Dose-escalation Study of Safety of PBCAR20A in Subjects With r/r NHL or r/r CLL/SLL

Precision BioSciences

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Genetic: PBCAR20A; Drug: Cyclophosphamide; Drug: Fludarabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT04030195

PBCAR20A-01

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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18 participants in 3 patient groups

Dose Level 1 of PBCAR20A CAR T cells

Experimental group

Description:

1 x 10\^6 chimeric antigen receptor (CAR) T cells per kg body weight. In this study, PBCAR20A, allogeneic anti-cluster of differentiation (CD20) CAR T Cells, is used to treat patients with relapsed or refractory (r/r) CD20+ Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Route of Administration: Intravenous infusion (IV) Lymphodepletion Conditioning: Lymphodepletion will be conducted several days prior to PBCAR20A infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.

Treatment:

Drug: Cyclophosphamide

Drug: Fludarabine

Genetic: PBCAR20A

Dose Level 2 of PBCAR20A CAR T cells

Experimental group

Description:

240 x 10\^6 CAR T cells (flat dose)

Treatment:

Drug: Cyclophosphamide

Drug: Fludarabine

Genetic: PBCAR20A

Dose Level 3 of PBCAR20A CAR T cells

Experimental group

Description:

480 x 10\^6 CAR T cells (flat dose)

Treatment:

Drug: Cyclophosphamide

Drug: Fludarabine

Genetic: PBCAR20A