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A Phase I Study of the Safety and Feasibility of Azacitidine After Donor Lymphocyte Infusion for Patients With Relapsed Acute Myeloid Leukemia or Myelodysplastic Syndrome After Allogeneic Stem Cell Transplantation

Phase 1
18 Years
Open (Enrolling)
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

Thank you

Trial Information

A Phase I Study of the Safety and Feasibility of Azacitidine After Donor Lymphocyte Infusion for Patients With Relapsed Acute Myeloid Leukemia or Myelodysplastic Syndrome After Allogeneic Stem Cell Transplantation


-To determine the Maximum Tolerated Dose (MTD) of 5-AzaC (azacitidine) when given after
chemotherapy and DLI in patients with AML/MDS who relapse after allogeneic stem cell


- To determine the rate of Grades II-IV and III-IV acute GVHD (aGVHD) in first 100 days
after DLI.

- To determine the rates of complete remission (CR), partial remission, (PR) and complete
remission with incomplete count recovery (CRi), and overall response rate (CR+ CRi +

- To determine overall survival 100 days after DLI.

- To determine the effects of increasing dose of 5-AzaC on frequency and absolute number
of resting regulatory T-cells (rTregs) and activated Tregs (aTregs) at baseline, 7
days, 14 days, 21 days, and ~60 days after first dose of 5-AzaC.


Inclusion Criteria:

- Must have a diagnosis of AML/MDS based on 2008 World Health Organization (WHO)
classification of myeloid malignancies

- Must have laboratory, histologic, or cytogenetic evidence of disease relapse after
allogeneic hematopoietic stem cell transplant (HSCT) and require salvage therapy
followed by DLI

- Must have original donor

- Must have life expectancy >= 2 months

- Must be ≥ 18 years old. Azacitidine is not approved by the FDA for use in children

- Must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 3

- Must have laboratory results indicating:

- Total bilirubin < 2.0 mg/dL

- Aspartate aminotransferase (AST)/alanine aminotransferase (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 5-AzaC 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 (Beta [B]-human chorionic
gonadotropin) within 72 hours prior to initiating therapy and be willing to not
become pregnant by using effective contraception while undergoing treatment and for
at least 3 months afterwards; azacitidine is a pregnancy category D drug and could be
harmful to or cause loss of a fetus; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician

- 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

- Both men and women and members of all races and ethnic groups are eligible for this


Inclusion Criteria:

- Must be the original donor for the allogeneic bone marrow transplant patient

- Must have signed the standard informed consent form; if sufficient cryopreserved
cells remain from a previous donation, no additional donation or consent is required

- Must be eligible according to Washington University "Guidelines for Eligibility of
Normal Donors" or per National Marrow Donor Program (NMDP) standards if unrelated

- Both men and women and members of all races and ethnic groups are eligible for this

PATIENT Exclusion Criteria:

- Must not have Grade III-IV GVHD

- Must not have an advanced malignant hepatic tumor

- Must not receive anti-thymocyte globulin, campath (alemtuzumab) or daclizumab within
4 weeks of DLI

- Must not receive any other forms of chemotherapy after cell infusion during the
treatment protocol

- Must not be receiving any other investigational agents within 14 days of first dose
of study drug

- 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 with azacitidine; these
potential risks may also apply to other agents used in this study

- Must not have a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to azacitidine or other agents used in the study

- Must not have a known or suspected hypersensitivity to azacitidine or mannitol.

- Must not be human immunodeficiency virus (HIV)-positive and on combination
antiretroviral therapy; these patients are ineligible because of the potential for
pharmacokinetic interactions with azacitidine; in addition, these patients are at
increased risk of lethal infections when treated with marrow-suppressive therapy;
appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated

DONOR Exclusion Criteria:

- Must not have any underlying conditions which would contra-indicate apheresis

- Must not be pregnant

Type of Study:


Study Design:

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

Outcome Measure:

MTD and DLT of azacitidine when given after DLI

Outcome Description:

MTD is defined as the maximum dose level immediately below the dose level at which 2 patients of a cohort (3 to 6 patients) experience dose-limiting toxicity during the first cycle.

Outcome Time Frame:

40 days (after DLI)

Safety Issue:


Principal Investigator

Peter Westervelt, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

April 2012

Completion Date:

October 2015

Related Keywords:

  • Leukemia, Myeloid, Acute
  • Myelodysplastic Syndromes
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



Washington University School of MedicineSaint Louis, Missouri  63110