Back to results

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

Primary Purpose

Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

decitabine

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Acute

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

Patient must have an ECOG performance status ≤ 2.
Patient must have >10% disease burden measured by cytomorphology, flow cytometry, or cytogenetics.
Patient must have peripheral white blood cell count < 50,000/mcl.
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
Patient must have undergone ≤ 2 cycles of prior hypomethylating agent (decitabine or azacitidine).
Patient must be enrolled in HRPO# 201011766 ("Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases").
Patient must be > 18 years of age.
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.

Sites / Locations

Washington University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Decitabine

Arm Description

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.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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.

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 .

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

Change in Bone Marrow Methylcytosine

-Change of total bone marrow deoxyribonucleic acid (DNA) methylcytosine from baseline to Day 10

Full Information

NCT ID

NCT01687400

First Posted

September 13, 2012

Last Updated

September 5, 2018

Sponsor

Washington University School of Medicine

1. Study Identification

Unique Protocol Identification Number

NCT01687400

Brief Title

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

Official Title

Genomic Predictors of Decitabine Response in AML/MDS

Study Type

Interventional

2. Study Status

Record Verification Date

September 2018

Overall Recruitment Status

Completed

Study Start Date

February 12, 2013 (Actual)

Primary Completion Date

June 23, 2017 (Actual)

Study Completion Date

November 13, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

114 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Decitabine

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

decitabine

Other Intervention Name(s)

5-aza-dCyd, 5AZA, DAC, Dacogen, deoxyazacytidine, dezocitidine

Primary Outcome Measure Information:

Title

Correlation of Patient Specific Mutations With Overall Response Rate

Description

Time Frame

4 months (4 treatment cycles)

Secondary Outcome Measure Information:

Title

Compare Outcomes of a 10-day Decitabine Per Cycle Regimen to a 5-day Regimen (Historical Controls)

Description

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.

Time Frame

4 months (4 treatment cycles)

Title

Rate of Mutation Clearance During Treatment

Description

Time Frame

Up to Day 56

Title

Peripheral Blood Decitabine Plasma Levels

Description

Time Frame

Day 4

Title

Change in Bone Marrow Methylcytosine

Description

-Change of total bone marrow deoxyribonucleic acid (DNA) methylcytosine from baseline to Day 10

Time Frame

Baseline and Day 10

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: Patient must have an ECOG performance status ≤ 2. Patient must have >10% disease burden measured by cytomorphology, flow cytometry, or cytogenetics. Patient must have peripheral white blood cell count < 50,000/mcl. Patient must have adequate organ function, defined as: Total bilirubin < 1.5 x ULN AST/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 HRPO# 201011766 ("Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases"). Patient must be > 18 years of age. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Welch John, M.D., Ph.D.

Organizational Affiliation

Washington University School of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Washington University School of Medicine

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

27959731

Citation

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. doi: 10.1056/NEJMoa1605949.

Results Reference

derived

Links:

URL

http://www.siteman.wustl.edu

Description

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

Learn more about this trial

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

We'll reach out to this number within 24 hrs