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

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02756962
• Other study ID #: 201606003
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 6, 2016
• Est. completion date: July 31, 2033

Study information

• Verified date: April 2024
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 107
• Est. completion date: July 31, 2033
• Est. primary completion date: July 31, 2033
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia

Intervention

Drug:
• Cytarabine

Procedure:
• Allogeneic stem cell transplant

• Bone marrow aspiration
Baseline Approximately 30 days after cytotoxic induction therapy End of treatment
• 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.

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

Locations

Country	Name	City	State
United States	University of Florida	Gainesville	Florida
United States	University of Rochester	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Washington University School of Medicine	American Society of Hematology, The Leukemia and Lymphoma Society

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival (OS) of Cohort A compared intermediate risk historical control group	Overall survival is the time from enrollment on study until death from any cause.	Up to 5 years
Secondary	Relapse free survival (RFS) of Cohort B	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	Overall survival (OS) of Cohort B	Overall survival is the time from enrollment on study until death from any cause.	Up to 5 years
Secondary	Compare relapse free survival of Cohort A to Cohort B	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	Compare overall survival of Cohort A to Cohort B	Overall survival is the time from enrollment on study until death from any cause.	Up to 5 years
Secondary	Compare relapse free survival of Cohort A to Cohort B	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.	1 year
Secondary	Compare overall survival of Cohort A to Cohort B	Overall survival is the time from enrollment on study until death from any cause.	1 year
Secondary	Relapse free survival of Cohort B patients who receive alloSCT	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	Overall survival of Cohort B patients who receive alloSCT	Overall survival is the time from enrollment on study until death from any cause.	Up to 5 years
Secondary	Relapse free survival of Cohort B patients who do not receive alloSCT	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	Overall survival of Cohort B patients who do not receive alloSCT	Overall survival is the time from enrollment on study until death from any cause.	Up to 5 years
Secondary	Relapse free survival of patients with a LAM VAF <1.0% treated in Cohort A compared to intermediate risk historical control group	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.	Up to 5 years
Secondary	Overall survival of patients with a LAM VAF <1.0% treated in Cohort A compared to intermediate risk historical control group	--LAM VAF = Leukemia Associated Mutations variant allele frequency; -Overall survival is the time from enrollment on study until death from any cause.	Up to 5 years

External Links

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