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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Autologous base edited anti-CD45 CAR T cells
CD45 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.
Time frame: Up to 15 years post infusion
Occurrence of dose-limiting toxicities (DLTs)
Unacceptable toxicity as defined by the protocol. DLTs will be evaluated separately by each disease-specific cohort.
Time frame: 21 days post-CART-45 infusion
Identification of the maximum tolerated dose (MTD)
Selected based on an isotonic regression model. The MTD will be established separately by disease-specific cohort.
Time frame: 21 days post-CART-45 infusion
Identification of a recommended dose for expansion (RDE)
Evaluated by Cohort/dose level using a multi-criteria decision analysis.
Time frame: 3 months post-CART-45 infusion
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.
Time frame: 3 months
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.
Time frame: 3 months
Proportion of CD45BE-HSPC products that fail to meet the protocol-defined dose
Abramson Cancer Center Clinical Trials Service
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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.
Time frame: 3 months
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.
Time frame: 3 months
Evaluate study feasibility
Proportion of eligible patients who receive both investigational products as planned; by individual disease-specific cohort and in aggregate.
Time frame: 3 months
Engraftment of CD45BE-HSPC
Number of subjects with engraftment of CD45BE-HSPC.
Time frame: 28 days after treatment
Overall survival (OS)
Duration of time from CD45BE-HSPC infusion (Day 0) to the date of death, for any reason
Time frame: Up to 15 years after last CART-45 Cells administration
Overall Response/Remission Rate (ORR)
Proportion of subjects with CR or PR at Month 3 as compared to baseline.
Time frame: Month 3
Best Overall Response (BOR)
Proportion of subjects with a best objective disease response of CR or PR recorded between Month 3 and the end of primary follow-up (Month 12); or start of new anticancer therapy, whichever comes first.
Time frame: From Month 3 up to Month 12
Duration of Response (DOR)
Time from the date when the response criteria of CR or PR is first met (at or following Month 3), to the date of confirmed disease progression, death, or other censoring event as described below.
Time frame: From Month 3 up to 15 years
Progression-Free Survival (PFS)
The duration of time from the CD45BE-HSPC transplant (Day 0) to the date of confirmed disease progression or death, whichever occurs first. Otherwise, PFS will be censored at the date of the last response assessment, date of new anti-cancer treatment is initiated (including CART-45 retreatment) or the data cut-off date; whichever occurs first.
Time frame: Up to 15 years