PBCAR0191

This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-optimization study to evaluate the safety and clinical activity of PBCAR0191 in adults with r/r B ALL (Cohort A) and in adults with r/r B-cell NHL (Cohort N) and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile.

Inclusion Criteria

1. Criteria for B-ALL: Subject has unequivocal r/r CD19+ B-ALL that has been confirmed by morphology, flow cytometry, or a validated minimal residual disease assay.

2. Criteria for NHL: Subject has unequivocal aggressive CD19+ r/r B-cell NHL that is confirmed by archived tumor biopsy tissue from last relapse after CD19-directed therapy and corresponding pathology report. 

3. Subject has measurable or detectable (for example positron emission tomography-positive) disease according to the Lugano Classification.

Exclusion Criteria

1. Criteria for B-ALL: Burkitt cell (L3 ALL) or mixed-lineage acute leukemia.

2. Criteria for NHL: No prior or active CNS disease.

3. Criteria for B-ALL and NHL: Subject has had a malignancy, besides the malignancies of inclusion (B-ALL or NHL), that in the investigator's opinion, has a high risk of relapse in the next 2 years. In the case of Richter's transformation, subjects may be enrolled with ongoing chronic lymphocytic leukemia/small lymphocytic lymphoma.

Study Requirements

This is a multicenter, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-optimization study to evaluate the safety and tolerability, find an appropriate dose to optimize safety and efficacy, and evaluate clinical activity of PBCAR0191 in subjects with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma (NHL). Before initiating PBCAR0191, subjects will be administered lymphodepletion chemotherapy composed of fludarabine and cyclophosphamide. At Day 0 of the Treatment Period, subjects will receive an intravenous (IV) infusion of PBCAR0191. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of PBCAR0191 will be followed in a separate long-term follow-up (LTFU) study for up to15 years after exiting this study.