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.
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).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
43
Participants will receive the BEAM conditioning regimen followed by autologous HCT.
Participants will receive BCNU 300 mg/m\^2 Day -6
Participants will receive Etoposide 100 mg/m\^2 BID Days -5 to -2
City of Hope National Medical Center
Duarte, California, United States
University of California San Diego Medical Center
La Jolla, California, United States
Overall Survival (OS)
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.
Time frame: Year 1 and 2
Relapse/Progression
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.
Time frame: Year 2
Progression-Free Survival (PFS)
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.
Time frame: Year 2
Complete Remission (CR) and/or Partial Response (PR)
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 frame: Day 100
Time to Progression After CR
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.
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Participants will receive Cytarabine 100 mg/m\^2 BID Days -5 to -2
Participants will receive Melphalan 140 mg/m\^2 Day -1
UCLA
Los Angeles, California, United States
University of CA, SF
San Francisco, California, United States
University of Florida College of Medicine
Gainesville, Florida, United States
H. Lee Moffitt Cancer Center
Tampa, Florida, United States
Emory University
Atlanta, Georgia, United States
BMT Program at Northside Hospital
Atlanta, Georgia, United States
University of Maryland Medical Systems, Greenebaum Cancer Center
Baltimore, Maryland, United States
Johns Hopkins Medical Institution
Baltimore, Maryland, United States
...and 6 more locations
Time frame: Year 2
Lymphoma Disease-free Survival
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 frame: Year 2
Cumulative Incidence of Neutrophil Recovery
Neutrophil recovery is defined as two consecutive days of absolute neutrophil count (ANC) \> 500 neutrophils/μL following the expected nadir.
Time frame: Day 28
Cumulative Incidence of Platelet Recovery
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.
Time frame: Day 100
Hematologic Function
Hematologic function will be defined as ANC \> 1500 neutrophils/μL, Hemoglobin\> 10g/dL without transfusion support, and platelets \> 100,000/μL
Time frame: Days 100 and 365
Number of Participants Experiencing Toxicity
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.
Time frame: Year 2
Number of Participants Experiencing Infections
Microbiologically documented infections will be reported by site of disease, date of onset, severity, and resolution, if any.
Time frame: Year 1
Treatment-Related Mortality (TRM)
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.
Time frame: Day 100
Immunologic Reconstitution
Immunologic Reconstitution will be assessed by quantitative immunoglobulin measurement (IgM, IgG and IgA)
Time frame: Year 1
HIV Single-Copy Polymerase Chain Reaction (PCR)
HIV RNA assay will be performed at the specified time points and summarize the assessments of the viral copy number using descriptive statistics.
Time frame: Baseline, Days 100, 180, 365, and 730
Microbial Translocation Markers
Level of microbial translocation markers will be determined by nonparametric Mann-Whitney tests comparing the distribution of prior microbial translocation markers between patients.
Time frame: Day 30 and 100
Ig and Epstein-Barr Virus (EBV) DNA in Blood
The presence of clonal Ig DNA in plasma will be assessed, as will EBV copy number in plasma and in peripheral blood
Time frame: Day 100, 180, and 365