Anti-Thymocyte Globulin added to Tacrolimus and Methotrexate for Reducing Graft Versus Host Disease after Hematopoietic Stem Cell Transplant for Hematologic Cancers

Inclusion Criteria

• Adult male or female, age 18-75 years
• Patients must have a related or unrelated peripheral blood stem cell donor. Sibling donor must be a 6/6 match for human leukocyte antigen (HLA)-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using deoxyribonucleic acid (DNA)-based typing, and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation. Unrelated donor must be 8/8 match at HLA-A, -B, -C and –DRB1 at high resolution using DNA-based typing. Unrelated donor must be willing to donate peripheral blood stem cells and be medically eligible to donate stem cells according to National Marrow Donor Program (NMDP) criteria
• A candidate for reduced intensity preparative regimen, based on age >= 60, or hematopoietic cell transplantation-comorbidity index (HCT-CI) of >= 4, or considered by the treating physician to have high risk for toxicity with myeloablative preparative regimen
• Cardiac function: Ejection fraction >= 40%
• Calculated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault formula and actual body weight)
• Pulmonary function: Diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% (adjusted for hemoglobin) and forced expiratory volume in 1 second (FEV1) >= 50%
• Total bilirubin < 1.5 x the upper limit of normal * Patients who have been diagnosed with Gilbert’s disease are allowed to exceed the defined bilirubin value up to < 3mg/dl
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5 x the upper normal limit
• Female subjects (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two effective methods of contraception or agree to complete abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant
• Male subjects (even if surgically sterilized), of partners of women of childbearing potential must agree to practice effective barrier contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 12 months post-transplant
• Karnofsky performance status (KPS) >= 70
• Patients must have a diagnosis of one of the following: * Acute myeloid leukemia (AML) in complete remission (CR) 1 with intermediate or high risk for relapse as defined by European LeukemiaNet (ELN) 2022 criteria, or deemed to be at high risk for relapse by treating physician, based on age >= 60, therapy related, or extra medullary presentation * AML in > CR1 * Myelodysplastic syndrome (MDS) with Molecular International Prognostic Scoring System (IPSS-M) >= intermediate-low * Chronic myeloproliferative disorder (essential thrombocythemia [ET], polycythemia vera [PV], myelofibrosis) with bone marrow blasts > 5% and/or other evidence of progression to acute leukemia or intermediate (Int) or high-risk disease by Mutation-Enhanced International Prognostic Score System (MIPPS) version (v)2 score * Chronic myelomonocytic leukemia (CMML) especially those with high-risk features based in: The CMML-specific prognostic scoring system with molecular features (CPSS-Mol) - high risk and intermediate-2 risk, Mayo molecular model - high risk and intermediate-2 risk, Groupe Francophone des Myelodysplasies (GFM) - high risk and selected patients with intermediate risk * Acute lymphoblastic leukemia (ALL) in CR1 with high risk for relapse ** B-cell ALL: High white blood cell count at diagnosis (ie, > 30,000/ul), clonalcytogenetic abnormalities - t(4;11), t(1;19), t(9;22), or BCR-ABL gene positivity, BCR-ABL1-like (Ph-like) gene signature, progenitor-B cell immunophenotype (eg, blasts expressing membrane CD19, CD79a, and cytoplasmic CD22, but not CD10), length of time from start of induction therapy to attainment of CR greater than four weeks, older age - > 60 years old is high risk, 30 to 59 years old is intermediate risk, and minimal residual disease (MRD) post-remission bone marrow MRD+ ** T-cell ALL: Failure to achieve CR after one induction, MRD > 1 x 10^-4 after 2 courses of induction, presenting white blood cell (WBC) > 100 x 10^9/L, complex cytogenetics >= 5, early T-cell precursor ALL, poor risk genetics including lack of NOTCH1 with/FBXW7 or presence of N-RAS & K-RAS, EZH2 and age > 40 years * ALL in > CR1
• The subject is willing and able to sign informed consent and abide by the protocol requirements

Exclusion Criteria

• Autologous hematopoietic stem cell transplant < 3 months prior to enrollment
• Patients with florid residual AML with > 5% blast in the marrow or circulating blast in the peripheral blood are not eligible for this study
• Previous allogeneic stem cell transplant
• Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiogram (EKG) suggestive of acute ischemia or active conduction system abnormalities
• Known hypersensitivity to the study agent (ATG)
• Received any investigational drugs within the 14 days prior to the first day of transplant conditioning
• Pregnant and/or breastfeeding
• Evidence of HIV infection or known HIV positive serology
• Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings)
• Non-hematologic malignancy within prior three (3) years, with the exception of squamous cell or basal cell skin carcinoma. Patients with prior malignancies except resected localized non-melanoma skin cancer or treated cervical carcinoma in situ. Cancer treated with curative intent >= 5 years previously will be allowed. Cancer treated with curative intent < 5 years previously must be reviewed and approved by the principal investigator (PI)
• Participation in another clinical study with an investigational product during the last 28 days
• Patients with documented cirrhosis