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

Myelodysplastic Syndromes Clinical Trial

Official title:

Genomic Predictors of Decitabine Response in AML/MDS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01687400
• Other study ID #: 201210102
• Status: Completed
• Phase: Phase 2
• Start date: February 12, 2013
• Est. completion date: November 13, 2017

Study information

• Verified date: September 2018
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: November 13, 2017
• Est. primary completion date: June 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• decitabine

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of Patient Specific Mutations With Overall Response Rate	-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 rate; --Complete remission (CR), Complete remission with incomplete hematologic recovery (CRi), Marrow complete remission (mCR), Partial remission (PR), Stable disease (SD), Progressive disease (PD)	4 months (4 treatment cycles)
Secondary	Compare Outcomes of a 10-day Decitabine Per Cycle Regimen to a 5-day Regimen (Historical Controls)	The overall response rate (CR/CRi/mCR/PR) and complete response rate (CR/CRi/mCR) will be compared with historical controls. Response assessed according to IWG criteria.	4 months (4 treatment cycles)
Secondary	Rate of Mutation Clearance During Treatment	Samples collected at baseline and after 10, 28 and 56 days of therapy; the rate of mutation clearance was measured as mean VAF change per day of treatment and was estimated using linear mixed model for repeated measurement data .	Up to Day 56
Secondary	Peripheral Blood Decitabine Plasma Levels	To determine whether steady state serum concentrations of decitabine correlated with responses; Complete remission (CR), Complete remission with incomplete hematologic recovery (CRi), Partial remission (PR), Stable disease (SD), Progressive disease (PD), Not applicable (NA) - assessed according to International Working Group (IWG) criteria	Day 4
Secondary	Change in Bone Marrow Methylcytosine	-Change of total bone marrow deoxyribonucleic acid (DNA) methylcytosine from baseline to Day 10	Baseline and Day 10

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine