Trial Outcomes & Findings for Autologous Transplant in HIV Patients (BMT CTN 0803) (NCT NCT01141712)

NCT ID: NCT01141712

Last Updated: 2023-01-04

Results Overview

Assess the OS after autologous hematopoietic stem cell transplantation (HCT) for chemotherapy-sensitive aggressive B cell lymphoma or Hodgkin's lymphoma in patients with HIV using BEAM for pre-transplant conditioning. The primary analysis will consist of estimating the 1 year OS probability from the time of transplantation based on the Kaplan-Meier product limit estimator. The 1 year and 2 year OS and confidence interval will be calculated.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 43 participants
• Primary outcome timeframe: Year 1 and 2
• Results posted on: 2023-01-04

Participant Flow

Participants were enrolled between April 2010 and March 2013 from 16 different transplant centers.

Three patients did not undergo transplantation due to disease progression prior to conditioning.

Participant milestones

Measure	Autologous Transplant Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 twice a day from Days -5 to -2, Cytarabine 100 mg/m\^2 twice a day from Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Overall Study STARTED	43
Overall Study COMPLETED	40
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Autologous Transplant Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 twice a day from Days -5 to -2, Cytarabine 100 mg/m\^2 twice a day from Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Overall Study Disease progression	3

Baseline Characteristics

Autologous Transplant in HIV Patients (BMT CTN 0803)

Baseline characteristics by cohort

Measure	Autologous Transplant n=40 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 twice a day (BID) on Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Age, Continuous	46.9 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	13 participants n=5 Participants
Race/Ethnicity, Customized White	24 participants n=5 Participants
Race/Ethnicity, Customized Unknown	3 participants n=5 Participants
Karnofsky Performance Score 100	11 participants n=5 Participants
Karnofsky Performance Score 90	20 participants n=5 Participants
Karnofsky Performance Score 80	7 participants n=5 Participants
Karnofsky Performance Score 70	2 participants n=5 Participants
Participant Diagnosis Hodgkin's Lymphoma	15 participants n=5 Participants
Participant Diagnosis Diffuse Large B-cell Lymphoma	16 participants n=5 Participants
Participant Diagnosis Plasmablastic Lymphoma	2 participants n=5 Participants
Participant Diagnosis Burkitt's Lymphoma	7 participants n=5 Participants
Disease Status Complete Remission	30 participants n=5 Participants
Disease Status Partial Remission	9 participants n=5 Participants
Disease Status Relapsed or Progressive Disease	1 participants n=5 Participants

PRIMARY outcome

Timeframe: Year 1 and 2

Assess the OS after autologous hematopoietic stem cell transplantation (HCT) for chemotherapy-sensitive aggressive B cell lymphoma or Hodgkin's lymphoma in patients with HIV using BEAM for pre-transplant conditioning. The primary analysis will consist of estimating the 1 year OS probability from the time of transplantation based on the Kaplan-Meier product limit estimator. The 1 year and 2 year OS and confidence interval will be calculated.

Outcome measures

Measure	Autologous Transplant n=40 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Overall Survival (OS) 1 year	87.3 percentage of participants Interval 72.1 to 94.5
Overall Survival (OS) 2 years	82 percentage of participants Interval 65.9 to 91.0

SECONDARY outcome

Timeframe: Year 2

Relapse is defined as the appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size. Progression is defined as a lymph node with a diameter of the short axis of less than 1.0 cm must increase by >= 50% and to a size of 1.5 x 1.5 cm or more than 1.5 cm in the long axis.

Outcome measures

Measure	Autologous Transplant n=40 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Relapse/Progression	12.5 percentage of participants Interval 4.5 to 24.8

SECONDARY outcome

Timeframe: Year 2

The time to this event is the time from enrollment until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up, whichever comes first. Progression-free survival (PFS) will be estimated using the Kaplan Meier product limit estimator. The PFS probability and confidence interval will be calculated at two years post-transplant.

Outcome measures

Measure	Autologous Transplant n=40 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Progression-Free Survival (PFS)	79.8 percentage of participants Interval 63.7 to 89.4

SECONDARY outcome

Timeframe: Day 100

Population: One participant died at day 64 and was not included in analysis

The frequencies and proportions of patients who have a CR or PR. CR is defined as the disappearance of all evidence of disease, and PR is defined as the regression of measurable disease and no new sites.

Outcome measures

Measure	Autologous Transplant n=39 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Complete Remission (CR) and/or Partial Response (PR) CR	36 participants
Complete Remission (CR) and/or Partial Response (PR) PR	1 participants
Complete Remission (CR) and/or Partial Response (PR) Relapse/Progression	2 participants

SECONDARY outcome

Timeframe: Year 2

Population: No data collected to analyze this outcome measure

This will be assessed in patients with CR. Patients are considered failure for this end point if they relapse after complete remission. Surviving patients with no history of relapse/progression are censored at time of last follow-up.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Year 2

Population: No data collected to analyze this outcome measure.

This will be assessed in patients with CR. Patients are considered failure for this end point if they die or if they relapse after complete remission. Patients with no history of relapse or death after complete remission are censored at time of last follow up.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 28

Neutrophil recovery is defined as two consecutive days of absolute neutrophil count (ANC) > 500 neutrophils/μL following the expected nadir.

Outcome measures

Measure	Autologous Transplant n=40 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Cumulative Incidence of Neutrophil Recovery	97.5 percentage of participants Interval 77.7 to 99.7

SECONDARY outcome

Timeframe: Day 100

Platelet recovery is defined as a platelet count greater than 20,000/μL for the first of two consecutive labs with no platelet transfusions 7 days prior.

