Genomic Predictors of Decitabine Response in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01687400
Recruitment Status : Active, not recruiting
First Posted : September 18, 2012
Last Update Posted : August 22, 2017
Information provided by (Responsible Party):
Washington University School of Medicine

Brief Summary:
This clinical trial studies potential genetic markers which might be used to predict which patients with acute myeloid leukemia or myelodysplastic syndromes respond to decitabine. This study will contribute to the efforts to find effective and less toxic therapies to provide durable remissions in a significant proportion of elderly AML patients.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Myelodysplastic Syndromes Drug: decitabine Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 114 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Genomic Predictors of Decitabine Response in AML/MDS
Actual Study Start Date : February 12, 2013
Actual Primary Completion Date : June 23, 2017
Estimated Study Completion Date : June 23, 2018

Arm Intervention/treatment
Experimental: Decitabine
Patients receive decitabine IV over 1 hour on days 1-10 of a 28-day cycle. Treatment continues for 2 cycles. Patients then receive decitabine IV over 1 hour on days 1-10, 1-5, or 1-3 (depending on response). Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: decitabine
Other Name: 5-aza-dCyd, 5AZA, DAC, Dacogen, deoxyazacytidine, dezocitidine

Primary Outcome Measures :
  1. Correlation of patient specific mutations with overall response rate [ Time Frame: 4 months ]
    Best response after 4 treatment cycles as assessed according to International Working Group (IWG) criteria; bone marrow for gene sequencing will be collected at baseline; mutations will be correlated with overall response and their respective 95% confidence intervals will be provided.

Secondary Outcome Measures :
  1. Compare efficacy of a10-day decitabine per cycle regimen to a 5-day regimen (historical controls) [ Time Frame: 4 months (4 treatment cycles) ]
    Efficacy defined as complete response (complete response [CR]/CR with incomplete blood count recovery [CRi]) and overall response (CR+CRi + partial response [PR]); response assessed according to IWG criteria;

  2. Bone marrow mutation expression profile and change in profile during decitabine treatment [ Time Frame: 60 days ]
    Samples collected at baseline and after 10, 28 and 56 days of therapy; compare the rate of mutation clearance and lowest mutation frequencies between the patients who achieve a CR/CRi after 4 cycles and those who do not

  3. Decrease in bone marrow methylcytosine [ Time Frame: Baseline and Day 10 ]
    Change of total bone marrow deoxyribonucleic acid (DNA) methylcytosine from baseline and its association with both steady-state serum drug levels and response will be assessed using 2-way ANOVA for repeated measurement data

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

All of the following:

  • Patient must have non-M3 AML or MDS
  • An adverse risk karyotype defined by:

    • Complex karyotype by cytogenetics, or
    • Deletion of all or part of chromosome 5, 7, 12, or 17 defined by FISH or cytogenetics, or
    • Somatic TP53 mutation

All of the following:

  1. Patient must have an ECOG performance status ≤ 2.
  2. Patient must have >10% disease burden measured by cytomorphology, flow cytometry, or cytogenetics.
  3. Patient must have peripheral white blood cell count < 50,000/mcl.
  4. Patient must have adequate organ function, defined as:

    1. Total bilirubin < 1.5 x ULN
    2. AST/ALT < 2.5 x ULN
    3. Serum creatinine < 2.0 x ULN
  5. Patient must have undergone ≤ 2 cycles of prior hypomethylating agent (decitabine or azacitidine).
  6. Patient must be enrolled in HRPO# 201011766 ("Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases").
  7. Patient must be > 18 years of age.
  8. Patient must be able to understand and willing to sign an IRB-approved written informed consent document.

Exclusion Criteria:

  • Patient must not be pregnant or nursing
  • Patient must not have acute promyelocytic leukemia or t(15;17) observed by FISH.
  • Patient must not have known central nervous system (CNS) leukemia
  • Patient must not have a history of positive human immunodeficiency virus (HIV) serology
  • Patient must not have a history of positive hepatitis C serology
  • Patient must not have undergone prior allogeneic stem cell transplant
  • Patient must not have any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, ongoing or active graft-versus-host disease (GVHD), congestive heart failure of New York Heart Association (NYHA) class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
  • Patient must not have had radiation therapy within 14 days of enrollment
  • Patient must not have received any chemotherapy within 21 days of enrollment and any acute treatment-related toxicities must have returned to baseline. Patients may be receiving hydrea at time of enrollment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01687400

United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Principal Investigator: Welch John, M.D., Ph.D. Washington University School of Medicine

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Washington University School of Medicine Identifier: NCT01687400     History of Changes
Other Study ID Numbers: 201210102
First Posted: September 18, 2012    Key Record Dates
Last Update Posted: August 22, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors