Abatacept Extended Dosing Compared to Abatacept Short-Term Dosing for the Prevention of Graft versus Host Disease, ABA3 Study

Inclusion Criteria

• Must be at least 2 years old and weigh 10 kg. Enrollment of patients age 2-<6 will be suspended after 5 enrolled and treated patients and will only resume after Data and Safety Monitoring Committee (DSMC) review and approval.
• Must have a willing unrelated 8/8 or 7/8 matched adult donor (bone marrow or peripheral blood). Donors may have a single mismatch (i.e. be a 7/8) and this mismatch may be at the allele or antigen level; however, donors with allele level disparity should be given preference over those with antigen level disparity. Patients for whom a donor is available with disparity only in the host versus graft direction (because of recipient homozygosity), will not be eligible, since this mismatching does not increase the risk for GVHD. Centers may perform extended typing (e.g. DQB1 and DPB1) according to institutional practices and use these results in selecting donors; however, it is recommended that this extending typing be used only to select between donors who are equally well matched with the recipient at the A, B, C and DRB1.
• All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
• Must have a hematologic malignancy treatable by HCT (except for those stipulated below under study exclusion criteria), which is in remission by standard testing (no patients in relapse will be included).
• Karnofsky performance score or Lansky Play-Performance Scale score >= 80.

Exclusion Criteria

• Patients with the following hematologic malignancies will be excluded: chronic lymphocytic leukemia, myeloma and primary myelofibrosis.
• Active relapse (> 5% blasts based on morphology and confirmed by multidimensional flow cytometry) of their primary malignancy.
• For patients with acute lymphocytic leukemia (ALL) with pre-transplant minimal residual disease (MRD) testing performed as standard practice at the treating institution, patients with MRD > 0.01% will be ineligible. * Note: For patients with acute myeloid leukemia (AML) with pre-transplant MRD testing by flow as standard of practice at the treating institution, patients with any MRD status are eligible and should be enrolled at the discretion of provider. If a patient is MRD negative by flow but detected positive by PCR, the patient will be discussed with the study team on a case-by-case basis
• For patients with MDS, those with > 5% blasts (based on morphology and confirmed by multidimensional flow cytometry) will be excluded.
• For patients with lymphoma, those with less than a partial metabolic response on positron emission tomography (PET)/computed tomography (CT) will be excluded.
• Prior allogeneic HCT.
• Uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment.
• Human immunodeficiency virus (HIV) infection.
• Serious psychiatric disease including schizophrenia, bipolar disorder and severe depression if uncontrolled and, in the opinion of the treating physician and/or protocol Chair, are likely to interfere with adherence to the protocol activities. If a patient with any of these diseases is well-controlled, they may be enrolled.
• Prisoners or others who are compulsorily detained.
• Any patient with a known or suspected germline predisposition to cancer should be discussed with the study team prior to screening for eligibility. * Patients with a known germline or constitutional predisposition to transplant morbidities, including, but not limited to Fanconi anemia, dyskeratosis congenita, Shwachman Diamond Syndrome and Down Syndrome will be excluded. * Patients with known germline or constitutional predisposition to non-hematologic cancers including, but not limited to Li-Fraumeni syndrome, BRCA1 and BRCA2 mutations will be excluded. * Patients with other predisposition abnormalities will be reviewed on a case-by-case basis.
• Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, and are disease free for < 2 years.
• Incompletely treated active tuberculosis Infection.
• Pregnancy (positive serum beta-human chorionic gonadotropin [b-HCG]) or breastfeeding.
• Estimated glomerular filtration rate (GFR) of < 50 mL/min/1.73 m^2.
• Cardiac ejection fraction < 50 (using M-Mode if assessment is done by echocardiography [ECHO]).
• Total (T) bilirubin > 2 x upper limit of normal or alanine aminotransferase (ALT) > 4 x upper limit of normal or unresolved veno-occlusive disease.
• Pulmonary disease with forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) or carbon monoxide diffusing capability test (DLCO) parameters < 45% predicted (corrected for hemoglobin) or requiring supplemental oxygen. Children who are developmentally unable to perform pulmonary function testing will be assessed solely on their need for supplemental oxygen.
• For patients receiving a 7/8-HLA mismatched transplant, presence of donor specific antibodies to a mismatched donor human leukocyte antigen (HLA) class I antigen (including A, B and C) and/or HLA class II antigen (including DR, DQ and DP).
• EXCLUSION CRITERIA POST-ENROLLMENT RANDOMIZATION: Patients who have developed severe AGVHD, severe CGVHD or relapse will not be randomized, but will remain on-protocol and on-study.
• EXCLUSION CRITERIA POST-ENROLLMENT RANDOMIZATION: Other criteria that will result in a patient not being randomized prior to 5th dose of abatacept/placebo (but who will remain on-protocol and on-study): * Severe allergic reaction during the first 4 doses of abatacept. * If any clinical events occur that preclude further dosing of abatacept, those patients will be deemed ineligible for randomization.