Dose-finding based on feasibility and toxicity in T-cell infusion trials

Area of Science:

• Immunotherapy
• Oncology
• Clinical Trial Design

Background:

• Cancer treatment increasingly uses ex vivo expanded T-cells for targeted cell destruction.
• Determining the maximal tolerated dose (MTD) is crucial for phase II clinical trials but faces challenges in T-cell infusion therapies.
• Traditional dose-finding methods are insufficient due to potential ex vivo cell count limitations.

Purpose of the Study:

• To propose a novel algorithm for determining a feasible MTD in T-cell infusion cancer trials.
• To address the limitations of existing dose-finding strategies by incorporating cell infusibility and toxicity.
• To provide a safe and reliable method for MTD determination in immunotherapy trials.

Main Methods:

• Developed an adaptive algorithm to determine MTD based on dose-dependent probabilities of infusibility and toxicity.
• Applied the proposed method to a dendritic cell-activated lymphocyte infusion trial for acute leukemia.
• Utilized simulation studies to evaluate the safety and reliability of the new algorithm.

Main Results:

• The proposed algorithm successfully determines a feasible MTD by considering both cell availability and patient safety.
• Simulation results demonstrated the safety and reliability of the novel dose-finding methodology.
• The method is applicable to T-cell infusion trials, enhancing early-phase clinical development.

Conclusions:

• The developed algorithm offers a robust solution for MTD determination in T-cell immunotherapy.
• This approach enhances the feasibility and safety of early-phase clinical trials for adoptive cell therapies.
• The methodology provides a reliable framework for advancing T-cell based cancer treatments.