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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://clinicaltrials.gov/ct2/show/NCT03013998.

Background: The dose response of postprandial plasma glucose (PPG) to add-on, premeal oral hepatic-directed vesicle-insulin (HDV-I), an investigational lipid bio-nanoparticle hepatocyte-targeted insulin delivery system, was evaluated in a 3-test-meal/day model in type 2 diabetes patients. Method: The single-blind, placebo-controlled, dose-escalating trial enrolled 6 patients with HbA1c 8.6 ± 2.0% (70.0 ± 21.9 mmol/mol) and on stable metformin therapy. Patients received oral HDV-I capsules daily 30 minutes before breakfast, lunch, and dinner as follows: placebo capsules, 0.05, 0.1, 0.2, and 0.4 U/kg on days 1, 2, 3, 4, and 5, respectively. Outcome measures were PPG and incremental PPG area under the concentration-time curve (AUC). Results: All 4 doses of oral HDV-I statistically significantly lowered mean PPG ( P ≤ .0110 each) and incremental PPG ( P ≤ .0352 each) AUC compared to placebo. A linear dose response was not observed. The 0.05 U/kg dose was the minimum effective dose in the dosage range studied. Three adverse events unrelated to treatment were observed. Conclusions: Add-on oral HDV-I 0.05-0.4 U/kg significantly lowered PPG excursions and the dose response curve was flat. These results are consistent with the lack of a linear dose response between portal and systemic plasma insulin concentrations in previous animal and human studies. Oral HDV-I was safe and well tolerated.