A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of PBCAR0191 in Subjects with Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL)
To evaluate the safety and tolerability of PBCAR0191 in subjects with relapsed/refractory (r/r) Bcell acute lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma (NHL) and find an appropriate dose to optimize safety and efficacy
To evaluate the clinical activity of PBCAR0191 in subjects with r/r B-ALL and NHL
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
Patient has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function
Criteria for B-ALL:
Unequivocal relapsed or refractory CD19+ B-cell acute lymphoblastic leukemia (B-ALL) that has been confirmed by morphology, flow cytometry or a validated MRD assay.
Philadelphia chromosome positive (Ph+) disease can be eligible if they are intolerant to tyrosine kinase inhibitor (TKI) therapy or if they have relapsed/refractory disease
Criteria for NHL:
Unequivocal aggressive CD19+ relapsed/refractory B-cell NHL that is confirmed by archived tumor biopsy tissue from last relapse after CD19 directed therapy and corresponding pathology report
Received at least 2 prior chemotherapy-containing regimens consistent with standard of care treatment guidance (NCCN), unless no second line therapy of known benefit exists for a given patient. Other than those specifically prohibited, other therapies are allowed until 7 days prior to initiation of lymphodepletion (LD). In that case, all screening safety laboratories and disease assessments must be performed after the last dose of prior therapy. For Richter's transformation, only 1 prior line of therapy is required for the DLBCL component.
Has received no more than 7 systemic lines of anti-cancer therapy for the disease under study.
Burkitt cell (L3 B-ALL) or mixed-lineage acute leukemia.
No active CNS disease. Patients with a history of CNS involvement must have a documented CR on at least 2 imaging studies at least 3 months apart (with no masses in parenchyma and no ocular involvement) and a negative CSF cytology on at least 2 evaluations (one evaluation may be during the Screening Period and the other must be at least 3 months prior).
Criteria for NHL:
No prior or active CNS disease.
Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or
blood vessel compression.
Active hemolytic anemia.
Criteria for B-ALL and NHL:
Patient 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, patients may be enrolled with ongoing CLL/SLL.
Uncontrolled and serious fungal, bacterial, viral, protozoal, or other infection that has not resolved and does require therapeutic anti-microbial medications at least 7 days prior to LD. Patients with elevated CRP must undergo infectious disease workup and the recommendations discussed with medical monitor to be considered on an individual basis. The CRP must be trending toward the normal range for the laboratory with the exception when it's deemed related to the underlying malignancy.
Any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease).
Active hepatitis B or hepatitis C confirmed by polymerase chain reaction (PCR). Patient positive for inactive hepatitis B is allowed to enroll if on prophylactic treatment.
Any known uncontrolled cardiovascular disease at the time of Screening that, in the
investigator’s opinion, renders the patient ineligible.
History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening.
History of severe immediate hypersensitivity reaction to any of the agents used in this study.
Presence of a CNS disorder that, in the opinion of the investigator, renders the patient ineligible for treatment.
Abnormal findings during the Screening Period or any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the patient’s safety.
History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.
Active uncontrolled autoimmune disease requiring active immunosuppression at the time of Screening (excluding subjects needing steroids for physiologic replacement).
Patient has received stem cell transplant within 90 days before Screening.
Patient has active GvHD symptoms.
Patient has received systemic biologic agent within 28 days of enrollment. Note: this criterion does not apply if the patient has had clear evidence of disease progression after such an agent has been administered. This should be discussed with the medical monitor for confirmation.
Participation in noninterventional registries or epidemiological studies is not excluded.
Patient has received systemic immunostimulatory agent within 30 days or 5 half-lives before the scheduled PBCAR0191 infusion, whichever is longer. Note: this criterion does not apply if the patient has had clear evidence of disease progression after such an agent has been administered. This should be discussed with the medical monitor for confirmation.
Radiotherapy within 4 weeks before Screening should be discussed with monitor and determined on a case-by-case basis.
Presence of pleural/peritoneal/pericardial catheter.
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