Autologous Transplant in HIV Patients (BMT CTN 0803)
|ClinicalTrials.gov Identifier: NCT01141712|
Recruitment Status : Completed
First Posted : June 10, 2010
Results First Posted : March 28, 2017
Last Update Posted : October 27, 2017
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma HIV||Procedure: Autologous transplant Drug: BCNU Drug: Etoposide Drug: Cytarabine Drug: Melphalan||Phase 2|
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.
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).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||43 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Study Start Date :||April 2010|
|Primary Completion Date :||May 2015|
|Study Completion Date :||June 2016|
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
Participants will receive the BEAM conditioning regimen followed by autologous HCT.Drug: BCNU
Participants will receive BCNU 300 mg/m^2 Day -6
Other Name: CarmustineDrug: Etoposide
Participants will receive Etoposide 100 mg/m^2 BID Days -5 to -2
Other Name: VP-16Drug: Cytarabine
Participants will receive Cytarabine 100 mg/m^2 BID Days -5 to -2
Other Name: DepocytDrug: Melphalan
Participants will receive Melphalan 140 mg/m^2 Day -1
Other Name: Alkeran
- Overall Survival (OS) [ Time Frame: 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 limit estimator. The 1 year and 2 year OS and confidence interval will be calculated.
- Relapse/Progression [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day 28 ]Neutrophil recovery is defined as two consecutive days of absolute neutrophil count (ANC) > 500 neutrophils/μL following the expected nadir.
- Cumulative Incidence of Platelet Recovery [ Time Frame: 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 [ Time Frame: 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
- Number of Participants Experiencing Toxicity [ Time Frame: 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 [ Time Frame: Year 1 ]Microbiologically documented infections will be reported by site of disease, date of onset, severity, and resolution, if any.
- Treatment-Related Mortality (TRM) [ Time Frame: 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 [ Time Frame: Year 1 ]Immunologic Reconstitution will be assessed by quantitative immunoglobulin measurement (IgM, IgG and IgA)
- HIV Single-Copy Polymerase Chain Reaction (PCR) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01141712
|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|
|Los Angeles, California, United States, 90035|
|University of CA, SF|
|San Francisco, California, United States, 94143|
|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|
|Atlanta, Georgia, United States, 30322|
|BMT Program at Northside Hospital|
|Atlanta, Georgia, United States, 30342|
|United States, Maryland|
|University of Maryland Medical Systems, Greenebaum Cancer Center|
|Baltimore, Maryland, United States, 21201|
|Johns Hopkins Medical Institution|
|Baltimore, Maryland, United States, 21231|
|United States, Missouri|
|Washington University/Barnes Jewish Hospital|
|Saint 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|
|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|
|Study Director:||Mary Horowitz, MD||Center for International Blood and Marrow Transplant Research|