Materials and Methods
toxicity, AML, DLTs, allogeneic hematopoietic stem cell transplant
DISEASE, AML
The study was designed as an open-label, safety and efficacy, escalating dose, single arm study on 9 adult patients (3 cohorts) and 3 + 3 design was to be used. Human leukocyte antigens (HLA) typed patients and potential blood-related donors were screened for comorbidities. Suitably matched or haploidentical family donors were selected according to protocol specified criteria and institutional guidelines of participating site. There was no formal sample size calculation for the study; a standard 3 + 3 dose escalation design was to be employed.Adult patients with relapsed or refractory AML with greater than 5% of blasts in bone marrow or peripheral blood with a life expectancy of at least 3 months and Karnofsky performance score >50% were included in the study. Patients needed to be unsuitable for high dose salvage chemotherapy and/or allogeneic hematopoietic stem cell transplant and have a related HLA-haploidentical or HLA-matched donor. Full eligibility and exclusion criteria of patient and donor are shown in Supplemental Tables 1A and B.Mononuclear cells were collected by apheresis from healthy donors. The apheresis starting material was then shipped to TC BioPharm (TCB) to undergo processing, with all remaining aspects of the manufacturing process carried out internally at TCB's Manufacturing Facility. Peripheral blood mononuclear cells (PBMCs) were isolated from the apheresis starting material via density gradient centrifugation, using semiautomated devices to minimize open vessel manipulations and variability. The PBMCs were then resuspended in cryoprotectant and aliquoted into vials at the required concentrations to create intermediate cell aliquots (ICAs). ICAs were submitted to the quality control department for controlled rate freezing and storage in vapor phase liquid nitrogen (vLNPatients were administered lymphodepleting chemotherapy with fludarabine 25 mg/mThe schedule of investigation assessed disease burden and response, detected infused products, and monitored toxicity (TCB-202-001 Trial schematic. D denotes day. Donor and patient screening commenced between day –42 and –18. Apheresis of donor material was completed by day –18. OmnImmune (the Investigational Medicinal Product - IMP) manufactured within 14 days. Patients received conditioning chemotherapy from day –6 to –2. IMP dosing on day 0. Follow-up from day 1 through 2 years. SRC denotes safety review committee. SRC assessed safety and efficacy on day 14 and day 28. The trial was conducted in accordance with the ethical principles of the Declaration of Helsinki and the International Council of Harmonization Guidelines on Good Clinical Practice. All patients provided written informed consent.The statistical analysis was descriptive in nature. The incidence of DLTs was summarized descriptively by γδ T cells dose for evaluable subjects. In this case, evaluable patients consisted of all patients completing the period of evaluation for DLTs or who experienced a DLT before completing that period. Safety data from each cohort were reviewed by the safety review committee (SRC) after the completion of the DLT evaluation period for each cohort. Since no statistical testing was performed, no adjustment for interim analysis was required. All other data will be summarized descriptively by γδ T cells dose for all treated patients.