azacitidine in haploidentical donor hematopoietic cell transplantation

Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndrome; Acute Lymphocytic Leukemia

Summary: allogeneic hematopoietic cell transplantation (allo-hct) is a potentially curative therapy for patients with hematologic malignancies including acute myeloid leukemia (aml), myelodysplastic syndrome (mds), and acute lymphoblastic leukemia (all); however, human leukocyte antigen (hla)-matched donor availability continues to be a major hurdle. historically, hla haploidentical donor hematopoietic cell transplantation (haplo-hct) was associated with high incidences of graft rejection and excessive non-relapse mortality (nrm), but recent advances utilizing post-transplant cyclophosphamide (pt-cy) have revolutionized haplo-hct and the outcomes are now comparable to allo-hct using more traditional hla matched related and unrelated donors. however, graft-versus-host disease (gvhd) continues to be a problem and is associated with significant morbidity and mortality in allo-hct patients including those who receive haplo-hct on pt-cy platform. the aim of this early phase study is to investigate the safety and overall efficacy of azacitidine in reducing the incidence and severity of gvhd when added to pt-cy based haplo-hct platform for patients with aml, all, or advanced mds.


Eligibility criteria:
inclusion criteria: * diagnosis of acute leukemia (aml/all) or advanced mds (int-2 or high risk) in complete remission (cr/crc/cri) documented by bone marrow biopsy done within 30 days prior to the initiation of conditioning regimen. * available hla-haploidentical donor that meets the following criteria: * immediate family member (sibling, offspring, or parent) * at least 18 years of age * hla-haploidentical donor/recipient match by class i serologic typing at the a\&b locus. * in the treating physician's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting hsc * no active hepatitis (b, c), htlv, and hiv infections * not pregnant * karnofsky performance status ≥ 70 % * adequate organ function as defined below: * total bilirubin ≤ 2.5 mg/dl (unless the patient has a history of gilbert's syndrome) * ast(sgot) and alt(sgpt) ≤ 3.0 x iuln * creatinine ≤ 2.0 x iuln or estimated creatinine clearance ≥ 30 ml/min/1.73 m\^2 by cockcroft-gault formula * oxygen saturation ≥ 90% on room air * lvef ≥ 40% * fev1 and fvc ≥ 50% predicted, corrected dlco ≥ 40% predicted * at least 18 years of age at the time of study registration * able to understand and willing to sign an irb approved written informed consent document (or that of legally authorized representative, if applicable) exclusion criteria: * recipients with donor sensitive antibodies (dsa), defined by 2000 or higher mfi against one or more class i or ii antigens * known hiv or active hepatitis b or c infection * underwent a previous related or unrelated allogeneic transplant * known hypersensitivity to one or more of the study agents * currently receiving or has received any investigational drugs within the 14 days prior to the first dose of the conditioning regimen. * pregnant and/or breastfeeding * uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or unstable cardiac arrhythmias. * presence of a readily available 6/6 matched sibling donor who is a candidate for donation