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

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ClinicalTrials.gov Identifier: NCT04030195
Recruitment Status : Completed
First Posted : July 23, 2019
Last Update Posted : June 24, 2022
Sponsor:
Information provided by (Responsible Party):
Precision BioSciences, Inc.

Tracking Information
First Submitted Date  ICMJE July 19, 2019
First Posted Date  ICMJE July 23, 2019
Last Update Posted Date June 24, 2022
Actual Study Start Date  ICMJE March 24, 2020
Actual Primary Completion Date June 24, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2019)
  • Maximum Tolerated Dose (MTD) [ Time Frame: Day 1 - Day 28 ]
    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.
  • Number of Participants with Dose Limiting Toxicity(ies) [ Time Frame: 1 year ]
    To assess adverse events as dose limiting toxicities as defined by the protocol and CTCAE v5.0.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2019)
Objective Response Rate of Patients [ Time Frame: 1 year ]
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 22, 2019)
Area Under the Curve [AUC] [ Time Frame: 1 year ]
To evaluate Area Under the Curve [AUC] of PBCAR20A in patients tested.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Dose-escalation Study of Safety of PBCAR20A in Subjects With r/r NHL or r/r CLL/SLL
Official Title  ICMJE 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)
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 (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 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Phase 1: In each cohort, r/r CD20+ B-cell NHL (Cohort A) or r/r CLL/SLL (Cohort B), 3 escalating dose groups will be enrolled 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)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Genetic: PBCAR20A
    Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied.
    Other Name: Allogeneic Anti-CD20 CAR T cells
  • Drug: Fludarabine
    Fludarabine is used for lymphodepletion (30 mg/m^2/day, Days -5 to -3).
  • Drug: Cyclophosphamide
    Cyclophosphamide is used for lymphodepletion (500 mg/m^2/day, Days -5 to -3).
Study Arms  ICMJE
  • Experimental: 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.

    Interventions:
    • Genetic: PBCAR20A
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Dose Level 2 of PBCAR20A CAR T cells
    240 x 10^6 CAR T cells (flat dose)
    Interventions:
    • Genetic: PBCAR20A
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Dose Level 3 of PBCAR20A CAR T cells
    480 x 10^6 CAR T cells (flat dose)
    Interventions:
    • Genetic: PBCAR20A
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 17, 2022)
17
Original Estimated Enrollment  ICMJE
 (submitted: July 22, 2019)
90
Actual Study Completion Date  ICMJE June 24, 2021
Actual Primary Completion Date June 24, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04030195
Other Study ID Numbers  ICMJE PBCAR20A-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Precision BioSciences, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Precision BioSciences, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Alan List, MD Precision BioSciences, Inc.
PRS Account Precision BioSciences, Inc.
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP