Autologous Transplant in HIV Patients (BMT CTN 0803)

NCT01141712 | Completed Phase 2 Results DMC

• 4 other identifiers: BMTCTN0803U01HL069294U01HL069294-06U01CA121947
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 16

Brief Summary

This study is a Phase II, multicenter trial assessing overall survival after autologous hematopoietic stem cell transplantation using a BEAM transplant regimen (carmustine, etoposide, cytarabine, melphalan) in lymphoma patients with HIV.

Conditions

Lymphoma; HIV

Keywords

HIV; B-cell Lymphoma; Burkitt's Lymphoma; Follicular Lymphoma; Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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.

  Year 1 and 2

Secondary Outcomes (15)

• Relapse/Progression

  Year 2

• Progression-Free Survival (PFS)

  Year 2

• Complete Remission (CR) and/or Partial Response (PR)

  Day 100

• Time to Progression After CR

  Year 2

• Lymphoma Disease-free Survival

  Year 2

Study Arms (1)

Autologous transplant

OTHER

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.

Procedure: Autologous transplant; Drug: BCNU; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan

Interventions

Autologous transplant PROCEDURE

Participants will receive the BEAM conditioning regimen followed by autologous HCT.

Autologous transplant

BCNU DRUG

Participants will receive BCNU 300 mg/m\^2 Day -6

Also known as: Carmustine

Autologous transplant

Etoposide DRUG

Participants will receive Etoposide 100 mg/m\^2 BID Days -5 to -2

Also known as: VP-16

Autologous transplant

Cytarabine DRUG

Participants will receive Cytarabine 100 mg/m\^2 BID Days -5 to -2

Also known as: Depocyt

Autologous transplant

Melphalan DRUG

Participants will receive Melphalan 140 mg/m\^2 Day -1

Also known as: Alkeran

Autologous transplant

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of persistent or recurrent World Health Organization (WHO) classification diffuse large B-cell lymphoma, composite lymphoma with \> 50% diffuse large B-cell lymphoma, mediastinal B-cell lymphoma, immunoblastic, plasmablastic, Burkitt's or Burkitt-like or classical Hodgkin's lymphoma. Patients transformed from follicular lymphoma are eligible for the study, pending fulfillment of other criteria.
• years old or older
• Three or fewer prior regimens of chemotherapy over the entire course of their disease treatment (including one induction chemotherapy and no more than 2 salvage chemotherapies). Monoclonal antibody therapy and involved field radiation therapy will not be counted as prior therapies.
• All patients must have chemosensitive disease as demonstrated by at least a partial response to induction or salvage therapy.
• Less than or equal to 10% bone marrow involvement.
• Patients with adequate organ function as measured by: a)Cardiac: American Heart Association Class I: Patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain. Additionally, all patients must have a left ventricular ejection fraction at rest greater than or equal to 40% demonstrated by Multi Gated Acquisition Scan (MUGA) or echocardiogram; b)Hepatic: (i) Bilirubin less than 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome or antiretroviral therapy) and alanine transaminase (ALT) and aspartate transaminase (AST) greater than 3x the upper limit of normal; (ii) Concomitant Hepatitis: Patients with chronic hepatitis B or C may be enrolled on the trial providing the above criteria are met. In addition, no active viral replication - undetectable (viral load less than 500 copies/ml) hepatitis B DNA level by PCR and no clinical or pathologic evidence of irreversible chronic liver disease; c)Renal: Creatinine clearance (calculated creatinine clearance is permitted) greater than 40 mL/min; d)Pulmonary: Carbon Monoxide Diffusing Capacity (DLCO), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) greater than or equal to 45% of predicted (corrected for hemoglobin).
• Autologous peripheral stem cell graft with a minimum of greater than or less than 1.5 x 10\^6 CD 34+ cells/kg (target greater than or less than 2.0 x 10\^6 CD 34+ cells/kg) or if peripheral blood stem cell (PBSC) mobilization fails, cells can be obtained by bone marrow harvest per institutional practices (in cases where bone marrow will be used for transplantation, the required CD34+ dose does not apply and institutional requirements for total nucleated cell dose should apply).
• Initiate conditioning therapy within 3 months of mobilization or bone marrow harvest.
• Signed informed consent.
• Patients on antiretroviral therapies (ARVs) can either have: a) Undetectable HIV viral load (VL less than 50 copies); b) If VL detectable at less than 2000 copies/mL must have review of previous antiretroviral regimens or previous genotypic or phenotypic testing which indicate the ability to fully suppress virus by addition of sensitive drugs. This review will be carried out by the Infectious Disease (ID) specialist caring for the patient; c)If VL detectable at greater than 2000 copies/mL, a current HIV genotype and/or phenotype must be obtained. If a HAART regimen to which the patient's virus is sensitive can be determined based on genotype and previous antiretroviral experience, then the patient will be considered eligible in this regard. This review will be carried out by the ID specialist caring for the patient.