Outcome measures

Measure	Autologous Transplant n=40 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Cumulative Incidence of Platelet Recovery	92.5 percentage of participants Interval 75.9 to 97.8

SECONDARY outcome

Timeframe: Days 100 and 365

Hematologic function will be defined as ANC > 1500 neutrophils/μL, Hemoglobin> 10g/dL without transfusion support, and platelets > 100,000/μL

Outcome measures

Measure	Autologous Transplant n=40 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Hematologic Function Day 100	11 participants
Hematologic Function Day 365	23 participants

SECONDARY outcome

Timeframe: Year 2

Toxicities will be defined by using the version 3.0 NCI Common Terminology Criteria for Adverse Events (CTCAE) criteria. Only grade 3 and higher toxicities will be collected.

Outcome measures

Measure	Autologous Transplant n=40 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Number of Participants Experiencing Toxicity	9 participants

SECONDARY outcome

Timeframe: Year 1

Microbiologically documented infections will be reported by site of disease, date of onset, severity, and resolution, if any.

Outcome measures

Measure	Autologous Transplant n=40 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Number of Participants Experiencing Infections	22 participants

SECONDARY outcome

Timeframe: Day 100

TRM is defined as death occurring in a patient from causes other than relapse or progression. A cumulative incidence curve will be computed along with a 95% confidence interval at 100 days post-transplant.

Outcome measures

Measure	Autologous Transplant n=40 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Treatment-Related Mortality (TRM)	5.2 percentage of participants Interval 0.9 to 15.2

SECONDARY outcome

Timeframe: Year 1

Immunologic Reconstitution will be assessed by quantitative immunoglobulin measurement (IgM, IgG and IgA)

Outcome measures

Measure	Autologous Transplant n=40 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Immunologic Reconstitution IgG	1090 mg/dL Interval 270.0 to 2331.0
Immunologic Reconstitution IgA	123 mg/dL Interval 6.0 to 534.0
Immunologic Reconstitution IgM	48.5 mg/dL Interval 24.0 to 254.0

SECONDARY outcome

Timeframe: Baseline, Days 100, 180, 365, and 730

Population: Participants with an undetectable (\<50 copies/mL) viral load are not included in this analysis (Baseline = 32, Day 100 = 19, Day 180 = 20, Day 365 = 19, and Day 730 = 21)

HIV RNA assay will be performed at the specified time points and summarize the assessments of the viral copy number using descriptive statistics.

Outcome measures

Measure	Autologous Transplant n=32 Participants Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
HIV Single-Copy Polymerase Chain Reaction (PCR) Day 365	97 copies/mL Interval 75.0 to 5097.0
HIV Single-Copy Polymerase Chain Reaction (PCR) Baseline	80 copies/mL Interval 50.0 to 17455.0
HIV Single-Copy Polymerase Chain Reaction (PCR) Day 100	298 copies/mL Interval 58.0 to 1100.0
HIV Single-Copy Polymerase Chain Reaction (PCR) Day 180	84 copies/mL Interval 55.0 to 36815.0
HIV Single-Copy Polymerase Chain Reaction (PCR) Day 730	130 copies/mL Interval 75.0 to 351.0

SECONDARY outcome

Timeframe: Day 30 and 100

Population: No data collected to analyze this outcome measure.

Level of microbial translocation markers will be determined by nonparametric Mann-Whitney tests comparing the distribution of prior microbial translocation markers between patients.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 100, 180, and 365

Population: No data collected to analyze this outcome measure.

The presence of clonal Ig DNA in plasma will be assessed, as will EBV copy number in plasma and in peripheral blood

Outcome measures

Outcome data not reported

Adverse Events

Autologous Transplant

Serious events: 6 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Autologous Transplant n=40 participants at risk Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Blood and lymphatic system disorders Febrile neutropenia	2.5% 1/40 • Number of events 1 • 2 years post-transplant Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grades 3-5 adverse events were required to be reported through the AE system per protocol.
Cardiac disorders Angina pectoris	2.5% 1/40 • Number of events 1 • 2 years post-transplant Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grades 3-5 adverse events were required to be reported through the AE system per protocol.
Gastrointestinal disorders Odynophagia	2.5% 1/40 • Number of events 1 • 2 years post-transplant Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grades 3-5 adverse events were required to be reported through the AE system per protocol.
Infections and infestations Septic shock	2.5% 1/40 • Number of events 1 • 2 years post-transplant Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grades 3-5 adverse events were required to be reported through the AE system per protocol.
Vascular disorders Deep vein thrombosis	5.0% 2/40 • Number of events 2 • 2 years post-transplant Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grades 3-5 adverse events were required to be reported through the AE system per protocol.

Other adverse events

Measure	Autologous Transplant n=40 participants at risk Patients will receive BCNU 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 BID Days -5 to -2, Cytarabine 100 mg/m\^2 BID Days -5 to -2, and Melphalan 140 mg/m\^2 Day -1 followed by autologous HCT.
Infections and infestations Appendicitis	2.5% 1/40 • Number of events 1 • 2 years post-transplant Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grades 3-5 adverse events were required to be reported through the AE system per protocol.
Metabolism and nutrition disorders Hyperglycaemia	2.5% 1/40 • Number of events 1 • 2 years post-transplant Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grades 3-5 adverse events were required to be reported through the AE system per protocol.
Metabolism and nutrition disorders Hypernatraemia	2.5% 1/40 • Number of events 1 • 2 years post-transplant Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grades 3-5 adverse events were required to be reported through the AE system per protocol.

Additional Information

Adam Mendizabal, PhD

The Emmes Corporation

Phone: 301-251-1161

Email: amendizabal@emmes.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place