Description:
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 study participants with r/r B-cell NHL (Cohort A) or r/r CLL/SLL (Cohort
B).
Title
- 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 Study Participants With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL)
Clinical Trial IDs
- ORG STUDY ID:
PBCAR20A-01
- NCT ID:
NCT04030195
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
Interventions
Drug | Synonyms | Arms |
---|
Fludarabine | | Dose Level 1 of PBCAR20A CAR T cells |
Cyclophosphamide | | Dose Level 1 of PBCAR20A CAR T cells |
Purpose
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 study participants with r/r B-cell NHL (Cohort A) or r/r CLL/SLL (Cohort
B).
Detailed Description
This is a multicenter, nonrandomized, open-label, parallel assignment, single-dose,
dose-escalation, and dose-expansion study to evaluate the safety and tolerability, find an
appropriate dose to optimize safety and efficacy, and evaluate 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). Before initiating PBCAR20A,
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose Level 1 of PBCAR20A CAR T cells | Experimental | 1 x 10^6 CAR T cells per kg body weight.
In this study, PBCAR20A, allogeneic anti-CD20 CAR T Cells, is used to treat patients with relapsed or refractory (r/r) Non-Hodgkin Lymphoma (NHL) or r/r Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).
Route of Administration: Intravenous infusion.
Lymphodepletion Conditioning: Lymphodepletion will be conducted several days prior to PBCAR20A infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion. | - Fludarabine
- Cyclophosphamide
|
Dose Level 2 of PBCAR20A CAR T cells | Experimental | 3 x 10^6 CAR T cells per kg body weight. | - Fludarabine
- Cyclophosphamide
|
Dose Level 3 of PBCAR20A CAR T cells | Experimental | 6 x 10^6 CAR T cells per kg body weight. | - Fludarabine
- Cyclophosphamide
|
Eligibility Criteria
Key Inclusion Criteria*
Criteria for NHL:
- r/r 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 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 CLL/SLL:
- Active CNS disease. A negative lumbar puncture is required at Screening if the study
participant has a history of CNS disease.
Criteria for NHL and CLL/SLL:
- 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.
- Active hemolytic anemia.
- 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 1 day prior to
initiating lymphodepletion chemotherapy.
- Received a systemic biologic agent within 30 days or 5 half-lives.
- Received a live vaccine within 4 weeks before Screening.
- Received standard cytotoxic chemotherapy within 10 days of 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.
- Additional criteria apply
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum Tolerated Dose (MTD) |
Time Frame: | Day 1 - Day 28 |
Safety Issue: | |
Description: | To determine the maximum tolerated dose (MTD), which is defined as the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy. |
Secondary Outcome Measures
Measure: | Objective Response Rate of Patients |
Time Frame: | 1 year |
Safety Issue: | |
Description: | To assess clinical activity as response in B-ALL by the NCCN Guidelines on ALL (NCCN, 2017) and in NHL by the revised Lugano Classification (Cheson et al, 2016), both reported as objective response rate. |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Precision BioSciences, Inc. |
Last Updated
April 29, 2021