Clinical trial NCT03013998: Study of Biomarker-Based Treatment of Acute Myeloid Leukemia
Official title: A Master Protocol for Biomarker-Based Treatment of AML (The Beat AML Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Previously Untreated Relapsed Refractory Acute Myeloid Leukemia
Keywords: SNDX-5613
ZE46-0134
Lead sponsor: Beat AML, LLC
Sponsor class: OTHER
First posted: 2017-01-09
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This screening and multi-sub-study Phase 1b/2 trial will establish a method for genomic screening followed by assigning and accruing simultaneously to a multi-study "Master Protocol (BAML-16-001-M1)." The specific subtype of acute myeloid leukemia will determine which sub-study, within this protocol, a participant will be assigned to evaluate investigational therapies or combinations with the ultimate goal of advancing new targeted therapies for approval. The study also includes a marker negative sub-study which will include all screened patients not eligible for any of the biomarker-driven sub-studies.


Eligibility criteria: Inclusion Criteria:

* Adults, age 60 years or older at the time of diagnosis unless in a specific known cytogenetic and genomic group for which treatment in Group A or B is allowed by the sub-study where age 18 and older is allowed. Patients \< 60 years old who are screened but do not fall within the cytogenetic and genomic open sub-studies would still be followed on the Master Protocol and not considered screen fails.
* Subjects must be able to understand and provide written informed consent
* Cohort Inclusion Criteria - Group A: Subjects must have previously untreated acute myeloid leukemia (AML) according to the WHO classification with no prior treatment other than hydroxyurea. Subjects with blasts % in bone marrow of 10% to 19% or blasts in blood of 10% to 19% will be allowed to enroll to this group. For previously untreated subjects with ≥ 20% blasts in bone marrow or blood only: Prior therapy for myelodysplastic syndrome (MDS), myeloproliferative syndromes (MPD), or aplastic anemia is permitted but not with hypomethylating agents.
* Cohort Inclusion Criteria - Group B: Subjects must have relapsed or refractory AML according to the WHO classification. For study purposes, refractory AML is defined as failure to ever achieve CR or recurrence of AML within 6 months of achieving CR; relapsed AML is defined as all others with disease after prior remission. For select genomic aberrations specified in the studies, patients ≥ 18 years of age may be allowed to enroll in this portion of the study.

Exclusion Criteria:

* Isolated myeloid sarcoma (meaning, patients must have blood or marrow involvement with AML or involved with 10% to 19% blasts to enter the study)
* Acute promyelocytic leukemia
* Symptomatic central nervous system (CNS) involvement by AML
* Signs of leukostasis requiring urgent therapy
* Disseminated intravascular coagulopathy with active bleeding or signs of thrombosis
* Patients with psychological, familial, social, or geographic factors that otherwise preclude them from giving informed consent, following the protocol, or potentially hamper compliance with study treatment and follow-up
* Any other significant medical condition, including psychiatric illness or laboratory abnormality, that would preclude the patient participating in the trial or would confound the interpretation of the results of the trial

