Vorinostat, Tacrolimus, and Methotrexate in Preventing GVHD After Stem Cell Transplant in Patients With Hematological Malignancies

Inclusion Criteria

• A prospective patient for allogeneic HSCT for hematologic conditions, both malignant and non-malignant; donor can be unrelated marrow or peripheral blood cells; a patient with history of central nervous system (CNS) involvement is eligible if CNS disease is in remission at time of study consideration
• The donor and recipient must have a human leukocyte antigen (HLA)-8/8 allelic match at the HLA-A, -B, -C, and -DRB1; high-resolution typing is required for all alleles
• Diagnoses to be included:
• Acute myelogenous leukemia at the following stages:
• First remission
• Second or subsequent remission
• Complete remission is defined as the absence of blasts in the peripheral circulation at the time of enrollment and 0% but 50 x 10^9/L despite therapy)
• Rapid doubling of WBC ( 1000 x 10^9/L)
• Cytogenetic abnormalities in addition to Ph+
• Increasing splenomegaly
• Marrow fibrosis
• Myelodysplastic syndromes at any of the following stages:
• Refractory anemia
• Refractory anemia with ringed sideroblasts
• Refractory cytopenia with multilineage dysplasia
• Refractory cytopenia with multilineage dysplasia and ringed sideroblasts
• Refractory anemia with excess blasts-1 (5-10% blasts)
• Refractory anemia with excess blasts-2 (10-20% blasts)
• Myelodysplastic syndrome, unclassified
• Myelodysplastic syndrome (MDS) associated with isolated del (5q)
• Chronic myelomonocytic leukemia
• Primary Myelofibrosis
• Intermediate-2 risk or high risk disease
• Patients should have extinguished standard of care options prior to being considered for this trial
• Chronic lymphocytic leukemia
• Complete remission: the disease is completely absent and no relapse occurred prior to the preparative regimen; requires all of the following:
• Nodular partial remission: complete response with persistent lymphoid nodules in bone marrow
• Partial remission: reduction of more than 50% in the disease burden regardless of the number of lines of therapy received
• Mature B cell malignancies
• Patients should have extinguished standard of care options prior to being considered eligible for this trial
• First complete remission (CR1) confirmed: complete disappearance of all known disease; the term "confirmed" is defined as a laboratory and/or pathological or radiographic determination.
• CR1 unconfirmed (CRU1): complete disappearance of all known disease with the exception of persistent scan abnormalities of unknown significance; the term "unconfirmed" is defined as scan abnormalities of unknown significance that are not biopsied or otherwise evaluated
• Second or subsequent complete remission (CR2+) confirmed: the recipient relapsed, then achieved complete absence of disease without radiographic evidence of disease
• CR2+ unconfirmed: the recipient has achieved a second or subsequent complete response but has persistent radiographic abnormalities of unknown significance.
• Partial remission: reductions of >= 50% in greatest diameter of all sites of known disease and no new sites
• Karnofsky >= 70%
• Life expectancy of greater than 6 months
• Total bilirubin = 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal; GFR should be corrected for body surface area (BSA)
• Diffusing capacity of the lung for carbon monoxide (DLCO) > 50%; DLCO should be corrected for hemoglobin
• Forced expiratory volume in 1 second (FEV1) > 50%
• Forced vital capacity (FVC) > 50%
• Ejection fraction >= 50%
• The effects of vorinostat on the developing human fetus are unknown; for this reason and because histone deacetylase inhibitor agents as well as other therapeutic agents used in this trial (e.g., tacrolimus and methotrexate) are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her