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

Primary Purpose

Non-Hodgkin's Lymphoma, Relapsed, Chronic Lymphoid Leukemia in Relapse, Non-Hodgkin's Lymphoma Refractory

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

PBCAR20A

Fludarabine

Cyclophosphamide

About this trial

This is an interventional treatment trial for Non-Hodgkin's Lymphoma, Relapsed

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

City of Hope
Stanford University
Columbia University
Cleveland Clinic
MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Dose Level 1 of PBCAR20A CAR T cells

Dose Level 2 of PBCAR20A CAR T cells

Dose Level 3 of PBCAR20A CAR T cells

Arm 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.

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

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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

Progression-free Survival (PFS)

Progression-free survival is defined as the duration (days) from Day 0 to disease progression or death.

Full Information

NCT ID

NCT04030195

First Posted

July 19, 2019

Last Updated

January 4, 2023

Sponsor

Precision BioSciences, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04030195

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Completed

Study Start Date

March 24, 2020 (Actual)

Primary Completion Date

June 24, 2021 (Actual)

Study Completion Date

June 24, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Precision BioSciences, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Model Description

Phase 1: Participants with r/r CD20+ B-cell NHL or r/r CLL/SLL will be enrolled to 3 escalating dose groups and treated sequentially, with the possibility of a single de-escalation. Within each dose group, at least 3 and at most 6 study participants will be treated with a single dose of PBCAR20A using a standard 3 + 3 design. The starting dose of PBCAR20A will be 1 × 10^6 chimeric antigen receptor (CAR) T cells/kg body weight. Subsequent dose groups will be treated with escalating doses to a maximum dose of 480 × 10^6 CAR T cells (flat dose). In the absence of dose-limiting toxicities (DLTs) (as described in Section 3.8 of the protocol), the dose will be increased using a fixed-dose scheme. Phase 2: Study PBCAR20A-01 did not proceed into Phase 2.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose Level 1 of PBCAR20A CAR T cells

Arm Type

Experimental

Arm Description

Arm Title

Dose Level 2 of PBCAR20A CAR T cells

Arm Type

Experimental

Arm Description

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

Arm Title

Dose Level 3 of PBCAR20A CAR T cells

Arm Type

Experimental

Arm Description

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

Intervention Type

Genetic

Intervention Name(s)

PBCAR20A

Other Intervention Name(s)

Allogeneic Anti-CD20 CAR T cells

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Fludarabine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximum Tolerated Dose (MTD)

Description

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.

Time Frame

Day 1 to Day 28

Title

Number of Participants With Dose-Limiting Toxicities

Description

Dose-limiting toxicities (DLT) are certain Grade 3 and Grade 4 toxic reactions as defined by the protocol and CTCAE v5.0.

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Objective Response Rate

Description

Time Frame

1 year

Title

Progression-free Survival (PFS)

Description

Progression-free survival is defined as the duration (days) from Day 0 to disease progression or death.

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alan List, MD

Organizational Affiliation

Precision BioSciences, Inc.

Official's Role

Study Chair

Facility Information:

Facility Name

City of Hope

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Name

Stanford University

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

Facility Name

Columbia University

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Cleveland Clinic

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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