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

NCT ID: NCT02525029

Last Updated: 2023-12-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

53 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2022-04-30

Brief Summary

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The purpose of this study is to determine the maximum tolerated dose (MTD) of Pregnyl® when given in combination with standard immunosuppressive therapy in pediatric and adult patients with high-risk (Arm 1) or refractory/dependent (Arm 2) aGVHD.

Detailed Description

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Conditions

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Graft vs Host Disease

Keywords

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GVHD

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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Arm 1: Phase 1 Dose Level -2: 125 USP hCG/875 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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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 I Dose Level -1: 250 USP hCG/1,750 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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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 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.

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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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/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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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: 125 USP hCG/875 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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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 I Dose Level -1: 250 USP hCG/1,750 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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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 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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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/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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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: 125 USP hCG/875 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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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 I Dose Level -1: 250 USP hCG/1,750 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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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/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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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/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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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^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.

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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 MTD

After completion of the dose finding trial for each arm, the final doses will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of the activity level for Arm 1 and Arm 2. If the phase I trial enrolls fewer than 13 patients at the MTD, we will employ Simon's Minmax two-stage design with the possibility to discontinue after the 1st stage if the response rate is low

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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: MTD

After completion of the dose finding trial for each arm, the final doses will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of the activity level for Arm 1 and Arm 2. If the phase I trial enrolls fewer than 13 patients at the MTD, we will employ Simon's Minmax two-stage design with the possibility to discontinue after the 1st stage if the response rate is low

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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: MTD

After completion of the dose finding trial for each arm, the final doses will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of the activity level for Arm 1 and Arm 2. If the phase I trial enrolls fewer than 13 patients at the MTD, we will employ Simon's Minmax two-stage design with the possibility to discontinue after the 1st stage if the response rate is low

Group Type EXPERIMENTAL

Pregnyl®

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Human chorionic gonadotropin (hCG)

Eligibility Criteria

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Inclusion Criteria

* Acute graft versus host disease (GVHD) fitting one of the following categories:

* High-Risk aGVHD (ARM 1): Pediatric or adult (ages 12-76 years) HCT recipients with high-risk acute GVHD, as determined by the refined MN acute GVHD risk score: http://z.umn.edu/MNAcuteGVHDRiskScore OR high risk on the basis of blood biomarkers (Ann Arbor Score 3 or amphiregulin ≥ 33 pg/ml) or
* Steroid-Refractory aGVHD (ARM 2): Pediatric or adult (ages 12-76 years) HCT recipient with grade II-IV steroid refractory or steroid-dependent acute GVHD, defined as any one of the following:

* No response of acute GVHD after at least 4 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
* Progression of acute GVHD within 3 days of systemic corticosteroids of at least 2 mg/kg prednisone or equivalent
* Failure to improve to at least grade II acute GVHD after 14 days of systemic corticosteroids, with initial doses of at least 2 mg/kg prednisone or equivalent
* Flare of acute GVHD of at least grade II/IV severity despite tapering dose of steroids being \> 0.5 mg/kg/day.
* Adequate organ function at study enrollment defined as:

* Renal: 1.73m2Serum creatinine ≤2.5x upper limit of normal (ULN)
* Cardiac: Left ventricular ejection fraction (LVEF) ≥ 35%
* Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17 year olds)


* Pediatric or adult (ages 0-76 years) HCT recipients
* Suspected high risk GVHD
* Voluntary written consent (adult or parent/guardian with minor assent for 12 through 17 year olds)

Exclusion Criteria

* Progressive malignancy
* Diagnosis of a hormone responsive malignancy
* Uncontrolled infection at initiation of protocol treatment
* Current thromboembolic disease requiring full-dose anticoagulation - patients receiving pharmacologic prophylaxis for thromboembolic disease will be eligible
* Active or recent (within prior 3 months) thrombus, irrespective of anticoagulation status
* Pregnancy as assessed on baseline blood hCG level
* Unwilling or unable to stop supplemental sex hormone therapy (estrogen, progesterone, and/or testosterone preparations)
* Women or men of childbearing potential unwilling to take adequate precautions to avoid pregnancy from the start of protocol treatment through 28 days after the last treatment
Maximum Eligible Age

76 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shernan Holtan, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

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Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Countries

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United States

References

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Holtan SG, Hoeschen A, Cao Q, Ustun C, Betts BC, Jurdi NE, Maakaron J, Rashidi A, Miller JS, Wagner JE, Blazar BR, Jacobson PA, Panoskaltsis-Mortari A, Weisdorf DJ, MacMillan ML. Phase II, Open-Label Clinical Trial of Urinary-Derived Human Chorionic Gonadotropin/Epidermal Growth Factor for Life-Threatening Acute Graft-versus-Host Disease. Transplant Cell Ther. 2023 Aug;29(8):509.e1-509.e8. doi: 10.1016/j.jtct.2023.05.021. Epub 2023 Jun 4.

Reference Type DERIVED
PMID: 37279855 (View on PubMed)

Holtan SG, Hoeschen AL, Cao Q, Arora M, Bachanova V, Brunstein CG, Miller JS, Rashidi A, Slungaard A, Ustun C, Vercellotti GM, Warlick ED, Betts BC, El Jurdi N, He F, Chen C, Gandhi I, Wagner JE, Blazar BR, Jacobson PA, Shabaneh A, Wang J, Panoskaltsis-Mortari A, MacMillan ML, Weisdorf DJ. Facilitating resolution of life-threatening acute GVHD with human chorionic gonadotropin and epidermal growth factor. Blood Adv. 2020 Apr 14;4(7):1284-1295. doi: 10.1182/bloodadvances.2019001259.

Reference Type DERIVED
PMID: 32236525 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2015-02022

Identifier Type: REGISTRY

Identifier Source: secondary_id

2014LS020

Identifier Type: -

Identifier Source: org_study_id