Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft

Eligibility Criteria

• * Acute myeloid, lymphoid, or mixed phenotype leukemia in complete remission (CR) or CR with incomplete hematologic recovery (CRi) or beyond first complete remission (CR1) without the presence of minimal residual disease
• * Acute myeloid, leukemia, or mixed phenotype leukemia that is either:
• * Not in morphologic CR with bone marrow infiltration by leukemic blasts of ≤10%, or
• * In morphologic CR with evidence of minimal residual disease positivity by either multiparametric flow cytometric analysis or by a nucleic acid-based technique
• * Primary refractory acute myeloid, lymphoid, or mixed phenotype leukemia
• * Chronic myelogenous leukemia (accelerated, blast or second chronic phase)
• * Myelodysplastic syndromes
• * Myeloproliferative syndromes b. Match to the patient as follows: a. For Arm A1 (CLOSED):
• * Availability of a 8/8 or 7/8 HLA-matched donor (related or unrelated) defined by Class I (HLA-A, -B, -C) serologic typing (or higher resolution) and Class II (HLA-DRB1) molecular typing.
• * If the donor is a 7/8 HLA-match, the mismatch must be a permissive allelic mismatch as assessed by an independent HLA and transplantation expert. b. For Arm A1 and Arm A3:
• * Availability of a 8/8 HLA-matched donor (related or unrelated) defined by Class I (HLA-A, -B, -C) serologic typing (or higher resolution) and Class II (HLA-DRB1) molecular typing.
• * Availability of a haploidentical donor who is a ≥ 4/8 but \<7/8 match at HLA-A, -B, -C, and -DRB1 (typed using DNA-based high-resolution methods), with at most one mismatch per locus d. For Arm C1 (CLOSED) and C2:
• * Availability of a 8/8 HLA matched donor (related or unrelated) defined by Class I (HLA-A, B, C) serologic typing (or higher resolution) and Class II (HLA DRB1) molecular typing.
• 1. Age ≥ 18 and ≤ 75 years of age
• 2. Karnofsky performance status of ≥ 70% defined by institutional standards
• 3. Seronegative for HIV-1 RNA PCR; HIV 1 and HIV 2 ab (antibody); HTLV-1 and HTLV-2 ab; PCR+ or sAg (surface antigen) hepatitis B ; or PCR or sAg negative for hepatitis C; negative for the Treponema palladum antibody Syphillis screen; and negative for HIV-1 and hepatitis C by nucleic acid testing (NAT) within 30 days of apheresis collection.
• 4. In the case that T palladum antibody tests are positive, donors must:
• 1. Arm A1(CLOSED):
• 2. Arm A2 and Arm A3:
• 3. Arm B (CLOSED):
• * Must be a haploidentical donor who is ≥ 4/8 but \< 7/8 match at HLA-A, -B, -C, and -DRB1, with at most one mismatch per locus.
• 4. Arm C1 (CLOSED) and Arm C2:
• * Must be a related or unrelated 7/8 HLA matched to recipient at HLA A, B, C, DRB1 or -DQB1
• * The donor is a first-degree or second-degree blood relative of the recipient, or
• * Documented urgent medical need (DUMN), meaning no comparable human cell product is available and the recipient is likely to suffer death or serious morbidity without the human cell product, as attested by the Investigator or sub-investigator
• 1. Seropositive for any of the following:
• 2. Patients deemed candidates for fully myeloablative preparative conditioning regimens
• * A positive crossmatch of any titer; or
• * The presence of anti-donor HLA antibody to any HLA locus n. Any uncontrolled autoimmune disease requiring active immunosuppressive treatment o. Concurrent malignancies or active disease within 1 year, except nonmelanomatous skin cancers that have been curatively resected
• 1. Evidence of active infection
• 2. Seropositive for HIV-1 or-2, HTLV-1 or -2
• 3. Medical, physical, or psychological reason that would place the donor at increased risk for complications from growth factor or leukapheresis
• 4. Lactating female