Clinical Trials /

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

NCT04030195

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).

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

Interventions

DrugSynonymsArms
FludarabineDose Level 1 of PBCAR20A CAR T cells
CyclophosphamideDose 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

NameTypeDescriptionInterventions
Dose Level 1 of PBCAR20A CAR T cellsExperimental1 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 cellsExperimental3 x 10^6 CAR T cells per kg body weight.
  • Fludarabine
  • Cyclophosphamide
Dose Level 3 of PBCAR20A CAR T cellsExperimental6 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

March 27, 2020