dose-escalation study of safety of pbcar20a in subjects with r/r nhl or r/r cll/sll

Conditions: Non-Hodgkin's Lymphoma, Relapsed; Chronic Lymphoid Leukemia in Relapse; Non-Hodgkin's Lymphoma Refractory; Chronic Lymphocytic Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic; B-cell Chronic Lymphocytic Leukemia; B-cell Non Hodgkin Lymphoma; Small Lymphocytic Lymphoma

Summary: this is a phase 1/2a, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of pbcar20a in adult subjects with r/r b-cell nhl or r/r cll/sll.

this is a multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study to evaluate safety, tolerability, clinical activity, and find an appropriate dose to optimize safety and efficacy of pbcar20a in subjects with relapsed/refractory (r/r) cd20+ non-hodgkin lymphoma (nhl) or r/r chronic lymphocytic leukemia (cll) or small lymphocytic lymphoma (sll). before initiating pbcar20a, therapy, subjects will be administered lymphodepletion chemotherapy composed of fludarabine and cyclophosphamide. at day 0 of the treatment period, subjects will receive a single intravenous (iv) infusion of pbcar20a. all subjects are monitored during the treatment period through day 28. all subjects who receive a dose of pbcar20a will be followed in a separate long-term follow-up (ltfu) study for 15 years after exiting this study.

Eligibility criteria:
key inclusion criteria criteria for nhl: * r/r cd20+ b-cell nhl that is histologically confirmed by archived tumor biopsy tissue from the last relapse and corresponding pathology report. * measurable or detectable disease according to the lugano classification. * primary refractory disease or r/r disease after a response to 2 prior regimens. criteria for cll/sll: * diagnosis of cd20+ cll with indication for treatment based on the iwcll guidelines and clinically measurable disease or sll with measurable disease that is biopsy-proven sll. * previously failed/tolerant to at least 2 prior lines of systemic targeted therapy of known benefit. criteria for both nhl and cll/sll: * study participant has an eastern cooperative oncology group (ecog) performance status score of 0 or 1. * study participant has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function. key exclusion criteria: criteria for nhl: * requirement for urgent therapy due to mass effects such as bowel obstruction, spinal cord, or blood vessel compression. * active central nervous system (cns) disease. a negative computed tomography (ct)/magnetic resonance imaging (mri) is required at screening if the study participant has a history of cns lymphoma. criteria for nhl and cll/sll: * active cns disease. a negative lumbar puncture is required at screening if the study participant has a history of cns disease. * previous malignancy, besides the malignancies of inclusion (b-cell nhl or cll/sll), that in the investigator's opinion, has a high risk of relapse in the next 2 years. * active uncontrolled fungal, bacterial, viral, protozoal, or other infection. * any form of primary immunodeficiency. * history of human immunodeficiency virus (hiv) infection. * active hepatitis b or c. * uncontrolled cardiovascular disease. * hypertension crisis or hypertensive encephalopathy within 3 months prior to screening. * presence of a cns disorder that renders ineligible for treatment. * history of a genetic syndrome such as fanconi anemia, kostmann syndrome, shwachman diamond syndrome, or any other known bone marrow failure syndrome. * received asct within 45 days of screening if the study participant has met the rest of the count requirements. * must not have received systemic corticosteroid therapy for at least 7 days prior to initiating lymphodepletion chemotherapy. * received a live vaccine within 4 weeks before screening. * radiotherapy within 4 weeks determined on a case-by-case basis. * presence of a pleural/peritoneal/pericardial catheter. * current use of any anticoagulant or antiplatelet therapy.