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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)

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ClinicalTrials.gov Identifier: NCT04030195
Recruitment Status : Not yet recruiting
First Posted : July 23, 2019
Last Update Posted : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
Precision BioSciences, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Genetic: PBCAR20A Drug: Fludarabine Drug: Cyclophosphamide Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : February 2021


Arm Intervention/treatment
Experimental: PBCAR20A-01

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.

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.

Drug: Cyclophosphamide
Cyclophosphamide is used for lymphodepletion.




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. Area Under the Curve [AUC] [ Time Frame: 1 year ]
    To evaluate Area Under the Curve [AUC] of PBCAR20A in patients tested.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04030195


Contacts
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Contact: Clinical Precision BioSciences, Inc. 919-314-5512 clinical@precisionbiosciences.com

Sponsors and Collaborators
Precision BioSciences, Inc.
Investigators
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Study Chair: Chris Heery, MD Chief Medical Officer

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Responsible Party: Precision BioSciences, Inc.
ClinicalTrials.gov Identifier: NCT04030195     History of Changes
Other Study ID Numbers: PBCAR20A-01
First Posted: July 23, 2019    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Rituximab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Immunological