Primary outcomes:
measure: Proportion of patients for whom molecular, immunophenotypic, and/or biochemical studies are completed in < 7 calendar days for assignment of treatment
timeFrame: 7 days
measure: Proportion of patients assigned to a novel therapeutic treatment group in 1 of several sub-studies in this Master Protocol, based on the result of the molecular, immunophenotypic, and/or biochemical studies
timeFrame: 7 days
measure: Clinical response rate (rate of complete and partial responses) according to International Working Group criteria for treatment outcomes in therapeutic trials in acute myeloid leukemia
timeFrame: Up to 5 years
Secondary outcomes:
measure: Proportion of patients enrolled on this trial that ultimately will be assigned and go onto an assigned therapy
timeFrame: 7 days
measure: Dynamic changes in clonal architecture over time in acute myeloid leukemia patients receiving targeted therapies
timeFrame: time of diagnosis, remission (complete response or complete response with incomplete blood count recovery), 1 year of treatment, and relapse
measure: Relationships between baseline functional status and response rate or progression-free survival based on graphical comparison (eg, side-by-side boxplots or Kaplan-Meier plots)
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Los Angeles
country: United States
facility: UCLA Ronald Reagan Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida Health Shands Cancer Hospital
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Fairway
country: United States
facility: University of Kansas Clinical Research Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic Minnesota
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Hospitals, University of North Carolina at Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute, University of Utah
state: Utah
Study officials:
affiliation: Beat AML
name: John C Byrd, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Burd A, Levine RL, Ruppert AS, Mims AS, Borate U, Stein EM, Patel P, Baer MR, Stock W, Deininger M, Blum W, Schiller G, Olin R, Litzow M, Foran J, Lin TL, Ball B, Boyiadzis M, Traer E, Odenike O, Arellano M, Walker A, Duong VH, Kovacsovics T, Collins R, Shoben AB, Heerema NA, Foster MC, Vergilio JA, Brennan T, Vietz C, Severson E, Miller M, Rosenberg L, Marcus S, Yocum A, Chen T, Stefanos M, Druker B, Byrd JC. Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial. Nat Med. 2020 Dec;26(12):1852-1858. doi: 10.1038/s41591-020-1089-8. Epub 2020 Oct 26.
citation: Borate U, Yang F, Press R, Ruppert AS, Jones D, Caruthers S, Zhao W, Vergilio JA, Pavlick DC, Juckett L, Norris B, Bucy T, Burd A, Stein EM, Patel P, Baer MR, Stock W, Schiller G, Blum W, Kovacsovics T, Litzow M, Foran J, Heerema NA, Rosenberg L, Marcus S, Yocum A, Stefanos M, Druker B, Byrd JC, Levine RL, Mims A. Samples from patients with AML show high concordance in detection of mutations by NGS at local institutions vs central laboratories. Blood Adv. 2023 Oct 24;7(20):6048-6054. doi: 10.1182/bloodadvances.2022009008.
citation: Rosenberg L, Levaux H, Levine RL, Shah A, Denmark J, Hereema N, Owen M, Kalk S, Kenny N, Vinson G, Vergilio JA, Mims A, Borate U, Blum W, Stein E, Gana TJ, Stefanos M, Yocum A, Marcus S, Shoben A, Druker B, Byrd J, Burd A. Streamlined Operational Approaches and Use of e-Technologies in Clinical Trials: Beat Acute Myeloid Leukemia Master Trial. Ther Innov Regul Sci. 2021 Sep;55(5):926-935. doi: 10.1007/s43441-021-00277-w. Epub 2021 May 16.
citation: Cai SF, Huang Y, Lance JR, Mao HC, Dunbar AJ, McNulty SN, Druley T, Li Y, Baer MR, Stock W, Kovacsovics T, Blum WG, Schiller GJ, Olin RL, Foran JM, Litzow M, Lin T, Patel P, Foster MC, Boyiadzis M, Collins RH, Chervin J, Shoben A, Vergilio JA, Heerema NA, Rosenberg L, Chen TL, Yocum AO, Druggan F, Marcus S, Stefanos M, Druker BJ, Mims AS, Borate U, Burd A, Byrd JC, Levine RL, Stein EM. A study to assess the efficacy of enasidenib and risk-adapted addition of azacitidine in newly diagnosed IDH2-mutant AML. Blood Adv. 2024 Jan 23;8(2):429-440. doi: 10.1182/bloodadvances.2023010563.
citation: Duong VH, Ruppert AS, Mims AS, Borate U, Stein EM, Baer MR, Stock W, Kovacsovics T, Blum W, Arellano ML, Schiller GJ, Olin RL, Foran JM, Litzow MR, Lin TL, Patel PA, Foster MC, Redner RL, Al-Mansour Z, Cogle CR, Swords RT, Collins RH, Vergilio JA, Heerema NA, Rosenberg L, Yocum AO, Marcus S, Chen T, Druggan F, Stefanos M, Gana TJ, Shoben AB, Druker BJ, Burd A, Byrd JC, Levine RL, Boyiadzis MM. Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial. Cancer. 2023 Aug 1;129(15):2308-2320. doi: 10.1002/cncr.34780. Epub 2023 Apr 20.
citation: Saliba AN, Kaufmann SH, Stein EM, Patel PA, Baer MR, Stock W, Deininger M, Blum W, Schiller GJ, Olin RL, Litzow MR, Lin TL, Ball BJ, Boyiadzis MM, Traer E, Odenike O, Arellano ML, Walker A, Duong VH, Kovacsovics T, Collins RH, Shoben AB, Heerema NA, Foster MC, Peterson KL, Schneider PA, Martycz M, Gana TJ, Rosenberg L, Marcus S, Yocum AO, Chen T, Stefanos M, Mims AS, Borate U, Burd A, Druker BJ, Levine RL, Byrd JC, Foran JM. Pevonedistat with azacitidine in older patients with TP53-mutated AML: a phase 2 study with laboratory correlates. Blood Adv. 2023 Jun 13;7(11):2360-2363. doi: 10.1182/bloodadvances.2022008625. No abstract available.