Autologous Transplant in HIV Patients (BMT CTN 0803)

NCT ID: NCT01141712

Last Updated: 2023-01-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-04-30

Study Completion Date

2016-06-30

Brief Summary

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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.

Detailed Description

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BACKGROUND:

Non-Hodgkin lymphoma (NHL) is an AIDS-defining diagnosis for patients infected with the Human Immunodeficiency Virus (HIV). While the incidence of NHL has decreased amongst HIV-infected patients since the advent of highly-active anti-retroviral therapy (HAART), lymphoma remains a significant cause of death for this patient population. The prognosis for patients with AIDS-related lymphoma is dramatically different in the era of HAART therapy. In a comparison of treatment outcomes for patients treated before and after the advent of HAART, there is a statistically significant improvement in the overall survival of patients treated with HAART. Unfortunately, despite considerable advances in the treatment of AIDS-related NHL, induction-failure and disease relapse remain key challenges. The prognosis for patients with refractory and relapsed NHL is poor with overall survival rates of less than 20 percent for patients treated with non-transplant salvage therapies. Based upon a randomized trial and numerous phase II trials, high-dose therapy with autologous hematopoietic cell transplantation (HCT) has been established as the standard of care for patients with chemotherapy-sensitive relapsed non-Hodgkin lymphoma.

DESIGN NARRATIVE:

All patients must have chemosensitive disease as demonstrated by response to induction or salvage chemotherapy. Patients must also have less than or equal to 10percent bone marrow involvement after their most recent salvage therapy. Patients cannot have had prior autologous or allogeneic HCT. Patients must initiate conditioning therapy within 3 months of mobilization or bone marrow harvest.

Mobilization therapy may be employed per institutional guidelines. Patients must have an adequate autograft to be eligible for the protocol. Patients may not have HIV refractory to pharmacologic therapy. Patients must not have opportunistic infection that is not responding to therapy. Patients will receive Carmustine (BCNU) 300 mg/m\^2 Day -6, Etoposide 100 mg/m\^2 twice a day (BID) on Days -5 to -2, Cytarabine 100 mg/m2 BID on Days -5 to -2, and Melphalan 140 mg/m2 Day -1 followed by autologous HCT.

Patients will be followed for 2 years post-transplant. Survival data, time to progression data, progression-free survival data, time to progression after Complete Remission (CR) data, lymphoma disease-free survival data, time to hematopoietic recovery data, hematologic function data, toxicity data, incidence of infections, treatment-related mortality data, immunologic reconstitution data, data assessing the impact of therapy on the HIV reservoir and microbial gut translocation will be recorded and reported periodically to the BMT CTN Data and Coordinating Center (DCC).

Conditions

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Lymphoma HIV

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Autologous transplant

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.

Group Type OTHER

Autologous transplant

Intervention Type PROCEDURE

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

BCNU

Intervention Type DRUG

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

Etoposide

Intervention Type DRUG

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

Cytarabine

Intervention Type DRUG

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

Melphalan

Intervention Type DRUG

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

Interventions

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Autologous transplant

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

Intervention Type PROCEDURE

BCNU

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

Intervention Type DRUG

Etoposide

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

Intervention Type DRUG

Cytarabine

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

Intervention Type DRUG

Melphalan

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

Intervention Type DRUG

Other Intervention Names

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Carmustine VP-16 Depocyt Alkeran

Eligibility Criteria

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Inclusion Criteria

* 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.
* 15 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

15 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Blood and Marrow Transplant Clinical Trials Network

NETWORK

Sponsor Role collaborator

National Marrow Donor Program

OTHER

Sponsor Role collaborator

Medical College of Wisconsin

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mary Horowitz, MD

Role: STUDY_DIRECTOR

Center for International Blood and Marrow Transplant Research

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status

University of California San Diego Medical Center

La Jolla, California, United States

Site Status

UCLA

Los Angeles, California, United States

Site Status

University of CA, SF

San Francisco, California, United States

Site Status

University of Florida College of Medicine

Gainesville, Florida, United States

Site Status

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

BMT Program at Northside Hospital

Atlanta, Georgia, United States

Site Status

University of Maryland Medical Systems, Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins Medical Institution

Baltimore, Maryland, United States

Site Status

Washington University/Barnes Jewish Hospital

St Louis, Missouri, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Ohio State University Medical Center

Columbus, Ohio, United States

Site Status

University of Texas/MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type RESULT
PMID: 27297790 (View on PubMed)

Provided Documents

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Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

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U01HL069294

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01HL069294-06

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA121947

Identifier Type: NIH

Identifier Source: secondary_id

View Link

BMTCTN0803

Identifier Type: -

Identifier Source: org_study_id

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