Allogeneic Transplant in HIV Patients (BMT CTN 0903)
Drug: Fludarabine and Busulfan
Drug: Fludarabine and Melphalan
Drug: Busulfan and Fludarabine
Drug: Cyclophosphamide and Total Body Irradiation
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Allogeneic Hematopoietic Cell Transplant for Hematological Cancers and Myelodysplastic Syndromes in HIV-Infected Individuals (BMT CTN #0903)|
- Non-Relapse Mortality [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]The events for non-relapse mortality are death due to any cause other than relapse of the underlying malignancy
- Disease Status Following Transplant [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]Patients will be assessed for disease status at Day 100 post-HCT: complete remission, partial remission (HL, NHL), stable disease (HL, NHL), relapse.
- Chimerism [ Time Frame: 4 weeks, 100 days and 6 months ] [ Designated as safety issue: Yes ]Blood samples will be evaluated for T cell and myeloid chimerism at 4 weeks, 100 days and 6 months post-transplant.
- 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.
- Six Month Overall Survival [ Time Frame: Six months post transplant ] [ Designated as safety issue: Yes ]Overall survival is defined as time from transplant to death or last follow-up.
- Acute Graft-versus-Host Disease (GVHD) [ Time Frame: 100 Days ] [ Designated as safety issue: Yes ]Acute GVHD will be graded according to the BMT CTN Manual of Procedures. The time to onset of acute grades II-IV GVHD and grades III-IV GVHD will be recorded, as well as the maximum grade achieved.
- Chronic Graft-versus-Host Disease (GVHD) [ Time Frame: 100 days, 6 months, 2 years ] [ Designated as safety issue: Yes ]Chronic GVHD will be scored according to the BMT CTN Manual of Procedures. The time to onset of limited and extensive chronic GVHD will be recorded.
- Immunologic Reconstitution [ Time Frame: 8 Weeks; 6, 12 and 24 Months ] [ Designated as safety issue: Yes ]This will be measured in all patients at 8 weeks, 6 months, 12 months and 24 months post-transplant. Tests to be performed on peripheral blood at those time points include CD2, CD3, CD4, CD8, CD19, CD3+/CD25+, CD45 RA/RO, CD56+/CD3-, and quantitative immunoglobulins (IgM, IgG and IgA).
- Impact of Therapy on the HIV Reservoir [ Time Frame: Day 100, 6 Months, 12 Months, and 24 Months ] [ Designated as safety issue: Yes ]HIV-1 RNA in plasma will be measured by standard real-time reverse transcription polymerase chain reaction (RT-PCR) (detection limit 40 copies/ml) and by the investigational single copy assay (SCA, detection limit 0.38 copy/ml). HIV-1 DNA in peripheral blood mononuclear cells (PBMCs) and other cells will be quantified using the same primers and probes used for SCA but without a reverse transcription step. HIV-1 RNA levels will be measured in plasma prior to the initiation of ablative chemotherapy, and at Day +100, 1 and 2 years post-transplant.
- Hematologic Function [ Time Frame: Day 100, 6 months ] [ Designated as safety issue: Yes ]Hematologic function will be defined by absolute neutrophil count (ANC) greater than 1500, Hemoglobin greater than 10g/dL without transfusion support, and platelets greater than 100,000 and measured at Day 100 and 6 months. Use of growth factors will be noted.
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||November 2017|
|Estimated Primary Completion Date:||November 2016 (Final data collection date for primary outcome measure)|
One regimen from either reduced-intensity conditioning (RIC) (Fludarabine and Busulfan; or Fludarabine and Melphalan) or myeloablative conditioning (MAC) (Busulfan and Fludarabine; or Cyclophosphamide and Total Body Irradiation) will be administered prior to allogeneic hematopoietic cell transplantation (HCT).
Drug: Fludarabine and Busulfan
RIC Regimen (Flu/Bu): Fludarabine total dose: 120-180 mg/m^2, Busulfan: ≤ 8 mg/kg PO or 6.4 mg/kg IV). Recommended regimen:
Busulfan will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs more than 125 percent of IBW, in which case the drug will be dosed according to the adjusted IBW.
Other Name: Fludara and BusulfexDrug: Fludarabine and Melphalan
RIC Regimen (Flu/Mel): Fludarabine total dose: 120-180 mg/m^2, Melphalan total dose: less than or equal to 150 mg/m^2. Recommended regimen:
Other Name: Fludara and AlkeranDrug: Busulfan and Fludarabine
MAC Regimen (Bu/Flu): Fludarabine total dose: 120-180mg/m^2 Busulfan total dose less than or equal to 16mg/kg PO or 12.8 mg/kg IV. Recommended regimen:
Other Name: Busulfex and FludaraDrug: Cyclophosphamide and Total Body Irradiation
MAC Regimen (Cy/TBI): Cyclophosphamide total dose: 120 mg/kg, Fractionated TBI total dose: 1200-1420 cGy Recommended regimen:
Cyclophosphamide will be dosed according to the recipient's ideal body weight (IBW), unless the patient weighs less than IBW, in which case the drug will be dosed according to the actual body weight.
Other Name: Cytoxan® and radiation
Please refer to this study by its ClinicalTrials.gov identifier: NCT01410344
|United States, Arizona|
|Mayo Clinic - Phoenix|
|Phoenix, Arizona, United States, 85054|
|United States, California|
|City of Hope National Medical Center|
|Duarte, California, United States, 91010|
|University of CA, SF|
|San Francisco, California, United States, 94143-0324|
|United States, Florida|
|H. Lee Moffitt Cancer Center|
|Tampa, Florida, United States, 33624|
|United States, Georgia|
|Blood & Marrow Transplant Program at Northside Hospital|
|Atlanta, Georgia, United States, 30342|
|United States, Maryland|
|Baltimore, Maryland, United States, 21231|
|United States, Minnesota|
|Mayo Clinic - Rochester|
|Rochester, Minnesota, United States, 55905|
|United States, Pennsylvania|
|University of Pennsylvania Cancer Center|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Texas|
|University of Texas/MD Anderson CRC|
|Houston, Texas, United States, 77030|
|Texas Transplant Institute|
|San Antonio, Texas, United States, 78229|
|United States, Wisconsin|
|Medical College of Wisconsin|
|Milwaukee, Wisconsin, United States, 53211|
|Study Director:||Mary Horowitz, MD||Center for International Blood and Marrow Transplant Research|