You may not qualify if:

• Karnofsky performance score less than 70%.
• Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement).
• Prior malignancy in the 5 years prior to enrollment except resected basal cell carcinoma, treated cervical carcinoma in situ or Kaposi's sarcoma: a)Symptomatic Kaposi's sarcoma currently requiring therapy is excluded (patients receiving topical therapy for minimal disease are not included in this definition); b)Prior treatment with topical agents, local radiation, or up to 6 cycles of cytotoxic chemotherapy at least six months prior is permitted; c) Other cancers treated with curative intent less than 5 years previously will not be allowed unless approved by the Medical Monitor or Protocol Chair; d)Cancer treated with curative intent more than 5 years previously will be allowed.
• Pregnant (positive β-HCG) or breastfeeding.
• Fertile men or women unwilling to use contraceptive techniques from the time of initiation of mobilization until six-months post-transplant.
• Prior autologous or allogeneic HCT.
• Patients with evidence of Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) or abnormal cytogenetic analysis indicative of MDS on the pre-transplant bone marrow examination. Pathology report documentation need not be submitted.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator
• Blood and Marrow Transplant Clinical Trials Network: collaborator
• National Marrow Donor Program: collaborator

Study Sites (16)

City of Hope National Medical Center

Duarte, California, 91010-3000, United States

Location

University of California San Diego Medical Center

La Jolla, California, 92093, United States

Location

UCLA

Los Angeles, California, 90035, United States

Location

University of CA, SF

San Francisco, California, 94143, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33624, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

BMT Program at Northside Hospital

Atlanta, Georgia, 30342, United States

Location

University of Maryland Medical Systems, Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Medical Institution

Baltimore, Maryland, 21231, United States

Location

Washington University/Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10174, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

University of Texas/MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Alvarnas JC, Le Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016 Aug 25;128(8):1050-8. doi: 10.1182/blood-2015-08-664706. Epub 2016 Jun 13.

  PMID: 27297790 RESULT

MeSH Terms

Conditions

Lymphoma; Lymphoma, B-Cell; Burkitt Lymphoma; Lymphoma, Follicular; Hodgkin Disease

Interventions

Transplantation, Autologous; Carmustine; Etoposide; Cytarabine; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Transplantation; Surgical Procedures, Operative; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Adam Mendizabal, PhD
• Organization: The Emmes Corporation

amendizabal@emmes.com

301-251-1161

Study Officials

• Mary Horowitz, MD

  Center for International Blood and Marrow Transplant Research

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2010
• First Posted: June 10, 2010
• Study Start: April 1, 2010
• Primary Completion: May 1, 2015
• Study Completion: June 1, 2016
• Last Updated: January 4, 2023
• Results First Posted: March 28, 2017

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: Within 6 months of official study closure at participating sites.
• Access Criteria: Available to the public.

Locations

US (16)