Allogeneic Hematopoietic Stem Cell Transplantation of α/β T-Lymphocyte Depleted Graft Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia
Overview
- Phase
- Phase 1
- Intervention
- Antithymocyte globulin (Rabbit)
- Conditions
- Myeloid Diseases
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 17
- Locations
- 2
- Primary Endpoint
- Rate of donor Neutrophil Engraftment
- Status
- Active, not recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
The main purpose of this study is to learn if a new combination of chemotherapy, in combination with low-dose radiation, will be safe for the patient, and at the same time provide the best opportunity to cure the bone marrow cancer. The combination of chemotherapy and radiation described in the study is considered 'low intensity.' Although the chemotherapy agents used in this study and for transplant are FDA approved, the chemotherapy treatment and conditioning regimens or combinations listed in this consent are not yet FDA approved.
The CliniMACS device is FDA approved for one type of T cell depletion (positive selection of the stem cells) but not approved yet for other type of T cell depletion, which is being studied on this protocol. This pilot study, along with other studies will serve as the basis for FDA approval, if outcomes are favorable.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients with one of the high risk myeloid diseases as outlined below. Patients must have ≤ 5% blasts on the last BM evaluation prior to starting the conditioning regimen. Diseases included on this protocol include:
- •Acute Myeloid Leukemia (AML) in CR1 with intermediate or high risk features as defined below:
- •°Cytogenetic abnormalities which are not considered "good risk" cytogenetic features (i.e t(8:21), t(15:17), inv 16 without c-kit mutations.
- •Therapy related AML with history of antineoplastic therapy (radiation and/or chemotherapy) And/or
- •Normal karyotype with mutations of FLT3, RUNX1, TP53 mutation, ASXL1 or any others that are considered to be high risk
- •AML in ≥ 2nd remission
- •Myelodysplastic syndrome, myeloproliferative neoplasms, or MDS/MPN overlap syndrome with:
- •°International prognostic scoring system risk score INT-2 or high risk at the time of transplant evaluation.
- •Any risk category if life-threatening cytopenia exists And/or
- •Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.
Exclusion Criteria
- •Prior allogenic hematopoietic stem cell transplantation
- •Prior radiation therapy with 400cGY or more of TBI
- •BM with increased fibrosis (Reticulin stain \> 1/3)
- •Active and uncontrolled infection at time of transplantation
- •HIV infection
- •Seropositivity for HTLV-1
- •Inadequate performance status/ organ function
- •Pregnancy or breast feeding
- •Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and research tests.
- •Donor Inclusion and Exclusion Criteria:
Arms & Interventions
Patients with Myeloid Malignancies & Aplastic Anemia
Transplant conditioning will consist of: ATG (2 mg/kg/day IV on days-8 through-6), fludarabine (30 mg/m\^2/d on days -5 through -2), TBI 400 cGy in 2 divided doses (days -2 and -1) and high dose cyclophosphamide given post stem cell infusion (50 mg/kg on days +3 and +4). One dose of Rituxan (200 mg/m\^2) will be given to reduce the risk of EBV viremia. The donor stem cell product will be derived from the peripheral blood with a target cell infusion of ≥8X10\^6 CD34 cells per recipient kg. Patients will receive post-transplant G-CSF starting on day +7. Patients will undergo donor/recipient bone marrow and peripheral chimerism studies at 30 and 100, and 6, 12, 18 and 24 months post allo HCT and thereafter, at the discretion of the treating clinician. Immune function and disease restaging will be performed at day 100 and 6, 12, 18, and 24 months and as otherwise clinically indicated by the treating physician.
Intervention: Antithymocyte globulin (Rabbit)
Patients with Myeloid Malignancies & Aplastic Anemia
Transplant conditioning will consist of: ATG (2 mg/kg/day IV on days-8 through-6), fludarabine (30 mg/m\^2/d on days -5 through -2), TBI 400 cGy in 2 divided doses (days -2 and -1) and high dose cyclophosphamide given post stem cell infusion (50 mg/kg on days +3 and +4). One dose of Rituxan (200 mg/m\^2) will be given to reduce the risk of EBV viremia. The donor stem cell product will be derived from the peripheral blood with a target cell infusion of ≥8X10\^6 CD34 cells per recipient kg. Patients will receive post-transplant G-CSF starting on day +7. Patients will undergo donor/recipient bone marrow and peripheral chimerism studies at 30 and 100, and 6, 12, 18 and 24 months post allo HCT and thereafter, at the discretion of the treating clinician. Immune function and disease restaging will be performed at day 100 and 6, 12, 18, and 24 months and as otherwise clinically indicated by the treating physician.
