Autologous Transplant in HIV Patients (BMT CTN 0803)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Blood and Marrow Transplant Clinical Trials Network
Information provided by (Responsible Party):
Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01141712
First received: June 9, 2010
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Lymphoma
HIV
Procedure: Autologous transplant
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: High Dose Chemotherapy With Autologous Stem Cell Rescue for Aggressive B Cell Lymphoma and Hodgkin Lymphoma in HIV-infected Patients (BMT CTN 0803)

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Assess the overall survival 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


Secondary Outcome Measures:
  • Time to progression [ Time Frame: The time to this event is measured from transplant. ] [ Designated as safety issue: Yes ]
    The event is relapse/progression or receiving anti-lymphoma therapy, other than post-transplant consolidative localized radiation (maximum 3 sites) to sites of prior bulk disease pre-transplant (greater than 3cm). Deaths without relapse/progression are considered as a competing risk. Surviving patients with no history of relapse/progression are censored at time of last follow-up.

  • Progression-free survival [ Time Frame: The time to this event is the time from transplant until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up, whichever comes first. ] [ Designated as safety issue: Yes ]
    Patients are considered a failure for this endpoint if they die or if they relapse/progress or receive anti-lymphoma therapy, other than post-transplant consolidative localized radiation (maximum 3 sites) to sites of prior bulk disease pre-transplant (greater than 3cm).

  • CR and CR+PR proportion [ Time Frame: Assessed at Day 100 ] [ Designated as safety issue: Yes ]
    Complete response (CR) and/or complete response plus partial response

  • Time to progression after CR [ Time Frame: The time to this event is measured from documentation of complete response for patients entering the trial in PR and from enrollment for patients entering the trial in CR. ] [ Designated as safety issue: Yes ]
    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.

  • Lymphoma disease-free survival [ Time Frame: The time to this event is measured from documentation of complete response for patients enrolling in PR and from enrollment for patients entering the trial in CR. ] [ Designated as safety issue: Yes ]
    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.

  • Time to hematopoietic recovery [ Time Frame: Two consecutive days; two consecutive labs ] [ Designated as safety issue: Yes ]
    Time to neutrophil recovery will be the first of two consecutive days of greater than 500 neutrophils/μL following the expected nadir. Time to platelet engraftment will be the date platelet count is greater than 20,000/μL for the first of two consecutive labs with no platelet transfusions 7 days prior.

  • Hematologic function at Day 100 [ Time Frame: Assessed at days 100 and 365 ] [ Designated as safety issue: Yes ]
    Hematologic function will be defined by ANC greater than 1500, Hemoglobin greater than 10g/dL without transfusion support, and platelets greater than 100,000 and measured at Day 100 and 1 year. Use of growth factors will be noted.

  • Toxicities [ Time Frame: Assessed at days 28, 56, 100, 180, 365, and 730 ] [ Designated as safety issue: Yes ]
    Toxicities will be defined by using the version 3.0 NCI CTCAE criteria. Only grade 3 and higher toxicities will be collected.

  • Incidence of infections [ Time Frame: Date of transplant through one year post-transplant ] [ Designated as safety issue: Yes ]
    Microbiologically documented infections will be reported by site of disease, date of onset, severity, and resolution, if any.

  • Treatment-related mortality [ Time Frame: Assessed at day 100 ] [ Designated as safety issue: Yes ]
    Treatment-Related Mortality (TRM) is defined as death occurring in a patient from causes other than relapse or progression.

  • Immunologic reconstitution [ Time Frame: Studies will be performed at days 60, 180, and 365 post-transplant. ] [ Designated as safety issue: Yes ]
    Immune reconstitution assays on peripheral blood will include (1) immunophenotypic analysis of both T and natural killer subsets; (2) functional evaluation of adaptive and innate immune responsiveness; and (3) quantitative immunoglobulin measurement (IgM, IgG and IgA). Quantitative immunoglobulin measurements (IgM, IgG and IgA) will also be performed prior to initiation of conditioning. These will be summarized at each time point using descriptive statistics.

  • HIV Single-Copy PCR [ Time Frame: HIV RNA within 90 days prior to start of conditioning, at Day 100, 180, and 1 year post transplant will be measured. ] [ Designated as safety issue: No ]
    For those patients with no detectable viral RNA in their baseline sample using the standard clinical test performed at the clinical site, additional blood samples will be collected at two time points prior to the initiation of ablative chemotherapy (at 2 time points) and at Days 180, 365 and 730 post-transplant. Plasma aliquots from these time points will be sent for further analysis at a project laboratory for possible low-level HIV-1 viremia by a sensitive single-copy PCR assay (capable of detecting HIV-1 RNA levels down to 1 copy per milliliter of plasma).

  • Microbial translocation markers [ Time Frame: 1 week prior to conditioning, day -3, and days 14 and 100 after infusion ] [ Designated as safety issue: No ]
    Blood specimens for microbial translocation will be collected within 1 week prior to the initiation of conditioning, on Day -3 of conditioning and Days 7, 14 and 100 after stem cell infusion.

  • Ig and EBV DNA in Blood [ Time Frame: 1 week prior to conditioning, day -3, day 100, day 180 and day 365 ] [ Designated as safety issue: No ]
    Blood specimens will be collected within 1 week prior to the initiation of conditioning, on Day -3 of conditioning and at 100 days, 6 months and 1 year. The presence of clonal Ig DNA in plasma will be assessed, as will EBV copy number in plasma and in PBMC at each of these time points.


Estimated Enrollment: 40
Study Start Date: February 2011
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Procedure: 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.

Detailed Description:

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 BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m2 BID 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 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).

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of persistent or recurrent 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 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 ALT and 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: DLCO, FEV1, 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 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 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 MDS/AML or abnormal cytogenetic analysis indicative of MDS on the pre-transplant bone marrow examination. Pathology report documentation need not be submitted.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01141712

Locations
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010-3000
University of California San Diego Medical Center
La Jolla, California, United States, 92093
UCLA, Center for Clinical AIDS Research and Education
Los Angeles, California, United States, 90035
United States, Florida
University of Florida College of Medicine
Gainesville, Florida, United States, 32610
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33624
United States, Georgia
BMT Program at Northside Hospital
Atlanta, Georgia, United States, 30342
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Maryland
Johns Hopkins Medical Institution
Baltimore, Maryland, United States, 21231
University of Maryland Medical Systems, Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, Missouri
University of Washington, Barnes Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10065
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10174
University of Rochester
Rochester, New York, United States, 14642
United States, Ohio
University Hospitals of Cleveland
Cleveland, Ohio, United States, 44106-5061
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Texas
University of Texas, MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Sponsors and Collaborators
Medical College of Wisconsin
Blood and Marrow Transplant Clinical Trials Network
Investigators
Study Chair: Joseph Alvarnas, MD City of Hope National Medical Center
Study Chair: Richard Ambinder, MD Johns Hopkins Medical Institution
  More Information

Additional Information:
No publications provided

Responsible Party: Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01141712     History of Changes
Other Study ID Numbers: 698, U01HL069294, U01HL069294-06, BMT CTN 0803
Study First Received: June 9, 2010
Last Updated: June 2, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Medical College of Wisconsin:
HIV
B-cell Lymphoma
Burkitt's Lymphoma
Follicular Lymphoma
Hodgkin's Lymphoma

Additional relevant MeSH terms:
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 29, 2014