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

NCT ID: NCT01687400

Last Updated: 2018-10-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-12
• Study Completion Date: 2017-11-13

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.

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

decitabine

Intervention Type: DRUG

Interventions

decitabine

Intervention Type: DRUG

Other Intervention Names

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

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:

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

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

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 27959731 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.siteman.wustl.edu

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

Other Identifiers

201210102

Identifier Type: -

Identifier Source: org_study_id