Clinical trial NCT04030195: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Precision BioSciences, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-23
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Day 1 to Day 28
measure: Number of Participants With Dose-Limiting Toxicities
timeFrame: 1 year
Secondary outcomes:
measure: Objective Response Rate
timeFrame: 1 year
measure: Progression-free Survival (PFS)
timeFrame: 1 year
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: New York
country: United States
facility: Columbia University
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Precision BioSciences, Inc.
name: Alan List, MD
role: STUDY_CHAIR
References: