This is a phase 1, open-label, dose-finding study to assess the safety, feasibility, pharmacokinetics and preliminary efficacy of autologous base edited anti-CD45 CAR T cells (referred to as "CART-45 cells") following an autologous transplant of CD45 base edited hematopoietic stem and progenitor cells (referred to as "CD45BE-HSPC") in patients with relapsed or refractory hematologic malignancies.
Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
Relapsed/refractory disease after at least 2 prior lines of systemic therapy (not including a single agent monoclonal antibody therapy).
Patients must have either failed/relapsed after, or be ineligible for, prior commercial CAR T cell therapy; AND
Relapsed/refractory disease after at least 2 prior lines of systemic therapy, including a Bruton tyrosine kinase (TKI) inhibitor. Single-agent monoclonal antibody therapy does not count towards prior lines of therapy.
Active hepatitis B or hepatitis C infection
Any active, uncontrolled infection.
Class III/IV cardiovascular disability according to the New York Heart Association Classification.
Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
Parallel
CART-45 cells
Biological/VaccineAutologous base edited anti-CD45 CAR T cells
CD45BE-HSPC
Biological/VaccineCD45 base edited hematopoietic stem and progenitor cells
Incidence of Adverse Events as assessed by CTCAE v6.0
Type, frequency and severity of adverse events as assessed by CTCAE V6.0. Each disease-specific cohort will be analyzed separately.
Occurrence of dose-limiting toxicities (DLTs)
Unacceptable toxicity as defined by the protocol. DLTs will be evaluated separately by each disease-specific cohort.
Identification of the maximum tolerated dose (MTD)
Selected based on an isotonic regression model. The MTD will be established separately by disease-specific cohort
Identification of a recommended dose for expansion (RDE)
Evaluated by Cohort/dose level using a multi-criteria decision analysis.
Proportion of CD45BE-HSPC products that fail to meet the product release criteria
Calculated based on the proportion of subjects with CD45BE-HSPC products that fail to meet the product release criteria, out of the number of subjects in whom manufacturing was attempted.
Proportion of CART-45 products that fail to meet the product release criteria
Calculated based on the proportion of subjects with CART-45 products that fail to meet the product release criteria, out of the number of subjects in whom manufacturing was attempted.
Proportion of CD45BE-HSPC products that fail to meet the protocol-defined dose
Calculated based on the proportion of subjects with CD45BE-HSPC products that fail to meet the assigned dose, out of the number of subjects in whom manufacturing was attempted.
Proportion of CART-45 products that fail to meet the assigned dose.
Calculated based on the proportion of subjects with CART-45 products that fail to meet the assigned dose, out of the number of subjects in whom manufacturing was attempted.
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University of Pennsylvania
Lead sponsor
Kite, A Gilead Company
Collaborator
