Improving Risk Assessment of AML With a Precision Genomic Strategy to Assess Mutation Clearance
1 other identifier
interventional
107
1 country
3
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2016
Longer than P75 for phase_2
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 27, 2016
CompletedFirst Posted
Study publicly available on registry
April 29, 2016
CompletedStudy Start
First participant enrolled
July 6, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 31, 2029
October 28, 2025
October 1, 2025
13.1 years
April 27, 2016
October 26, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Relapse free survival of Cohort A compared to intermediate risk historical control group
* Relapse-free survival is the time from study enrollment (morphologic complete remission (CR) or morphologic complete remission with incomplete blood count recovery (CRi) is required) until documented disease relapse, or death from any cause. * CR=Defined as morphologic leukemia-free state, defined as less than 5% blasts in aspirate with marrow spicules and a count of ≥200 nucleated cells and no blasts with Auer rods or any persistence of extramedullary disease. In addition, ANC \>1000/μl and platelet count of ≥100,000/μl. Patient must be independent of transfusions. No duration requirement for this designation. * CRi=Defined as morphologic complete recovery with the exception of neutropenia \<1000/μl or thrombocytopenia \<100,000/μl.
Up to 5 years
Secondary Outcomes (13)
Overall survival (OS) of Cohort A compared intermediate risk historical control group
Up to 5 years
Relapse free survival (RFS) of Cohort B
Up to 5 years
Overall survival (OS) of Cohort B
Up to 5 years
Compare relapse free survival of Cohort A to Cohort B
Up to 5 years
Compare overall survival of Cohort A to Cohort B
Up to 5 years
- +8 more secondary outcomes
Study Arms (2)
Cohort A: HiDAC
EXPERIMENTAL* 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.
Cohort B: Investigator's choice (HiDAC, AlloSCT)
EXPERIMENTAL* 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.
Interventions
* Baseline * Approximately 30 days after cytotoxic induction therapy * End of treatment
* 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.
Clinical Sequencing to determine clearance or persistence of leukemia-associate mutations performed at MGI CLIA lab
Eligibility Criteria
You may qualify if:
- 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%
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Washington University School of Medicinelead
- The Leukemia and Lymphoma Societycollaborator
- American Society of Hematologycollaborator
Study Sites (3)
University of Florida
Gainesville, Florida, 32608, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
University of Rochester
Rochester, New York, 14642, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Meagan Jacoby, M.D., Ph.D.
Washington University School of Medicine
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 27, 2016
First Posted
April 29, 2016
Study Start
July 6, 2016
Primary Completion (Estimated)
July 31, 2029
Study Completion (Estimated)
July 31, 2029
Last Updated
October 28, 2025
Record last verified: 2025-10
Data Sharing
- IPD Sharing
- Will not share