Co-Principal Investigators: Joseph Alvarnas, MD and Richard Ambinder, MD
Study Design: The study is designed as a Phase II multicenter trial.
Primary Objective: 100 day non-relapse mortality (NRM).
Secondary Objectives: Patients wil be assessed for the following endpoints:
- Disease status at Day 100 post-HCT
- Time to hematopoietic recovery
- Chimerism at 30, 100 and 180 days
- Hematologic function at 100 and 180 days
- Infections
- Six-month overall survival
- Acute graft-vs.-host disease
- Chronic graft-vs.-host disease
- Immunologic reconstitution at 8 weeks, 180 and 365 days
- Impact of HCT on the HIV reservoir at Day 100, 6 months, 1 year and 2 years post HCT
Accual Objective: The trial will accrue 15 patients.
Accrual Period: The estimated accrual period is 2 years.
Eligibility Criteria: Patients > 15 years old, HIV-infected and diagnosed with acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) in first or second complete remission (CR); Int-2 or high-risk myelodysplastic syndrome (MDS) with < 10% marrow blasts and no circulating myeloblasts after their most recent therapy; or Hodgkin or non-Hodgkin lymphoma beyond first CR with at least a partial response to last treatment. Patients must either have an 8/8 match (HLA-A, -B, -C, and -DR) related donor or at least 7/8 high resolution matched unrelated donor. A secondary matching criterion is the presence of homozygosity for the CCR5 delta32 mutation. Allogeneic transplantation using cord blood and prior allogeneic HCT are not allowed for this study.
Patients must have adequate organ function defined as 1) left ventricular ejection fraction at rest > 40%; 2) DLCO, FEV1, FVC > 45% predicted; 3) total bilirubin < 2.0 mg/dL, and ALT and AST < 5 x upper limit of normal (ULN); 4) serum creatinine > 40 mL/min. Karnofsky/Lansky performance status > 70%.
Treatment Description: Patients with HIV infection and hematological malignancies or myelodysplastic syndromes (MDS) will be treated with either reduced-intensity or fully ablative allogeneic hematopoietic cell transplantation (HCT). Where feasible, an attempt will be made to identify hematopoietic cell donors who are homozygotes for the CCR5 delta32 mutation. Patients will receive standard immunosuppressive therapy post-transplant that will be tapered as per the institutional standard of care. Graft-versus-host disease will be treated per the institutional standard of care.
Study Duration: Patients will be followed for two years following allogeneic HCT.