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Trial record 1 of 1 for:    NCT01687400
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Genomic Predictors of Decitabine Response in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by Washington University School of Medicine
Information provided by (Responsible Party):
Washington University School of Medicine Identifier:
First received: September 13, 2012
Last updated: January 26, 2017
Last verified: January 2017
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 Intervention Phase
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Drug: decitabine
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Genomic Predictors of Decitabine Response in AML/MDS

Resource links provided by NLM:

Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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:
  • 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;

  • 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

  • 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

Estimated Enrollment: 125
Actual Study Start Date: February 12, 2013
Estimated Study Completion Date: April 30, 2018
Estimated Primary Completion Date: April 30, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01687400

Contact: John Welch, M.D., Ph.D. 314-362-2626

United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: John Welch, M.D., Ph.D.    314-362-2626   
Principal Investigator: John Welch, M.D, Ph.D.         
Sub-Investigator: Eric Duncavage, M.D.         
Sub-Investigator: Timothy Ley, M.D.         
Sponsors and Collaborators
Washington University School of Medicine
Principal Investigator: Welch John, M.D., Ph.D. Washington University School of Medicine
  More Information

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
Study First Received: September 13, 2012
Last Updated: January 26, 2017
Individual Participant Data  
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 processed this record on April 21, 2017