Allogeneic Hematopoietic Cell Transplant for Hematological Cancers and Myelodysplastic Syndromes in HIV-Infected Individuals (BMT CTN #0903)
Overview
- Phase
- Phase 2
- Intervention
- Fludarabine and Busulfan
- Conditions
- Leukemia
- Sponsor
- Medical College of Wisconsin
- Enrollment
- 20
- Locations
- 11
- Primary Endpoint
- Percentage of Participants With Non-Relapse Mortality
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The rationale for this trial is to demonstrate the feasibility and safety of allogeneic HCT for patients with chemotherapy-sensitive hematological malignancies and coincident HIV-infection. In particular, the trial will focus on the 100-day non-relapse mortality as an indicator of the safety of transplant in this patient population. Correlative assays will focus upon the incidence of infectious complications in this patient population, the evolution of HIV infection and immunological reconstitution. Where feasible (and when this can be accomplished without compromise of either the donor quality or the timeliness of transplantation), an attempt will be made to identify donors who are homozygotes for the delta32 mutation for CCR5.
Detailed Description
The study is designed to evaluate the feasibility and safety of reduced-intensity and fully-ablative allogeneic hematopoietic cell transplantation (HCT) for patients with hematological malignancies or myelodysplastic syndromes (MDS) who have HIV infection. The goal of the study is to assess the 100 day Non-relapse Mortality as well as immunological reconstitution in this patient population. Where feasible, an attempt will be made to identify human leukocyte antigen (HLA)-compatible hematopoietic stem cell donors who are homozygotes for the delta32 mutation of the chemokine receptor 5 (CCR5delta32). Patients will undergo a treatment plan review prior to registration on the trial. All patients will undergo allogeneic HCT from a matched sibling or unrelated donor.
Investigators
Eligibility Criteria
Inclusion Criteria
- •HIV-1 infection, as documented by a rapid HIV test or any FDA-Approved HIV-1 Enzyme or Chemiluminescence Immunoassay (E/CIA) test kit and confirmed by Western Blot at any time prior to study entry. HIV antigen, plasma HIV-1 RNA, or a secondary antibody test by a method other than rapid HIV and E/CIA is acceptable as an alternative test. Alternatively, if a rapid HIV test or any FDA-Approved HIV-1 Enzyme or Chemiluminescence Immunoassay (E/CIA) test is not available, two HIV-1 RNA values ≥ 2000 copies/mL at least 24 hours apart performed by any laboratory that has CLIA certification, or its equivalent, may be used to document infection.
- •Patients must be willing to comply with effective Antiretroviral Therapy.
- •Patients must be ≥ 15 years of age.
- •Hematological malignancy associated with a poor prognosis with medical therapy alone. Diagnoses to be included:
- •Patients with the diagnosis of Acute Myeloid or Lymphocytic Leukemia (AML or ALL) in first or second complete remission.
- •Patients with advanced myelodysplastic syndromes (MDS), including those with International Prognostic Scoring System (IPSS) Int-2 and high-risk disease with less than 10% marrow blasts and no circulating myeloblasts after most recent therapy. Patients with acute leukemia that develops from a pre-existing MDS must meet the inclusion criteria for patients with AML detailed above.
- •Hodgkin Lymphoma beyond first remission achieving at least a partial response to most recent therapy with no evidence of progression prior to transplant.
- •Non-Hodgkin Lymphoma beyond first remission achieving at least a partial response to most recent therapy with no evidence of progression prior to transplant.
- •Donor/Recipient HLA Matching:
- •Related donor: must be an 8/8 match at HLA-A, -B, -C, (serologic typing or higher resolution) and -DRB1 (at high resolution using DNA based typing). A 7/8 related donor match is permitted only if an 8/8 unrelated donor cannot be identified.
Exclusion Criteria
- •Karnofsky/Lansky performance score \< 70%.
- •Active central nervous system (CNS) malignancy; however, patients with a history of positive Cerebrospinal fluid (CSF) cytology that has become negative with intrathecal chemotherapy are eligible.
- •Uncontrolled bacterial, viral or fungal infection (currently taking medication and with progression or no clinical improvement).
- •Active Cytomegalovirus (CMV) retinitis or other CMV-related organ dysfunction.
- •AIDS related syndromes or symptoms that pose a perceived excessive risk for transplantation-related morbidity as determined by the principal investigator.
- •Untreatable HIV infection due to multidrug antiretroviral resistance. Patients with a detectable viral load \> 750 copies/ml should be evaluated with an HIV drug resistance test (HIV-1 genotype). The results should be included as part of the Antiretroviral Review (described in Appendix D). This Review Committee will make the final determination as to whether HIV viremia could potentially be suppressed with alternate antiretroviral therapy. .
- •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 allogeneic HCT.
- •Patients with psychosocial conditions that would prevent study compliance and follow-up, as determined by the principal investigator.
Arms & Interventions
Allogeneic Transplant
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).
Intervention: Fludarabine and Busulfan
Allogeneic Transplant
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).
Intervention: Fludarabine and Melphalan
Allogeneic Transplant
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).
Intervention: Busulfan and Fludarabine
Allogeneic Transplant
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).
Intervention: Cyclophosphamide and Total Body Irradiation
Outcomes
Primary Outcomes
Percentage of Participants With Non-Relapse Mortality
Time Frame: Day 100, 1 Year, and 2 Years Post-transplant
The events for non-relapse mortality are death due to any cause other than relapse of the underlying malignancy.
Secondary Outcomes
- Primary Cause of Death(Up to 2 Years Post-transplant)
- Percentage of Participants With Overall Survival(Six months, 1 Year, and 2 Years Post-transplant)
- Percentage of Participants With Acute Graft-Versus-Host Disease (GVHD)(Day 100 Post-transplant)
- Percentage of Participants With Relapse/Progression(1 Year Post-transplant)
- Chimerism(Week 4, Day 100, and 6 months Post-transplant)
- Percentage of Participants With Chronic Graft-Versus-Host Disease (GVHD)(1 Year Post-transplant)
- Infection Severity(1 Year Post-transplant)
- Disease Status(Day 100 Post-transplant)
- Percentage of Participants Recovering Hematologic Function(Days 28 and 100 Post-transplant)