Autologous Transplant in HIV Patients (BMT CTN 0803)
- Conditions
- Interventions
- Registration Number
- NCT01141712
- Lead Sponsor
- Medical College of Wisconsin
- 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.
- Detailed Description
BACKGROUND:
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Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 43
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Autologous transplant 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. Autologous transplant BCNU 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. Autologous transplant Cytarabine 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. Autologous transplant Etoposide 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. Autologous transplant Melphalan 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 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 l...
- Secondary Outcome Measures
Name Time Method Relapse/Progression 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.
Progression-Free Survival (PFS) 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.
Complete Remission (CR) and/or Partial Response (PR) Day 100 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.
Time to Progression After CR Year 2 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 Year 2 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.
Cumulative Incidence of Neutrophil Recovery Day 28 Neutrophil recovery is defined as two consecutive days of absolute neutrophil count (ANC) \> 500 neutrophils/μL following the expected nadir.
Number of Participants Experiencing Toxicity 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.
Number of Participants Experiencing Infections Year 1 Microbiologically documented infections will be reported by site of disease, date of onset, severity, and resolution, if any.
Cumulative Incidence of Platelet Recovery 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.
Hematologic Function 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
Treatment-Related Mortality (TRM) 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.
Immunologic Reconstitution Year 1 Immunologic Reconstitution will be assessed by quantitative immunoglobulin measurement (IgM, IgG and IgA)
HIV Single-Copy Polymerase Chain Reaction (PCR) Baseline, Days 100, 180, 365, and 730 HIV RNA assay will be performed at the specified time points and summarize the assessments of the viral copy number using descriptive statistics.
Microbial Translocation Markers Day 30 and 100 Level of microbial translocation markers will be determined by nonparametric Mann-Whitney tests comparing the distribution of prior microbial translocation markers between patients.
Ig and Epstein-Barr Virus (EBV) DNA in Blood Day 100, 180, and 365 The presence of clonal Ig DNA in plasma will be assessed, as will EBV copy number in plasma and in peripheral blood
Trial Locations
- Locations (16)
University of Rochester
🇺🇸Rochester, New York, United States
University of CA, SF
🇺🇸San Francisco, California, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
University of Maryland Medical Systems, Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
University of California San Diego Medical Center
🇺🇸La Jolla, California, United States
UCLA
🇺🇸Los Angeles, California, United States
University of Florida College of Medicine
🇺🇸Gainesville, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
BMT Program at Northside Hospital
🇺🇸Atlanta, Georgia, United States
Johns Hopkins Medical Institution
🇺🇸Baltimore, Maryland, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Washington University/Barnes Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
University of Texas/MD Anderson Cancer Center
🇺🇸Houston, Texas, United States