Improving Risk Assessment of AML With a Precision Genomic Strategy to Assess Mutation Clearance

NCT ID: NCT02756962

Last Updated: 2025-10-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 107 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-06
• Study Completion Date: 2029-07-31

Brief Summary

The investigators will prospectively determine whether the relapse-free and overall survival in patients who have cleared their leukemia-associated mutations treated with standard consolidation chemotherapy is superior to what is expected based on historical controls. The investigators will also prospectively determine the relapse-free and overall survival of patients who have not cleared their mutations. Because the relapse rate of patients with persistent mutations is expected to be high, treatment with either standard of care consolidation therapy alone or alloSCT will be permitted, at the discretion of the treating physician.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort A: HiDAC

• At the time of diagnostic bone marrow biopsy, samples will be clinically sequenced via ClinSeq
• Patients who have clearance of their leukemia-associated mutations, defined as a LAM VAF <2.5% will be assigned to the high-dose cytarabine consolidation (HiDAC) arm.
• HiDAC = Standard regimen of cytarabine 1.5 g/m^2 or 3 g/m^2 over 2-3 hours twice a day on Days 1, 3, & 5 of each 28 day cycle for 3-4 cycles. Can be replaced by Onureg with permission from PI.
• For patients with the FLT3-ITD or a FLT3-TKD mutation, therapy with the FDA-approved FLT3 inhibitor midostaurin is permitted at the discretion of the treating physician.

Group Type: EXPERIMENTAL

Cytarabine

Intervention Type: DRUG

Bone marrow aspiration

Intervention Type: PROCEDURE

• Baseline
• Approximately 30 days after cytotoxic induction therapy
• End of treatment

Punch skin biopsy

Intervention Type: PROCEDURE

• The first will be obtained with the initial blood and bone marrow collections, whenever possible.
• The second will be obtained at the time of re-biopsy to confirm remission.

ClinSeq

Intervention Type: DEVICE

Clinical Sequencing to determine clearance or persistence of leukemia-associate mutations performed at MGI CLIA lab

Cohort B: Investigator's choice (HiDAC, AlloSCT)

• At the time of diagnostic bone marrow biopsy, samples will be clinically sequenced via ClinSeq
• Patients who have persistent leukemia-associated mutations, defined as a LAM VAF ≥2.5% will be assigned to the investigator's choice arm.
• Patients assigned to this arm may received either HiDAC or AlloSCT.
• HiDAC = Standard regimen of cytarabine 1.5 g/m^2 or 3 g/m^2 over 2-3 hours twice a day on Days 1, 3, & 5 of each 28 day cycle for 3-4 cycles. Can be replaced by Onureg with permission from PI.
• The source of stem cell product, donor selection, conditioning regimen, graft-versus-host-prophylaxis, and supportive care will be at the discretion of the treatment physician
• For patients with the FLT3-ITD or a FLT3-TKD mutation, therapy with the FDA-approved FLT3 inhibitor midostaurin is permitted at the discretion of the treating physician.

Group Type: EXPERIMENTAL

Cytarabine

Intervention Type: DRUG

Allogeneic stem cell transplant

Intervention Type: PROCEDURE

Bone marrow aspiration

Intervention Type: PROCEDURE

• Baseline
• Approximately 30 days after cytotoxic induction therapy
• End of treatment

Punch skin biopsy

Intervention Type: PROCEDURE

• The first will be obtained with the initial blood and bone marrow collections, whenever possible.
• The second will be obtained at the time of re-biopsy to confirm remission.

ClinSeq

Intervention Type: DEVICE

Clinical Sequencing to determine clearance or persistence of leukemia-associate mutations performed at MGI CLIA lab

Interventions

Cytarabine

Intervention Type: DRUG

Allogeneic stem cell transplant

Intervention Type: PROCEDURE

Bone marrow aspiration

• Baseline
• Approximately 30 days after cytotoxic induction therapy
• End of treatment

Intervention Type: PROCEDURE

Punch skin biopsy

• The first will be obtained with the initial blood and bone marrow collections, whenever possible.
• The second will be obtained at the time of re-biopsy to confirm remission.

Intervention Type: PROCEDURE

ClinSeq

Clinical Sequencing to determine clearance or persistence of leukemia-associate mutations performed at MGI CLIA lab

Intervention Type: DEVICE

Other Intervention Names

Ara-C; Cytosar-U; Tarabine-PFS; AraC; AlloSCT

Eligibility Criteria

Inclusion Criteria

• Age 18-60 years.
• Considered to be suitable intensive (cytotoxic) induction candidates.
• Has previously untreated, de novo, non-M3 AML with intermediate-risk disease (Intermediate-I or Intermediate-II) as defined by ELN criteria OR normal cytogenetics with mutated NPM1 without FLT3-ITD. Monoallelic CEBPA mutations are not considered favorable risk and are therefore eligible.
• Has undergone cytotoxic induction therapy
• In a morphologic complete remission with incomplete blood count recovery, or morphologic complete remission post-induction after no more than 2 induction cycles as defined by revised IWG criteria
• Patients at Washington University must be enrolled in HRPO# 201011766 ("Tissue Acquisition for Analysis of Genetic Progression Factors in Hematologic Diseases").This is not a requirement for secondary sites. However, secondary sites must provide informed consent forms that document that permission for whole genome, whole exome, and/or genome wide sequencing, and data sharing among institutions, was obtained. Because we will be also be sequencing non-diseased (normal) tissue, the informed consent forms must explicitly ask if patients wish to be informed, (or in the case of their death, their next-of-kin) if a deleterious mutation is identified in their non-diseased tissue, as this may be heritable.
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Able to understand and willing to sign an IRB approved written informed consent document.
• Willing to comply with the treatment assignment:

• Intent to proceed with HiDAC consolidation for LAM VAF <2.5%
• Intent to proceed with either HiDAC consolidation or allogeneic stem cell transplantation, at the discretion of the treating physician, for LAM ≥2.5%

Exclusion Criteria

• Diagnosis acute promyelocytic leukemia (APL) with t(15;17)(q22;q12); PML-RARA.
• Therapy-related AML (defined as occurrence of AML due to prior exposure to chemotherapy or radiation for malignancy).
• Secondary AML (defined as development of AML in patients with an antecedent hematological malignancy).
• Has a medical or psychosocial conditions that would prevent study compliance.
• Known seropositivity for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B vaccine are eligible.
• History of allergic reaction to compounds of similar chemical or biologic composition to cytarabine.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 3 days of signing consent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Leukemia and Lymphoma Society

OTHER

Sponsor Role: collaborator

American Society of Hematology

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Meagan Jacoby, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

University of Florida

Gainesville, Florida, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of Rochester

Rochester, New York, United States

Countries

United States

Related Links

http://siteman.wustl.edu

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

Other Identifiers

201606003

Identifier Type: -

Identifier Source: org_study_id