Calcineurin Inhibitor-Free Interventions BMT CTN 1301 for Prevention of Graft-versus-Host Disease (BMT CTN 1301)

Inclusion Criteria

• Males and females aged ≥ 1.0 year and 12 years) greater than 50.0 mL/minute (using the Cockcroft-Gault formula and actual body weight); for pediatric patients (> 1 year to 12 years), Glomerular Filtration Rate (GFR) estimated by the updated Schwartz formula ≥ 90.0 mL/min/1.73 m^2. If the estimated creatinine clearance is 70.0 mL/min/1.73 m^2.
• Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 50% (adjusted for hemoglobin), and forced expiratory volume in one second (FEV1) or forced vital capacity (FVC) ≥ 50%; for children who are unable to perform for Pulmonary Function Tests (PFTs) due to age or developmental ability, there must be no evidence of dyspnea and no need for supplemental oxygen, as evidenced by O2 saturation ≥ 92% on room air.
• Liver function: total bilirubin < 2x the upper limit of normal (unless elevated bilirubin is attributed to Gilbert's Syndrome) and alanine aminotransferase (ALT) / aspartate aminotransferase (AST) < 2.5x the upper limit of normal.
• Signed informed consent.

Exclusion Criteria

• Prior autologous or allogeneic hematopoietic stem cell transplant
• Karnofsky or Lansky Performance Score < 70%
• Active central nervous system (CNS) involvement by malignant cells
• Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment
• Presence of fluid collection (ascites, pleural or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated
• Patients seropositive for HIV-1 or -2
• Patients seropositive for Human T-Lymphotrophic Virus (HTLV)-I or -II
• Patients with active Hepatitis B or C viral replication by polymerase chain reaction (PCR)
• Documented allergy to iron dextran or murine proteins
• Women who are pregnant (positive serum or urine βHCG) or breastfeeding
• Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use 2 effective forms of birth control or abstinence for one year after transplantation
• History of uncontrolled autoimmune disease or on active treatment
• Patients with prior malignancies, except resected non-melanoma 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 will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.
• Patient unable to comply with the treatment protocol including appropriate supportive care, follow-up and research tests
• Planned post-transplant maintenance therapy except for FLT3 inhibitors or TKIs must be declared prior to randomization.
• If it is known prior to enrollment that the hematopoietic stem cell product will need to be cryopreserved, the patient should not be enrolled.
• German centers only: Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or participation in any other interventional clinical study.