Donor Stem Cell Transplant using Alpha/Beta+ T-Cell Depletion in Treating Patients with Hematologic Malignancies

Inclusion Criteria

• Patients with any of the following hematologic malignancies who are considered to be eligible for allogeneic transplantation: * Acute lymphoid leukemia (ALL) in first complete remission (CR1) with high risk for relapse including: ** Detectable minimal residual disease by either multicolor flow cytometry or by genomic assay after initial induction therapy ** t(9;22) or detected BCR-ABL1 translocation by genomic methodologies ** BCR-ABL1-Like B-ALL including mutations of IKZF1 or CRLF2 ** Translocations or mutations involving 11q23 (MLL) gene ** Hypodiploid karyotype ** Deletion of 9p ** Loss of 17p or TP53 mutation ** T-lymphocyte lineage antigen expression (T-ALL) ** Prior central nervous system (CNS) or other extramedullary involvement ** White blood cell count (WBC) count >= 100,000 cells/uL at diagnosis * Acute biphenotypic or bilineal leukemia in CR1 * Acute myeloid leukemia (AML) in CR1 with ** Detectable minimal residual disease (MRD) by either multicolor flow cytometry or by genomic assay after initial induction therapy ** In the absence of MRD any intermediate or high risk features according to the European LeukemiaNet 2017 guidelines, including: *** Mutated FLT3-ITD or FLT3-TKD *** Cytogenetic abnormalities not classified as favorable *** Cytogenetic abnormalities associated with myelodysplastic syndrome including abnormalities of chromosome 5, 7, or 17p *** Complex karyotype or monosomal karyotype *** t(9;11)(p21.1;q23.3); MLL-KMT2A or other rearrangements of KMT2A *** t(9;22); BCR-ABL1 *** Inversions or translocations of chromosome 3 *** T(6;9)(p23;q34.1); DEK-NUP214 *** Somatic mutation of RUNX1, ASXL1 or TP53 ** Extramedullary involvement ** WBC count >= 100,000 cells/uL at diagnosis * Relapsed acute leukemia with =< 5% blasts in the bone marrow prior to transplantation (i.e. second complete response [CR2] or greater) * Myelodysplastic syndrome, myeloproliferative neoplasms, or MDS/myeloproliferative neoplasms (MPN) overlap syndrome with =< 10% blasts and at least one of the following: ** Revised International Prognostic Scoring System (IPSS) risk score of intermediate (INT), HIGH, or VERY HIGH at the time of transplant evaluation ** Life-threatening cytopenias ** 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 ** Therapy related disease or disease evolving from other malignant processes * Chronic myelomonocytic leukemia (CMML) with =< 10% blasts prior to transplantation * Chronic myeloid leukemia (CML) meeting one of the following criteria: ** Failed or are intolerant to BCR-ABL tyrosine kinase inhibitors ** CML with BCR-ABL mutation consistent with poor response to tyrosine kinase inhibition (e.g. T351I mutation) ** CML with accelerated or blast phase with < 10% blasts after therapy * Chronic lymphocytic leukemia (CLL) with high risk disease as defined by the European Group for Blood and Marrow Transplantation (EBMT) consensus criteria * Hodgkin lymphoma meeting both of the following criteria: ** Responding to therapy prior to enrollment ** Relapse after autologous bone marrow transplant or are ineligible for autologous bone marrow transplant * Non-Hodgkin lymphoma meeting both of the following criteria: ** Responding to therapy prior to enrollment ** Relapse after prior autologous bone marrow transplant or are ineligible for autologous bone marrow transplant
• Patients must have Karnofsky/Lanksy performance status >= 70%
• Cardiac left ventricular ejection fraction >= 50% at rest
• Serum bilirubin =< 2 mg/dL. Patients with Gilbert’s disease or ongoing hemolytic anemia are acceptable if the direct bilirubin is =< 2 mg/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) unless thought to be disease related
• Estimated or measured creatinine clearance > 50 mL/min/1.73 m^2 body surface area
• Adult patients and pediatric patients capable of performing pulmonary function studies must have hemoglobin adjusted pulmonary diffusion lung capacity (DLCO) >= 50% of predicted
• DONOR: Partially HLA-matched unrelated volunteers (allele level matched at 6-7 of 8 HLA loci: -A, -B, -C, and -DRB1) are eligible
• DONOR: Related, haploidentical donors are eligible
• DONOR: Able to provide informed consent to the donation process
• DONOR: Meet standard criteria for donor collection as defined by the National Marrow Donor Program Guidelines

Exclusion Criteria

• Persons with a HLA matched sibling donor or a 8/8 allele level HLA-matched unrelated donor
• Female patients who are pregnant or breast-feeding
• Persons with an infection that is not responding to antimicrobial therapy
• Persons who are seropositive for human immunodeficiency virus (HIV)
• Persons with active/detectable central nervous system malignancy
• Persons who do not meet the age and organ function criteria specified above
• Presence of psychiatric or neurologic disease, or lack of social support that limits the patient’s ability to comply with the treatment protocol including supportive care, follow-up, and research tests
• Prior allogeneic hematopoietic cell transplantation are ineligible
• Patients with history of other malignancy within 5 years of study therapy are ineligible with the following exceptions: Low grade prostate cancer (Gleason’s =< 6) treated with curative intent, breast ductal carcinoma in situ treated with curative intent, or non-melanomatous skin carcinomas
• Patients with previous checkpoint inhibitor therapy such as PD-1/PDL-1 inhibitors cannot undergo transplantation less than 6 weeks from the last checkpoint inhibitor therapy