Session: 617. Acute Myeloid Leukemias: Commercially Available Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Clinical Research
Study Design and Methods: This protocol, supported by the Leukemia and Lymphoma Society, is a sub-study of the Beat AML Master Trial (NCT03013998) in which untreated AML patients age ≥ 60 are assigned an investigational therapy based on cytogenetic and central genomic analysis. Patients are randomized onto Arm A (28-day Ven-Aza schedule) or Arm B (14-day Ven-Aza schedule) stratified by age (60-74 vs. 75+ years). The primary objective is to determine the complete remission (CR) rate of patients treated in each randomized arm for up to 2 cycles. The secondary objectives will include assessments of composite complete remission (CR, CR with hematologic improvement, CR with incomplete count recovery), duration of remission, survival, and incidence of treatment-related and non-related toxicities. Additionally, the overall incidence of febrile neutropenia, grade ≥3 infections, transfusions, days of hospitalization and time to neutrophil recovery will be determined.
In both arms of the study, patients will be assessed for response at day 21-28 of cycles 1 and 2. Patients who have marrow remission (< 5% blasts) will wait for count recovery of absolute neutrophil count ≥ 1.0x109/L and platelets ≥ 100x109/L before initiating the next cycle of therapy. Patients will then be followed for survival. With the exception of the Ven dosing schedule (14 vs. 28 days), the FDA approved package insert for Ven, including dose modifications for concurrent azole therapy, will be followed in both arms.
The intent of the analysis is to demonstrate that the 14-day Ven-Aza regimen is at least as effective as the standard 28-day regimen. A two-part design with total of 166 patients (83 per group) will provide 80% power to detect a 10% non-inferiority margin at the one-sided 5% significance level, assuming that the CR rate is 36% for the 28-day regimen, as observed in VIALE-A, and 25% higher (45%) for the 14-day regimen. In addition to assessing the frequency of adverse events such as cytopenias, safety monitoring will include an assessment of response rates after at least 25% of patients have completed 2 cycles of treatment, with consideration for stopping the study if data suggest the 14-day regimen is inferior to the standard regimen. The study has now expanded and will fully enroll all 166 patients.
Disclosures: Borate: Daiichi Sankyo: Consultancy; Sumitomo: Consultancy; Abbvie: Consultancy; Incyte: Consultancy; Astellas: Consultancy; Rigel: Consultancy; BMS: Consultancy; Vincerx Pharma: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: IDMC; Novartis: Consultancy. Zeidner: Sumitomo Pharma: Consultancy, Research Funding; Stemline: Research Funding; Shattuck Labs: Consultancy, Research Funding; Servier: Consultancy; Sellas Life Sciences: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Newave: Research Funding; Merck: Research Funding; Loxo: Research Funding; Jazz: Research Funding; Gilead: Consultancy, Research Funding; Genmab: Consultancy; Foghorn: Consultancy; Faron: Research Funding; Daiichi Sankyo: Consultancy; AstraZeneca: Research Funding; Astex: Research Funding; Arog: Research Funding; Akeso Biopharma: Research Funding; AbbVie: Consultancy, Research Funding; Syndax: Consultancy; Takeda: Research Funding; Zentalis: Research Funding. Swords: Disc Medicine: Consultancy. Stein: Genentech: Consultancy, Other: consulting fees; Abbvie: Consultancy, Other: consulting fees; Gilead: Consultancy, Other: consulting fees; Astellas Pharmaceuticals: Consultancy, Other: consulting fees; Daiichi Sankyo, Inc.: Consultancy, Other: consulting fees; Servier: Consultancy, Other: consulting fees; Agios Pharmaceuticals: Consultancy, Other: consulting fees; Jazz Pharmaceuticals: Consultancy, Other: consulting fees; Celgene: Consultancy, Other: consulting fees; AstraZeneca: Consultancy, Other: consulting fees. Stock: Adaptive: Consultancy, Honoraria; Kura: Research Funding; Kura, Servier, Newave, Adaptive, Jazz, Asofarma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Madanat: Blueprint Medicines, MD Education, and Morphosys: Other: travel; Taiho Oncology, Rigel Pharmaceuticals, Novartis: Consultancy; OncLive, MD Education, Sierra Oncology, Stemline, MorphoSys: Consultancy; Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology, SOBI, Rigel Pharmaceuticals, Geron, Cogent Biosciences and Novartis: Other: Advisory Board; BMS, Kura Oncology, BluePrint Medicines, Geron: Consultancy. Olin: Cellectis: Research Funding; Servier: Consultancy; Rigel: Consultancy. Lin: Aptevo; Bio-Path Holdings; Ciclomed; Cleave; Jazz; Jazz Pharmaceuticals; Leukemia & Lymphoma Society; Kura Oncology; Trovagene: Research Funding; Jazz Pharmaceuticals; Servier: Consultancy. Curran: Jazz Pharmaceuticals: Consultancy; Kite Pharmceuticals: Consultancy; Clincal Care Options: Honoraria; Dava Oncology: Honoraria; Pfizer: Consultancy; Servier: Honoraria. Stefanos: Eilean Therapeutics: Consultancy. Levine: Isoplexis: Membership on an entity's Board of Directors or advisory committees; Scorpion: Membership on an entity's Board of Directors or advisory committees; Mission Bio: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Membership on an entity's Board of Directors or advisory committees; Zentalis: Membership on an entity's Board of Directors or advisory committees; Syndax: Consultancy; Bakx Therapeutics: Membership on an entity's Board of Directors or advisory committees; Prelude Therapeutics: Membership on an entity's Board of Directors or advisory committees; Anovia: Consultancy; Mana: Membership on an entity's Board of Directors or advisory committees; Auron: Membership on an entity's Board of Directors or advisory committees; Ajax: Membership on an entity's Board of Directors or advisory committees; Kurome: Membership on an entity's Board of Directors or advisory committees; Epiphanes: Membership on an entity's Board of Directors or advisory committees; Jubilant: Membership on an entity's Board of Directors or advisory committees; Bridge Bio: Consultancy; Bridge Medicines: Consultancy; Imago: Consultancy; Qiagen: Membership on an entity's Board of Directors or advisory committees. Burd: Eilean Therapeutics: Current Employment. Mims: Novartis: Membership on an entity's Board of Directors or advisory committees; Foghorn Therapeutics: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Daiichi Saynko: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society Beat AML Study: Other: Senior Medical Director; Treadwell Therapeutics: Membership on an entity's Board of Directors or advisory committees. Byrd: Abbvie, AstraZeneca, and Syndax: Consultancy; Vincerx Pharma, Eilean Therapeutics, and Kurome Therapeutics: Current equity holder in private company.
OffLabel Disclosure: The trial investigates an alternative schedule of venetoclax that is not per label.
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