Autologous Transplant in HIV Patients (BMT CTN 0803)
This trial is active, not recruiting.
|Sponsor||Medical College of Wisconsin|
|Collaborator||National Heart, Lung, and Blood Institute (NHLBI)|
|Start date||February 2011|
|End date||May 2015|
|Trial size||40 participants|
|Trial identifier||NCT01141712, BMT CTN 0803, BMTCTN0803, U01HL069294, U01HL069294-06|
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.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Duarte, CA||City of Hope National Medical Center||no longer recruiting|
|La Jolla, CA||University of California San Diego Medical Center||no longer recruiting|
|Los Angeles, CA||UCLA, Center for Clinical AIDS Research and Education||no longer recruiting|
|Gainesville, FL||University of Florida College of Medicine||no longer recruiting|
|Tampa, FL||H. Lee Moffitt Cancer Center||no longer recruiting|
|Atlanta, GA||BMT Program at Northside Hospital||no longer recruiting|
|Atlanta, GA||Emory University||no longer recruiting|
|Chicago, IL||Rush University Medical Center||no longer recruiting|
|Baltimore, MD||Johns Hopkins Medical Institution||no longer recruiting|
|Baltimore, MD||University of Maryland Medical Systems, Greenebaum Cancer Center||no longer recruiting|
|St. Louis, MO||University of Washington, Barnes Jewish Hospital||no longer recruiting|
|New York, NY||Memorial Sloan-Kettering Cancer Center||no longer recruiting|
|New York, NY||Weill Cornell Medical College||no longer recruiting|
|Rochester, NY||University of Rochester||no longer recruiting|
|Cleveland, OH||University Hospitals of Cleveland||no longer recruiting|
|Columbus, OH||Ohio State University Medical Center||no longer recruiting|
|Houston, TX||University of Texas, MD Anderson Cancer Center||no longer recruiting|
|Seattle, WA||Fred Hutchinson Cancer Research Center||no longer recruiting|
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
time frame: 1 year
Time to progression
time frame: The time to this event is measured from transplant.
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.
CR and CR+PR proportion
time frame: Assessed at Day 100
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.
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.
Time to hematopoietic recovery
time frame: Two consecutive days; two consecutive labs
Hematologic function at Day 100
time frame: Assessed at days 100 and 365
time frame: Assessed at days 28, 56, 100, 180, 365, and 730
Incidence of infections
time frame: Date of transplant through one year post-transplant
time frame: Assessed at day 100
time frame: Studies will be performed at days 60, 180, and 365 post-transplant.
HIV Single-Copy polymerase chain reaction (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.
Microbial translocation markers
time frame: 1 week prior to conditioning, day -3, and days 14 and 100 after infusion
Ig and Epstein-Barr virus (EBV) DNA in Blood
time frame: 1 week prior to conditioning, day -3, day 100, day 180 and day 365
Male or female participants at least 15 years old.
- 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 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.
|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)|
|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 Carmustine (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).|
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