Protocol Summary

Protocol No.: OCR18848

Sponsor Protocol No.: 201606003

Protocol Title.: Improving Risk Assessment of AML With a Precision Genomic Strategy to Assess Mutation Clearance

Principal Investigator: Cogle, Christopher

Objective: 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.

Phase: Phase II

Age Group: Adult

Age: 18 Years - 60 Years

Gender: All

Scope: National

Treatment:

Experimental: Cohort A: HiDAC
At the time of diagnostic bone marrow biopsy, samples will be clinically sequenced 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. 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.

Experimental: Cohort B: Investigator's choice (HiDAC, AlloSCT)
At the time of diagnostic bone marrow biopsy, samples will be clinically sequenced 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. 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.

Detailed Eligibility:

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.

Applicable Conditions:

  • Leukemia
  • Participation Institution:

  • UF Gainesville : Emma Rosenau
  • Contact:
    Emma Rosenau
    Phone: +1 352-294-8938
    Email: roseeg@ufl.edu

    More Information: View study listing on ClinicialTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT02756962