NCT04030195

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Mar 2020

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 19, 2019

Completed
4 days until next milestone

First Posted

Study publicly available on registry

July 23, 2019

Completed
8 months until next milestone

Study Start

First participant enrolled

March 24, 2020

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 24, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 24, 2021

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

January 31, 2023

Completed
Last Updated

January 31, 2023

Status Verified

January 1, 2023

Enrollment Period

1.3 years

First QC Date

July 19, 2019

Results QC Date

November 21, 2022

Last Update Submit

January 4, 2023

Conditions

Non-Hodgkin's Lymphoma, RelapsedChronic Lymphoid Leukemia in RelapseNon-Hodgkin's Lymphoma RefractoryChronic Lymphocytic LeukemiaLymphoma, Non-HodgkinLeukemia, Lymphocytic, ChronicB-cell Chronic Lymphocytic LeukemiaB-cell Non Hodgkin LymphomaSmall Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

  • Maximum Tolerated Dose (MTD)

    The maximum tolerated dose (MTD) is the dose level at which fewer than 33% of patients experience a dose limiting toxicity (DLT) using a 3+3 strategy.

    Day 1 to Day 28

  • Number of Participants With Dose-Limiting Toxicities

    Dose-limiting toxicities (DLT) are certain Grade 3 and Grade 4 toxic reactions as defined by the protocol and CTCAE v5.0.

    1 year

Secondary Outcomes (2)

  • Objective Response Rate

    1 year

  • Progression-free Survival (PFS)

    1 year

Study Arms (3)

Dose Level 1 of PBCAR20A CAR T cells

EXPERIMENTAL

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.

Genetic: PBCAR20ADrug: FludarabineDrug: Cyclophosphamide

Dose Level 2 of PBCAR20A CAR T cells

EXPERIMENTAL

240 x 10\^6 CAR T cells (flat dose)

Genetic: PBCAR20ADrug: FludarabineDrug: Cyclophosphamide

Dose Level 3 of PBCAR20A CAR T cells

EXPERIMENTAL

480 x 10\^6 CAR T cells (flat dose)

Genetic: PBCAR20ADrug: FludarabineDrug: Cyclophosphamide

Interventions

PBCAR20AGENETIC

Single dose of Allogeneic Anti-CD20 CAR T cells will be infused, and a classic "3+3" dose escalation will be applied.

Also known as: Allogeneic Anti-CD20 CAR T cells
Dose Level 1 of PBCAR20A CAR T cellsDose Level 2 of PBCAR20A CAR T cellsDose Level 3 of PBCAR20A CAR T cells
FludarabineDRUG

Fludarabine is used for lymphodepletion (30 mg/m\^2/day, Days -5 to -3).

Dose Level 1 of PBCAR20A CAR T cellsDose Level 2 of PBCAR20A CAR T cellsDose Level 3 of PBCAR20A CAR T cells
CyclophosphamideDRUG

Cyclophosphamide is used for lymphodepletion (500 mg/m\^2/day, Days -5 to -3).

Dose Level 1 of PBCAR20A CAR T cellsDose Level 2 of PBCAR20A CAR T cellsDose Level 3 of PBCAR20A CAR T cells

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • 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.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

City of Hope

Duarte, California, 91010, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-HodgkinRecurrenceLeukemia, Lymphocytic, Chronic, B-CellLymphoma, B-Cell

Interventions

fludarabineCyclophosphamide

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesChronic Disease

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Results Point of Contact

Title
Michael Karg, Senior Director, Clinical Operations
Organization
Precision BioSciences
michael.karg@precisionbiosciences.com
919-324-5512

Study Officials

  • Alan List, MD

    Precision BioSciences, Inc.

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 19, 2019

First Posted

July 23, 2019

Study Start

March 24, 2020

Primary Completion

June 24, 2021

Study Completion

June 24, 2021

Last Updated

January 31, 2023

Results First Posted

January 31, 2023

Record last verified: 2023-01

Data Sharing

IPD Sharing
Will not share

Locations

US(5)