Lung infection	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 2 • 70 Days after first treatment
Infections and infestations Periorbital infection	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Sepsis	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Infections and infestations Sinusitis	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Infections and infestations Upper respiratory infection	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	50.0% 2/4 • Number of events 2 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 2 • 70 Days after first treatment
Infections and infestations Urinary tract infection	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Investigations Alanine aminotransferase increased	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	23.1% 3/13 • Number of events 3 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	25.0% 2/8 • Number of events 2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Investigations Alkaline phosphatase increased	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Investigations Aspartate aminotransferase increased	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	15.4% 2/13 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Investigations Blood bilirubin increased	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 2 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 2 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Investigations Creatinine increased	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	23.1% 3/13 • Number of events 3 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Investigations Electrocardiogram QT corrected interval prolonged	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Investigations Fibrinogen decreased	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Investigations INR increased	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Investigations Investigations - Other, specify	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Investigations Platelet count decreased	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Investigations White blood cell decreased	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Metabolism and nutrition disorders Anorexia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Metabolism and nutrition disorders Hyperglycemia	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	23.1% 3/13 • Number of events 4 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	25.0% 2/8 • Number of events 2 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Metabolism and nutrition disorders Hypernatremia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 3 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Metabolism and nutrition disorders Hypoalbuminemia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	22.2% 2/9 • Number of events 3 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Metabolism and nutrition disorders Hypoglycemia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 2 • 70 Days after first treatment
Metabolism and nutrition disorders Hypokalemia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Metabolism and nutrition disorders Hypomagnesemia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Metabolism and nutrition disorders Hypophosphatemia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/2 • 70 Days after first treatment	50.0% 1/2 • Number of events 3 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	15.4% 2/13 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	50.0% 2/4 • Number of events 3 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Nervous system disorders Concentration impairment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Nervous system disorders Dizziness	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Nervous system disorders Dysgeusia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Nervous system disorders Headache	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	15.4% 2/13 • Number of events 3 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	12.5% 1/8 • Number of events 2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Nervous system disorders Lethargy	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Nervous system disorders Movements involuntary	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	15.4% 2/13 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 3 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 2 • 70 Days after first treatment
Nervous system disorders Sinus pain	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Nervous system disorders Syncope	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Nervous system disorders Tremor	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Psychiatric disorders Agitation	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Psychiatric disorders Confusion	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	15.4% 2/13 • Number of events 5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Psychiatric disorders Depression	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	23.1% 3/13 • Number of events 3 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Psychiatric disorders Hallucinations	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	100.0% 1/1 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Psychiatric disorders Insomnia	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	23.1% 3/13 • Number of events 3 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Renal and urinary disorders Acute kidney injury	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	23.1% 3/13 • Number of events 4 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Renal and urinary disorders Cystitis noninfective	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Renal and urinary disorders Urinary frequency	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Renal and urinary disorders Urinary retention	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Renal and urinary disorders Urinary tract obstruction	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Reproductive system and breast disorders Erectile dysfunction	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Cough	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	40.0% 2/5 • Number of events 3 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Epistaxis	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	50.0% 1/2 • Number of events 2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Respiratory, thoracic and mediastinal disorders Sore throat	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	25.0% 2/8 • Number of events 2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	11.1% 1/9 • Number of events 1 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 2 • 70 Days after first treatment
Skin and subcutaneous tissue disorders Skin ulceration	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	50.0% 1/2 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Vascular disorders Hot flashes	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Vascular disorders Hypertension	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	22.2% 2/9 • Number of events 3 • 70 Days after first treatment	30.8% 4/13 • Number of events 4 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	12.5% 1/8 • Number of events 1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	33.3% 1/3 • Number of events 1 • 70 Days after first treatment
Vascular disorders Hypotension	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	7.7% 1/13 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/4 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	20.0% 1/5 • Number of events 1 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment
Vascular disorders Lymphedema	0.00% 0/2 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/9 • 70 Days after first treatment	0.00% 0/13 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	25.0% 1/4 • Number of events 1 • 70 Days after first treatment	0.00% 0/8 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/5 • 70 Days after first treatment	0.00% 0/1 • 70 Days after first treatment	0.00% 0/2 • 70 Days after first treatment	0.00% 0/3 • 70 Days after first treatment

Additional Information

Dr. Shernan Holtan, MD

University of Minnesota, Masonic Cancer Center

Phone: (612) 626-5654

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place