Clinical trial NCT02750254: Azacitidine in Haploidentical Donor Hematopoietic Cell Transplantation
Official title: A Phase I/II Study of Azacitidine in Haploidentical Donor Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndrome
Acute Lymphocytic Leukemia
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2016-04-25
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Safety of azacitidine (Phase I only) as measured by frequency and grade of adverse events
timeFrame: Up to Day 35
measure: Maximum tolerated dose of azacitidine (Phase I only)
timeFrame: Estimated to be 3-4 months (completion of all Phase I patients through Day 35)
measure: Grade II-IV acute GvHD rate of azacitidine (Phase II only)
timeFrame: Up to Day 100
Secondary outcomes:
measure: Event-free survival (EFS)
timeFrame: Up to 48 months
measure: Overall survival (OS)
timeFrame: Up to 48 months
measure: Disease-free survival (DFS)
timeFrame: Up to 48 months
measure: Non-relapse mortality (NRM)
timeFrame: Up to Day 100
measure: Time to neutrophil engraftment
timeFrame: Up to 12 months
measure: Time to platelet engraftment
timeFrame: Up to 12 months
measure: Rate of acute GvHD
timeFrame: Up to Day 100
measure: Rate of chronic GvHD
timeFrame: Day 100 through Day 365
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Mark Schroeder, M.D.
role: PRINCIPAL_INVESTIGATOR
References: