Clinical trial · Interventional
Improving Risk Assessment of AML With a Precision Genomic Strategy to Assess Mutation Clearance
NCT02756962CI-TRIAL-00096824active not recruitingPhase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Myeloid Leukemia | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
Interventions
Interventions (5)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Allogeneic stem cell transplant | Procedure | — | UNRESOLVED |
| Bone marrow aspiration | Procedure | — | UNRESOLVED |
| ClinSeq | Device | — | UNRESOLVED |
| Cytarabine | Drug | Cytarabine | ALIAS |
| Punch skin biopsy | Procedure | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Cohort A: HiDAC
- description
- * 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.
- interventionNames
- Drug: Cytarabine
- Procedure: Bone marrow aspiration
- Procedure: Punch skin biopsy
- Device: ClinSeq
- type
- EXPERIMENTAL
- label
- Cohort B: Investigator's choice (HiDAC, AlloSCT)
- description
- * 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 60 Years
Show eligibility criteria text
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.References
Publications (1)
- DERIVEDJacoby MA, Spencer DH, Gao F, Uy GL, Burton T, Heath SE, Du F, O'Laughlin M, Fulton RS, Miller CA, Duncavage EJ, Schroeder MA, Ghobadi A, Pusic I, Stockerl-Goldstein KE, Kahl BS, Cashen AF, Christopher MJ, Singh N, Vij R, Crees ZD, Wartman LD, Day RB, Fehniger TA, Oetjen KA, Patel DA, Kim MY, Slade MJ, Ferraro F, Walter MJ, Abboud CN, Abboud R, Link DC, Al-Mansour ZA, Cogle CR, Huselton EJ, DiPersio JF, Westervelt P, Ley TJ. Consolidation Therapy Based on Mutation Clearance in Acute Myeloid Leukemia. NEJM Evid. 2026 Sep;5(9):EVIDoa2500352. doi: 10.1056/EVIDoa2500352. Epub 2026 Aug 25. PMID 42640163