Clinical trial NCT02756962: Improving Risk Assessment of AML With a Precision Genomic Strategy to Assess Mutation Clearance
Official title: Improving Risk Assessment of AML With a Precision Genomic Strategy to Assess Mutation Clearance
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: The Leukemia and Lymphoma Society
name: American Society of Hematology
First posted: 2016-04-29
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Relapse free survival of Cohort A compared to intermediate risk historical control group
timeFrame: Up to 5 years
Secondary outcomes:
measure: Overall survival (OS) of Cohort A compared intermediate risk historical control group
timeFrame: Up to 5 years
measure: Relapse free survival (RFS) of Cohort B
timeFrame: Up to 5 years
measure: Overall survival (OS) of Cohort B
timeFrame: Up to 5 years
measure: Compare relapse free survival of Cohort A to Cohort B
timeFrame: Up to 5 years
measure: Compare overall survival of Cohort A to Cohort B
timeFrame: Up to 5 years
measure: Compare relapse free survival of Cohort A to Cohort B
timeFrame: 1 year
measure: Compare overall survival of Cohort A to Cohort B
timeFrame: 1 year
measure: Relapse free survival of Cohort B patients who receive alloSCT
timeFrame: Up to 5 years
measure: Overall survival of Cohort B patients who receive alloSCT
timeFrame: Up to 5 years
measure: Relapse free survival of Cohort B patients who do not receive alloSCT
timeFrame: Up to 5 years
measure: Overall survival of Cohort B patients who do not receive alloSCT
timeFrame: Up to 5 years
measure: Relapse free survival of patients with a LAM VAF <1.0% treated in Cohort A compared to intermediate risk historical control group
timeFrame: Up to 5 years
measure: Overall survival of patients with a LAM VAF <1.0% treated in Cohort A compared to intermediate risk historical control group
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Rochester
country: United States
facility: University of Rochester
state: New York
Study officials:
affiliation: Washington University School of Medicine
name: Meagan Jacoby, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: