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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
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT01687400
First received: September 13, 2012
Last updated: January 26, 2017
Last verified: January 2017

September 13, 2012
January 26, 2017
February 12, 2013
April 30, 2018   (Final data collection date for primary outcome measure)
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.
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) ]
    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
  • 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
  • Steady-state serum decitabine concentration [ Time Frame: Day 4 ]
    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 ]
    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 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
Intervention Model: Single Group Assignment
Masking: No masking
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
Welch JS, Petti AA, Miller CA, Fronick CC, O'Laughlin M, Fulton RS, Wilson RK, Baty JD, Duncavage EJ, Tandon B, Lee YS, Wartman LD, Uy GL, Ghobadi A, Tomasson MH, Pusic I, Romee R, Fehniger TA, Stockerl-Goldstein KE, Vij R, Oh ST, Abboud CN, Cashen AF, Schroeder MA, Jacoby MA, Heath SE, Luber K, Janke MR, Hantel A, Khan N, Sukhanova MJ, Knoebel RW, Stock W, Graubert TA, Walter MJ, Westervelt P, Link DC, DiPersio JF, Ley TJ. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. N Engl J Med. 2016 Nov 24;375(21):2023-2036.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
125
April 30, 2018
April 30, 2018   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact: John Welch, M.D., Ph.D. 314-362-2626 jwelch@wustl.edu
United States
 
 
NCT01687400
201210102
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
No
Not Provided
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
January 2017

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