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Phase I/II Trial of Intravenous Azacitidine in Patients Undergoing Matched Unrelated Stem Cell Transplantation

Phase 1/Phase 2
18 Years
65 Years
Open (Enrolling)
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Precursor Cell Lymphoblastic Leukemia-Lymphoma

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Trial Information

Phase I/II Trial of Intravenous Azacitidine in Patients Undergoing Matched Unrelated Stem Cell Transplantation

Inclusion Criteria:

Patients must meet the following criteria within 30 days prior to Day 0 unless otherwise

- Phase I: Diagnosis of any hematological malignancy listed below (excluding
myelofibrosis) in remission or with stable minimal residual disease

- Acute myelogenous leukemia (AML) in 1st or subsequent remission or in relapse
after any remission

- Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission or in relapse
after any remission

- Myelodysplastic syndrome either intermediate 1 or 2, or high risk by the
International Prognostic Scoring System

- Chronic myelogenous leukemia (CML) in accelerated or second chronic phase

- Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater
complete remission, partial remission, or refractory relapse

- Chronic lymphocytic leukemia (CLL), Rai Stage 2-4, failing at least 2 prior

- Multiple myeloma (MM), Stage 2-3

- Myeloproliferative disorder or neoplasm

- Phase II: Diagnosis of AML in remission 1 or 2 or a diagnosis of myelodysplastic
syndrome either intermediate 1 or 2, or high risk by the International Prognostic
Scoring System.

- Patients with MDS must be transplant candidates by current clinical standards.

- Patients who have been treated with hypomethylating agents prior to entering the
study are eligible.

- Must have matched unrelated donor (8 of 8 HLA match at A, B, C, and DR loci) by high
resolution DNA typing

- Must have donor peripheral blood stem cells mobilized by NMDP standards. No bone
marrow donors.

- Must have 2-8 x 10^6 CD34+ cells/kg (recipient weight) infused on Day 0.

- Must have at least one additional aliquot of >1 x 10^6 CD34/kg cryopreserved cells
stored at the time of transplant.

- Must receive a myeloablative or reduced intensity conditioning regimen for SCT as
defined by the CIBMTR

- Cyclophosphamide and single dose total body irradiation

- Fludarabine and busulfan

- Fractionated TBI and cyclophosphamide

- Busulfan and cyclophosphamide

- Must be able to receive GVHD prophylaxis with tacrolimus and methotrexate.

- Must be ≥ 18 yrs old and ≤ 65 yrs old. Azacitidine is not approved by the FDA for
use in children.

- Must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

- Must have laboratory results indicating:

- Total bilirubin < 2.0 mg/dl, unless a diagnosis of Gilbert's disease

- AST/ALT ≤ 3 X the upper limit of institutional normal

- Serum creatinine ≤ 2.0 mg/dl

- Patient must have ability to understand and willingness to provide written informed
consent prior to participation in the study and any related procedures being

- The effects of azacitidine on the developing human fetus at the recommended
therapeutic dose are unknown. For this reason and because category D agents as well
as other therapeutic agents used in this trial are known to be teratogenic, women of
childbearing age must have a negative serum pregnancy test (ß-human chorionic
gonadotropin) within 72 hours prior to initiating the conditioning regimen and be
willing to not become pregnant by using effective contraception while undergoing
treatment and for at least 3 months after the last dose of azacitidine.

- Men must be willing not to father a new child while receiving therapy. They must use
an effective barrier method of contraception during the study and for 3 months
following the last dose.

Exclusion Criteria:

- Must not have myelofibrosis or other disease known to prolong neutrophil engraftment
to > 28 days after transplant.

- Must not be receiving any other investigational agents within 14 days of first dose
of azacitidine (Day 7).

- Must not have myeloablative conditioning as defined below:

- TBI < or = Gy +/- purine analog

- Flu + Cy +/- ATG

- Flu + AraC + Ida

- Cladribine + AraC

- Total Lymphoid Irradiation + ATG

- Must not receive antithymocyte globulin as part of pre-transplant conditioning
regimens. Antithymocyte globulin is excluded due to its potential impact on
modulating the incidence of GvHD or GvL.

- Must not have uncontrolled intercurrent illness including ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or
psychiatric illness/social situations that would limit compliance with study

- Must not be pregnant or breastfeeding. Pregnant women are excluded from this study
because azacitidine is a Category D agent with the potential for teratogenic or
abortifacient effects. Because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with azacitidine,
breastfeeding should be discontinued if the mother is treated azacitidine. These
potential risks may also apply to other agents used in this study.

- Must not have a known or suspected hypersensitivity to azacitidine, mannitol, or
compounds of similar composition to azacitidine..

- Must not have an advanced malignant hepatic tumor.

- Must not be HIV, HBV, or HCV positive.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Phase I: to determine the maximum tolerated dose (MTD) of azacitidine in patients undergoing matched (8 out of 8) unrelated donor transplant for any hematological malignancy in remission or with stable disease.

Outcome Description:

Tolerability of azacitidine will be assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Mark A. Schroeder, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

April 2013

Completion Date:

May 2018

Related Keywords:

  • Leukemia, Myeloid, Acute
  • Myelodysplastic Syndromes
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Lymphoma
  • Myelodysplastic Syndromes
  • Preleukemia



Washington University School of Medicine Saint Louis, Missouri  63110