Improving Risk Assessment of AML With a Precision Genomic... | NCT02756962

Status Module

Name	Class
The Leukemia and Lymphoma Society	OTHER
American Society of Hematology	OTHER

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort A: HiDAC	Experimental	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.	Drug: Cytarabine Procedure: Bone marrow aspiration Procedure: Punch skin biopsy Device: ClinSeq
Cohort B: Investigator's choice (HiDAC, AlloSCT)	Experimental	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.	Drug: Cytarabine Procedure: Allogeneic stem cell transplant Procedure: Bone marrow aspiration Procedure: Punch skin biopsy Device: ClinSeq

Name	Type	Description	Arm Group Labels	Other Names
Cytarabine	Drug		Cohort A: HiDAC Cohort B: Investigator's choice (HiDAC, AlloSCT)	Ara-C Cytosar-U

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 Outcomes

Measure	Description	Time Frame
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
Relapse free survival (RFS) of Cohort B

Eligibility Module

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.

Facility	Status	City	State	ZIP	Country	Contacts
University of Florida		Gainesville	Florida	32608	United States
Washington University School of Medicine

ID	Term
D007951	Leukemia, Myeloid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases

ID	Term
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D001087	Arabinonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides