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NCT Number: NCT02756962

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Acute Myeloid Leukemia Hematologic Diseases Hemic and Lymphatic Diseases Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Neoplasms Neoplasms by Histologic Type

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Florida, Gainesville, Florida, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Cytarabine

Drug

Other names: Ara-C, Cytosar-U, Tarabine-PFS, AraC

Allogeneic stem cell transplant

Procedure

Other names: AlloSCT

Bone Marrow Aspiration

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

punch skin biopsy

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

Device

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

Primary outcomes

  1. Relapse free survival of Cohort A compared to intermediate risk historical control group

    Time frame: Up to 5 years

    • 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.

Secondary outcomes

  1. Overall survival (OS) of Cohort A compared intermediate risk historical control group

    Time frame: Up to 5 years

    Overall survival is the time from enrollment on study until death from any cause.

  2. Relapse free survival (RFS) of Cohort B

    Time frame: Up to 5 years

    • 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.

  3. Overall survival (OS) of Cohort B

    Time frame: Up to 5 years

    Overall survival is the time from enrollment on study until death from any cause.

  4. Compare relapse free survival of Cohort A to Cohort B

    Time frame: Up to 5 years

    • 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.

  5. Compare overall survival of Cohort A to Cohort B

    Time frame: Up to 5 years

    Overall survival is the time from enrollment on study until death from any cause.

  6. Compare relapse free survival of Cohort A to Cohort B

    Time frame: 1 year

    • 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.

  7. Compare overall survival of Cohort A to Cohort B

    Time frame: 1 year

    Overall survival is the time from enrollment on study until death from any cause.

  8. Relapse free survival of Cohort B patients who receive alloSCT

    Time frame: Up to 5 years

    • 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.

  9. Overall survival of Cohort B patients who receive alloSCT

    Time frame: Up to 5 years

    Overall survival is the time from enrollment on study until death from any cause.

  10. Relapse free survival of Cohort B patients who do not receive alloSCT

    Time frame: Up to 5 years

    • 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.

  11. Overall survival of Cohort B patients who do not receive alloSCT

    Time frame: Up to 5 years

    Overall survival is the time from enrollment on study until death from any cause.

  12. Relapse free survival of patients with a LAM VAF <1.0% treated in Cohort A compared to intermediate risk historical control group

    Time frame: Up to 5 years

    • LAM VAF = Leukemia Associated Mutations variant allele frequency
    • 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.

  13. Overall survival of patients with a LAM VAF <1.0% treated in Cohort A compared to intermediate risk historical control group

    Time frame: Up to 5 years

    --LAM VAF = Leukemia Associated Mutations variant allele frequency

    -Overall survival is the time from enrollment on study until death from any cause.

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • American Society of Hematology
  • The Leukemia and Lymphoma Society

Registry information

Important dates

Study start
2016
Primary completion
2029
Study completion
2029
First posted
Apr 29, 2016
Registry last updated
Oct 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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