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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04030195
• Other study ID #: PBCAR20A-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 24, 2020
• Est. completion date: June 24, 2021

Study information

• Verified date: January 2023
• Source: Precision BioSciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: June 24, 2021
• Est. primary completion date: June 24, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• B-cell Chronic Lymphocytic Leukemia
• B-cell Non Hodgkin Lymphoma
• Chronic Lymphocytic Leukemia
• Chronic Lymphoid Leukemia in Relapse
• Leukemia
• Leukemia, Lymphocytic, Chronic
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma Refractory
• Non-Hodgkin's Lymphoma, Relapsed
• Small Lymphocytic Lymphoma

Intervention

Genetic:
• PBCAR20A
Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied.

Drug:
• Fludarabine
Fludarabine is used for lymphodepletion (30 mg/m^2/day, Days -5 to -3).
• Cyclophosphamide
Cyclophosphamide is used for lymphodepletion (500 mg/m^2/day, Days -5 to -3).

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio
United States	City of Hope	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Columbia University	New York	New York
United States	Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Precision BioSciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Progression-free Survival (PFS)	Progression-free survival is defined as the duration (days) from Day 0 to disease progression or death.	1 year