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

Phase 1

Completed

• 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
• Interventions: Genetic: PBCAR20A; Drug: Fludarabine; Drug: Cyclophosphamide

• Registration Number: NCT04030195
• Lead Sponsor: Precision BioSciences, Inc.

Brief 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.

Detailed 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.

Study Timeline

• Study First Submitted: 2019-07-19
• Study First Submitted QC: 2019-07-22
• Study First Posted: 2019-07-23
• Study Start: 2020-03-24
• Primary Completion: 2021-06-24
• Study Completion: 2021-06-24
• Results First Submitted: 2022-11-21
• Status Verified: 2023-01
• Results First Submitted QC: 2023-01-04
• Last Update Submitted: 2023-01-04
• Results First Posted: 2023-01-31
• Last Update Posted: 2023-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

Not provided

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Level 2 of PBCAR20A CAR T cells	PBCAR20A	240 x 10\^6 CAR T cells (flat dose)
Dose Level 1 of PBCAR20A CAR T cells	PBCAR20A	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.
Dose Level 3 of PBCAR20A CAR T cells	PBCAR20A	480 x 10\^6 CAR T cells (flat dose)
Dose Level 2 of PBCAR20A CAR T cells	Fludarabine	240 x 10\^6 CAR T cells (flat dose)
Dose Level 1 of PBCAR20A CAR T cells	Cyclophosphamide	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.
Dose Level 1 of PBCAR20A CAR T cells	Fludarabine	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.
Dose Level 2 of PBCAR20A CAR T cells	Cyclophosphamide	240 x 10\^6 CAR T cells (flat dose)
Dose Level 3 of PBCAR20A CAR T cells	Fludarabine	480 x 10\^6 CAR T cells (flat dose)
Dose Level 3 of PBCAR20A CAR T cells	Cyclophosphamide	480 x 10\^6 CAR T cells (flat dose)

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD)	Day 1 to Day 28	The maximum tolerated dose (MTD) is the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy.
Number of Participants With Dose-Limiting Toxicities	1 year	Dose-limiting toxicities (DLT) are certain Grade 3 and Grade 4 toxic reactions as defined by the protocol and CTCAE v5.0.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate	1 year	Objective response rate (ORR) is a measure of clinical activity as response in NHL by the revised Lugano Classification (Cheson et al, 2016) or a response in CLL/SLL by the International Workshop on Chronic Lymphocytic Leukemia 2018 guidelines.
Progression-free Survival (PFS)	1 year	Progression-free survival is defined as the duration (days) from Day 0 to disease progression or death.

Trial Locations

Locations (5)

City of Hope; 🇺🇸 Duarte, California, United States

Stanford University; 🇺🇸 Stanford, California, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Columbia University; 🇺🇸 New York, New York, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States