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

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-03-24

Study Completion Date

2021-06-24

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

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.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

PBCAR20A

Intervention Type GENETIC

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

Fludarabine

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

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

Dose Level 2 of PBCAR20A CAR T cells

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

Group Type EXPERIMENTAL

PBCAR20A

Intervention Type GENETIC

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

Fludarabine

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

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

Dose Level 3 of PBCAR20A CAR T cells

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

Group Type EXPERIMENTAL

PBCAR20A

Intervention Type GENETIC

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

Fludarabine

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

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

Interventions

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PBCAR20A

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

Intervention Type GENETIC

Fludarabine

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

Intervention Type DRUG

Cyclophosphamide

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

Intervention Type DRUG

Other Intervention Names

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Allogeneic Anti-CD20 CAR T cells

Eligibility Criteria

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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.

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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No