Streamlined Operational Approaches and Use of e-Technologies in Clinical Trials: Beat Acute Myeloid Leukemia Master Trial

Abstract

Advances in genomic technologies and an increased understanding of the molecular pathogenesis of cancer have resulted in development of new effective, mutation-targeted therapies. In turn, these informed the development of Master Trial designs to test these therapies. The Beat Acute Myeloid Leukemia (BAML) Master Trial (Sponsor: The Leukemia & Lymphoma Society) tests several targeted therapies in patients aged ≥ 60 years with AML based on genomic profiling obtained within 7 days of study enrollment. We hypothesized that integrating operational strategies with new electronic technologies (e-technologies) might streamline the conduct and management of this Master Trial. BAML's 5 core operational strategies revolve around the guiding principle of "patients first." The e-technology platforms employed in BAML include: Clinical Oversight Platform: a central collaborative tool; e-Protocol/e-Source Upload/Electronic Data Capture Platform: digitizes the protocol, allows remote data monitoring, and collects/exports data in Study Data Tabulation Model format; and Data Review Platform: ingests data from different sources for clinical response and safety data reviews. The operational approaches, e-technologies and sponsor/contract research organization's (CRO) expertise together allow: the complexity and size of the BAML Master Trial to be better managed; near real-time study data oversight; better collaboration, communication and training; improved data collection, enhanced transmission and accessibility; data integration, review and generation of reports; while maintaining data privacy, and compliance. Initial e-technology challenges were overcome through training, learning, discipline and adjustment. In conclusion, to successfully manage Master Trials, significant time should be spent re-evaluating, improving and developing new operational approaches.Clinical Trial Registration: Clinical Trials.gov Identifier: NCT03013998. https://ichgcp.net/clinical-trials-registry/NCT03013998 .

Keywords: Artificial intelligence; Clinical trials; E-technologies; EDC; EHR-to-EDC; Remote monitoring.

Conflict of interest statement

Hugh Levaux, and Amit Shat, are employees of Protocol First. James Denmark is an employee of myClin. Ross L. Levine is on the Supervisory board of Qiagen, is on the SAB of Loxo (until 2019), Imago, Mission Bio, Mana, Auron, C4 Therapeutics and Isoplexis which include equity interest. He receives research support from and consulted for Celgene and Roche and consults for Incyte, Lilly, Janssen, Astellas, Morphosys and Novartis. He receives research support from Prelude. He has received honoraria from Astra Zeneca, Roche, Lilly and Amgen for invited lectures and from Gilead Sciences, Inc. for grant reviews. Melanie Owen, Spencer Kalk, Nicholas Kenny and Gene Vinson are employees of Syneos Healthcare. Alice Mims consulting (Ad Boards) for Jazz Pharmaceuticals, Abbvie/Genentech, Astellas, PTC Therapeutics, Novartis, Agios, and Syndax Therapeutics. Uma Borate consulting for Genetech, Daiichi Sankyo, Takeda, Pfizer, AbbVie/Genentech, and Novartis. William Blum reports commercial research support from Forma, Xencor, Celyad, and honoraria from AmerisourceBergen. Eytan Stein: Served on advisory boards for: Astellas, AbbVie, Genentech, Daiichi, Novartis, Amgen, Seattle Genetics, Syros, Syndax, Agios, Celgene. Equity Holder in Auron Therapeutics. Theophilus J. Gana is a Clinical Consultant to Leukemia & Lymphoma Society. Equity stake in Bausch Health. Brian J.Drucker: potential competing interests – SAB: Aileron Therapeutics, Therapy Architects (ALLCRON), Cepheid, Vivid Biosciences, Celgene, RUNX1 Research Program, EnLiven Therapeutics, Gilead Sciences (inactive), Monojul (inactive); SAB & Stock: Aptose Biosciences, Blueprint Medicines, Iterion Therapeutics, Third Coast Therapeutics, GRAIL (SAB inactive); Scientific Founder: MolecularMD (inactive, acquired by ICON); Board of Directors & Stock: Amgen; Board of Directors: Burroughs Wellcome Fund, CureOne; Joint Steering Committee: Beat AML LLS; Founder: VB Therapeutics; Clinical Trial Funding: Novartis, Bristol-Myers Squibb, Pfizer; Royalties from Patent 6958335 (Novartis exclusive license) and OHSU and Dana-Farber Cancer Institute (one Merck exclusive license). John Byrd—Research support from: Janssen; Genentech; Acerta; Pharmacyclics; Advisory Board: Syndax; National Cancer Institute (R35 CA197734, JCB) and in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. Len Rosenberg, Ashley Yocum, Sonja Marcus, and Amy Burd are employees of LLS. LLS receives funding from: AbbVie, Agios Pharmaceuticals, Inc., Alexion Pharmaceuticals, Amgen, Astellas, Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Boston Biomedical, Inc., Bristol-Myers Squibb, Celgene Corporation, Genentech, Gilead Sciences, Inc., ImmunoGen, Jazz, Johnson & Johnson, Novartis, Pfizer, Pharmacyclics, RTI Health, Shire, and Takeda Pharmaceutical Company Ltd. Nyla Hereema, Jo-Anne Vergilio, Mona Stefanos, and Abigail Shoben have nothing to disclose.

© 2021. The Author(s).

Figures

Figure 1

Schematic of Beat AML flow of information, and of patients into the Sub-Studies, and the flow of pharmacokinetic samples. Following screening (cytogenetics and next-generation sequencing) and central treatment decision, patients were enrolled into the 13 sub-studies where they were treated with one of the 9 investigational targeted therapies as monotherapy and/or combination therapy with either azacitidine or decitabine