Intervention: fludarabine
Patients with Myeloid Malignancies & Aplastic Anemia
Transplant conditioning will consist of: ATG (2 mg/kg/day IV on days-8 through-6), fludarabine (30 mg/m\^2/d on days -5 through -2), TBI 400 cGy in 2 divided doses (days -2 and -1) and high dose cyclophosphamide given post stem cell infusion (50 mg/kg on days +3 and +4). One dose of Rituxan (200 mg/m\^2) will be given to reduce the risk of EBV viremia. The donor stem cell product will be derived from the peripheral blood with a target cell infusion of ≥8X10\^6 CD34 cells per recipient kg. Patients will receive post-transplant G-CSF starting on day +7. Patients will undergo donor/recipient bone marrow and peripheral chimerism studies at 30 and 100, and 6, 12, 18 and 24 months post allo HCT and thereafter, at the discretion of the treating clinician. Immune function and disease restaging will be performed at day 100 and 6, 12, 18, and 24 months and as otherwise clinically indicated by the treating physician.
Intervention: total body irradiation
Patients with Myeloid Malignancies & Aplastic Anemia
Transplant conditioning will consist of: ATG (2 mg/kg/day IV on days-8 through-6), fludarabine (30 mg/m\^2/d on days -5 through -2), TBI 400 cGy in 2 divided doses (days -2 and -1) and high dose cyclophosphamide given post stem cell infusion (50 mg/kg on days +3 and +4). One dose of Rituxan (200 mg/m\^2) will be given to reduce the risk of EBV viremia. The donor stem cell product will be derived from the peripheral blood with a target cell infusion of ≥8X10\^6 CD34 cells per recipient kg. Patients will receive post-transplant G-CSF starting on day +7. Patients will undergo donor/recipient bone marrow and peripheral chimerism studies at 30 and 100, and 6, 12, 18 and 24 months post allo HCT and thereafter, at the discretion of the treating clinician. Immune function and disease restaging will be performed at day 100 and 6, 12, 18, and 24 months and as otherwise clinically indicated by the treating physician.
Intervention: cyclophosphamide
Patients with Myeloid Malignancies & Aplastic Anemia
Transplant conditioning will consist of: ATG (2 mg/kg/day IV on days-8 through-6), fludarabine (30 mg/m\^2/d on days -5 through -2), TBI 400 cGy in 2 divided doses (days -2 and -1) and high dose cyclophosphamide given post stem cell infusion (50 mg/kg on days +3 and +4). One dose of Rituxan (200 mg/m\^2) will be given to reduce the risk of EBV viremia. The donor stem cell product will be derived from the peripheral blood with a target cell infusion of ≥8X10\^6 CD34 cells per recipient kg. Patients will receive post-transplant G-CSF starting on day +7. Patients will undergo donor/recipient bone marrow and peripheral chimerism studies at 30 and 100, and 6, 12, 18 and 24 months post allo HCT and thereafter, at the discretion of the treating clinician. Immune function and disease restaging will be performed at day 100 and 6, 12, 18, and 24 months and as otherwise clinically indicated by the treating physician.
Intervention: Rituxan
Patients with Myeloid Malignancies & Aplastic Anemia
Transplant conditioning will consist of: ATG (2 mg/kg/day IV on days-8 through-6), fludarabine (30 mg/m\^2/d on days -5 through -2), TBI 400 cGy in 2 divided doses (days -2 and -1) and high dose cyclophosphamide given post stem cell infusion (50 mg/kg on days +3 and +4). One dose of Rituxan (200 mg/m\^2) will be given to reduce the risk of EBV viremia. The donor stem cell product will be derived from the peripheral blood with a target cell infusion of ≥8X10\^6 CD34 cells per recipient kg. Patients will receive post-transplant G-CSF starting on day +7. Patients will undergo donor/recipient bone marrow and peripheral chimerism studies at 30 and 100, and 6, 12, 18 and 24 months post allo HCT and thereafter, at the discretion of the treating clinician. Immune function and disease restaging will be performed at day 100 and 6, 12, 18, and 24 months and as otherwise clinically indicated by the treating physician.
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation
Outcomes
Primary Outcomes
Rate of donor Neutrophil Engraftment
Time Frame: 30 days post-transplant
Neutrophil engraftment (recovery of ANC) defined by an ANC ≥ 500/mm\^3 for 3 consecutive days