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.
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. 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.
✓. Brentuximab vedotin and immune checkpoint inhibitors (unless contraindicated); AND
✓. Autologous stem cell transplant (unless patient has chemorefractory disease to salvage treatment) d. Large Cell Transformation of CLL (Richter's Transformation) i. Patients must be primary refractory or received at least 1 prior line of treatment for Richter's Transformation.
✓. Serum creatinine ≤ 1.5x ULN or estimated creatinine clearance ≥ 35 mL/min and not on dialysis
✓. ALT/AST ≤ 3 x ULN
Exclusion criteria
✕. Active hepatitis B or hepatitis C infection
✕. Any active, uncontrolled infection.
✕. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
What they're measuring
1
Incidence of Adverse Events as assessed by CTCAE v6.0
Timeframe: Up to 15 years post infusion
2
Occurrence of dose-limiting toxicities (DLTs)
Timeframe: 28 days post-CART-45 infusion
3
Identification of the maximum tolerated dose (MTD)
Timeframe: 28 days post-CART-45 infusion
4
Identification of a recommended dose for expansion (RDE)
✕. Clinically apparent arrhythmia or arrhythmias that are not stable on medical management within two weeks of physician-investigator confirmation of eligibility.
✕. Severe, active co-morbidity that, in the opinion of the physician-investigator, would preclude participation in this study.
✕. Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
✕. Active acute or chronic GVHD requiring systemic therapy.
✕. Dependence on systemic steroids or immunosuppressant medications. For additional details regarding use of steroid and immunosuppressant medications.