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

A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of PBCAR20A in Subjects With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma, Non-Hodgkin; Chronic Lymphocytic Leukemia; B-cell Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; B-cell Non Hodgkin Lymphoma; Leukemia, Lymphocytic, Chronic; Non-Hodgkin's Lymphoma, Relapsed; Non-Hodgkin's Lymphoma Refractory; Chronic Lymphoid Leukemia in Relapse
• Intervention / Treatment: Genetic: PBCAR20A; Drug: Fludarabine; Drug: Cyclophosphamide

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City Of Hope
    • Stanford, California, United States, 94305
      • Stanford University
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dose Level 1 of PBCAR20A CAR T cells; 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.	Genetic: PBCAR20A; Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied.; Other Names: Allogeneic Anti-CD20 CAR T cells; Drug: Fludarabine; Fludarabine is used for lymphodepletion (30 mg/m^2/day, Days -5 to -3).; Drug: Cyclophosphamide; Cyclophosphamide is used for lymphodepletion (500 mg/m^2/day, Days -5 to -3).
EXPERIMENTAL: Dose Level 2 of PBCAR20A CAR T cells; 240 x 10^6 CAR T cells (flat dose)	Genetic: PBCAR20A; Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied.; Other Names: Allogeneic Anti-CD20 CAR T cells; Drug: Fludarabine; Fludarabine is used for lymphodepletion (30 mg/m^2/day, Days -5 to -3).; Drug: Cyclophosphamide; Cyclophosphamide is used for lymphodepletion (500 mg/m^2/day, Days -5 to -3).
EXPERIMENTAL: Dose Level 3 of PBCAR20A CAR T cells; 480 x 10^6 CAR T cells (flat dose)	Genetic: PBCAR20A; Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied.; Other Names: Allogeneic Anti-CD20 CAR T cells; Drug: Fludarabine; Fludarabine is used for lymphodepletion (30 mg/m^2/day, Days -5 to -3).; Drug: Cyclophosphamide; Cyclophosphamide is used for lymphodepletion (500 mg/m^2/day, Days -5 to -3).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Tolerated Dose (MTD)	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.	Day 1 to Day 28
Number of Participants With Dose-Limiting Toxicities	Dose-limiting toxicities (DLT) are certain Grade 3 and Grade 4 toxic reactions as defined by the protocol and CTCAE v5.0.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	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.	1 year
Progression-free Survival (PFS)	Progression-free survival is defined as the duration (days) from Day 0 to disease progression or death.	1 year

Collaborators and Investigators

• Sponsor: Precision BioSciences, Inc.
• Investigators: Study Chair: Alan List, MD, Precision BioSciences, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 24, 2020
• Primary Completion (ACTUAL): June 24, 2021
• Study Completion (ACTUAL): June 24, 2021

Study Registration Dates

• First Submitted: July 19, 2019
• First Submitted That Met QC Criteria: July 22, 2019
• First Posted (ACTUAL): July 23, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2023
• Last Update Submitted That Met QC Criteria: January 4, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Lymphoma; Lymphoma, B-Cell; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: PBCAR20A-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No