Azacitidine in Haploidentical Donor Hematopoietic Cell Transplantation

NCT ID: NCT02750254

Last Updated: 2020-10-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-27
• Study Completion Date: 2020-10-14

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndrome; Acute Lymphocytic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1: Azacitidine

• Treating physician must choose from one of these conditioning regimens (will be given per standard of care)

• fludarabine and fractionated total body irradiation (Flu/FrTBI)
• fludarabine and busulfan (Flu/Bu4)
• fludarabine, cyclophosphamide, and single dose total body irradiation (Flu/Cy/sdTBI)
• fludarabine and melphalan (Flu/Mel)
• reduced-intensity fludarabine and busulfan (Flu/Bu2)
• G-CSF from Day -5 through Day -1 per standard of care
• On Day 0, the allograft will be infused per standard of care.
• Azacitidine will be administered on Day +1 and +2 post-stem cell transfusion days
• Cyclophosphamide on Days +3 and +4 post-transplant

Group Type: EXPERIMENTAL

Fludarabine

Intervention Type: DRUG

Fractionated total body irradiation

Intervention Type: RADIATION

Busulfan

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Single dose total body irradiation

Intervention Type: RADIATION

Melphalan

Intervention Type: DRUG

Granulocyte-colony stimulating factor

Intervention Type: DRUG

Stem cell transplant

Intervention Type: PROCEDURE

Azacitidine

Intervention Type: DRUG

Interventions

Fludarabine

Intervention Type: DRUG

Fractionated total body irradiation

Intervention Type: RADIATION

Busulfan

Intervention Type: DRUG

Cyclophosphamide

Intervention Type: DRUG

Single dose total body irradiation

Intervention Type: RADIATION

Melphalan

Intervention Type: DRUG

Granulocyte-colony stimulating factor

Intervention Type: DRUG

Stem cell transplant

Intervention Type: PROCEDURE

Azacitidine

Intervention Type: DRUG

Other Intervention Names

Fludara; 2-Fluoro-ara-A Monophosphate; 2-Fluoro-ara AMP; FAMP; Myerlan; Busulphan; Cytoxan; CPM; CTX; CYT; Alkeran; Phenylalanine mustard; G-CSF; Plerixafor; Mozobil; Neupogen; Filgrastim; Vidaza; Ladakamycin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Schroeder, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

201604081

Identifier Type: -

Identifier Source: org_study_id