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 June 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01687400
First received: September 13, 2012
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

This pilot 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: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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

  • Steady-state plasma decitabine concentration [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    The steady-state plasma decitabine concentration on day 4 +/- 1 will be measured and correlated with clinical overall response.

  • Decrease in bone marrow methylcytosine [ Time Frame: Baseline and Day 10 ] [ Designated as safety issue: No ]
    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
Study Start Date: February 2013
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: April 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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

ONE OF THE FOLLOWING:

  • Patient must have non-M3 AML and be >= 60 years of age OR
  • Non-M3 AML with relapsed disease OR
  • Symptomatic MDS with one of the following:
  • Symptomatic anemia with either hemoglobin < 10.0 g/dL or requiring red blood cell (RBC) transfusion
  • Thrombocytopenia with a history of two or more platelet counts < 50,000/mcL or a significant hemorrhage requiring platelet transfusions
  • Neutropenia with two or more absolute neutrophil count (ANC) < 1,000/mcL

ALL OF THE FOLLOWING:

  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Patient must have > 10% disease burden measured by cytomorphology, flow cytometry, or cytogenetics
  • Peripheral white blood cell count =< 50,000/mcl
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Serum creatinine =< 2.0 x ULN
  • Patient must have undergone =< 2 cycles of prior hypomethylating agent (decitabine or azacitidine)
  • Patient must be enrolled in Human Research Protections Office (HRPO) # 201011766 ("Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases")
  • Patient myst be >= 18 years of age
  • Patient must be able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document

Exclusion Criteria:

  • Patient must not be pregnant or nursing
  • 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 ClinicalTrials.gov identifier: NCT01687400

Contacts
Contact: John Welch, M.D., Ph.D. 314-362-2626 jwelch@dom.wustl.edu

Locations
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      
Sub-Investigator: Timothy Ley, M.D.         
Sub-Investigator: Jeffrey Klco, M.D., Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Welch John, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT01687400     History of Changes
Other Study ID Numbers: 201210102
Study First Received: September 13, 2012
Last Updated: June 30, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 22, 2014