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

This study is currently recruiting participants.
Verified December 2013 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: December 14, 2013
Last verified: December 2013

September 13, 2012
December 14, 2013
February 2013
April 2018   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01687400 on ClinicalTrials.gov Archive Site
  • 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
  • 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 serum decitabine concentration [ Time Frame: Day 4 ] [ Designated as safety issue: No ]
    The steady-state serum 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
Not Provided
Not Provided
 
Genomic Predictors of Decitabine Response in Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
Genomic Predictors of Decitabine Response in AML/MDS

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.

Not Provided
Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Leukemia, Myeloid, Acute
  • Myelodysplastic Syndromes
Drug: decitabine
Other Name: 5-aza-dCyd, 5AZA, DAC, Dacogen, deoxyazacytidine, dezocitidine
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.
Intervention: Drug: decitabine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
125
January 2019
April 2018   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: John Welch, M.D., Ph.D. 314-362-2626 jwelch@dom.wustl.edu
United States
 
NCT01687400
201210102
No
Washington University School of Medicine
Washington University School of Medicine
Not Provided
Principal Investigator: Welch John, M.D., Ph.D. Washington University School of Medicine
Washington University School of Medicine
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP