Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dose-escalation Study of Safety of PBCAR0191 in Patients With r/r NHL and r/r B-cell ALL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03666000
Recruitment Status : Recruiting
First Posted : September 11, 2018
Last Update Posted : January 20, 2021
Sponsor:
Information provided by (Responsible Party):
Precision BioSciences, Inc.

Tracking Information
First Submitted Date  ICMJE August 20, 2018
First Posted Date  ICMJE September 11, 2018
Last Update Posted Date January 20, 2021
Actual Study Start Date  ICMJE March 11, 2019
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2018)
  • 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
 (submitted: September 7, 2018)
  • 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.
  • adverse effect [ Time Frame: 1 year ]
    To assess adverse events as either treatment-related or non-treatment-related as defined by CTCAE v5.0.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • 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.
  • Duration of Response [ Time Frame: 1 year ]
    To assess the duration (days) of response from initial response until disease relapse or progression
  • Progression-free Survival [ Time Frame: 1 year ]
    To assess the duration (days) of response from Day 0 to disease progression or death
  • Overall Survival [ Time Frame: 1 year ]
    To assess the duration (days) of response from Day 0 to death
  • Time to next treatment [ Time Frame: 1 year ]
    To assess the duration (days) of response from Day 0 to institution of next therapy
Original Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2018)
  • clinical activity [ 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.
  • Area Under the Curve [AUC] [ Time Frame: Up to 1 year ]
    To evaluate Area Under the Curve [AUC] of PBCAR0191 in patients tested.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dose-escalation Study of Safety of PBCAR0191 in Patients With r/r NHL and r/r B-cell ALL
Official Title  ICMJE Phase 1/2a, Open-label, Dose-escalation/Expansion, Parallel Assignment Study to Evaluate Safety and Clinical Activity of PBCAR0191 in Subjects With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma and r/r B-cell Acute Lymphoblastic Leukemia
Brief Summary This is a Phase 1/2a, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of PBCAR0191 in adults with r/r B ALL (Cohort A) and in adults with r/r B-cell NHL (Cohort N).
Detailed Description This is a multicenter, nonrandomized, open-label, parallel assignment, 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 PBCAR0191 in subjects with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma (NHL). Before initiating PBCAR0191, subjects will be administered lymphodepletion chemotherapy composed of fludarabine and cyclophosphamide. At Day 0 of the Treatment Period, subjects will receive an intravenous (IV) infusion of PBCAR0191. Subjects who receive a split dose will also receive an IV infusion of PBCAR0191 on Day 10 and/or Day 14. Subjects may be considered for retreatment. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of PBCAR0191 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:
In each cohort (NHL and B-ALL), up to 6 dose levels will be enrolled and treated sequentially. Within each dose level, up to 6 subjects will be treated with PBCAR0191 using a standard 3 + 3 design. The starting dose of PBCAR0191 will be 3 × 10^5 CAR T cells/kg body weight. Subsequent dose groups will be treated with escalating doses to a maximum dose of 9 × 10^6 CAR T cells/kg. In the absence of DLTs, the dose will be increased using a fixed dose scheme.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Hodgkin Lymphoma
  • B-cell Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • Genetic: PBCAR0191
    Single dose of Allogeneic Anti-CD19 CAR T cells will be infused
    Other Name: Allogeneic Anti-CD19 CAR T cells
  • Drug: Fludarabine
    Fludarabine is used for lymphodepletion.
  • Drug: Cyclophosphamide
    Cyclophosphamide is used for lymphodepletion.
Study Arms  ICMJE
  • Experimental: Dose Level 1

    PBCAR0191, 3 x 10^5 CAR T cells per kg body weight.

    In this study, PBCAR0191, allogeneic anti-CD19 CAR T Cells, is used to treat patients with relapsed or refractory (r/r) Non-Hodgkin Lymphoma and r/r B-cell Acute Lymphoblastic Leukemia.

    Route of Administration: Intravenous infusion.

    Lymphodepletion Conditioning: Lymphodepletion will be conducted several days prior to PBCAR0191 infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.

    Interventions:
    • Genetic: PBCAR0191
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Dose Level 2
    PBCAR0191, 1 x 10^6 CAR T cells per kg body weight.
    Interventions:
    • Genetic: PBCAR0191
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Dose Level 3a
    PBCAR0191, 3 x 10^6 CAR T cells per kg body weight.
    Interventions:
    • Genetic: PBCAR0191
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Dose Level 3b
    PBCAR0191, 3 x 10^6 CAR T cells per kg body weight as 3 administrations of 1 x 10^6 CAR T cells per kg body weight administered after a single lymphodepletion.
    Interventions:
    • Genetic: PBCAR0191
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Dose Level 4
    PBCAR0191, 6 x 10^6 CAR T cells per kg body weight as 2 administrations of 3 x 10^6 CAR T cells per kg body weight administered after a single lymphodepletion.
    Interventions:
    • Genetic: PBCAR0191
    • Drug: Fludarabine
    • Drug: Cyclophosphamide
  • Experimental: Dose Level 5
    PBCAR0191, 9 x 10^6 CAR T cells per kg body weight as 3 administrations of 3 x 10^6 CAR T cells per kg body weight administered after a single lymphodepletion.
    Interventions:
    • Genetic: PBCAR0191
    • 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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 10, 2020)
92
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2018)
80
Estimated Study Completion Date  ICMJE October 2021
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria*

Criteria for B-ALL:

  • Relapsed or refractory CD19+ B-cell acute lymphoblastic leukemia (B-ALL).
  • Philadelphia chromosome positive (Ph+) disease can be eligible if they are intolerant to tyrosine kinase inhibitor (TKI) therapy or if they have relapsed/refractory disease.

Criteria for NHL:

  • r/r CD19+ B-cell NHL that is histologically confirmed by archived tumor biopsy tissue from last relapse and corresponding pathology report. The following types of lymphoma are included:

    • Diffuse large B-cell lymphoma (DLBCL) including Richter's transformation
    • Primary mediastinal B-cell lymphoma (PMBL)
    • FL including Grade 3B or transformed FL
    • High-grade B-cell lymphoma
    • Small lymphocytic lymphoma (SLL)
    • Mantle cell lymphoma (MCL)
  • Received at least 2 prior chemotherapy-containing regimens. Subjects with SLL must have previously failed at least 2 lines of chemotherapy/immunotherapy that included ibrutinib and idelalisib plus rituximab.
  • Measurable or detectable disease according to the Lugano Classification.
  • Criteria for both B-ALL and NHL:
  • Eastern Cooperative Oncology Group performance status score of 0 or 1.
  • An estimated life expectancy of at least 12 weeks according to the investigator's judgment.
  • Seronegative for human immunodeficiency virus antibody (i.e., intact immune function).
  • Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:

    1. Estimated glomerular filtration rate (eGFR) >50 mL/min/1.73 m2.
    2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both ≤3 times of upper limit of normal, unless there is suspected disease in the liver.
    3. Total bilirubin <2.0 mg/dL, except in subjects with Gilbert's syndrome.
    4. Platelet count ≥30,000/µL (platelet transfusions acceptable).
    5. Left ventricular ejection fraction >45% as assessed by echocardiogram (ECHO) or multiple gated acquisition scan performed within 1 month before starting lymphodepleting chemotherapy. ECHO results performed within 6 months before Screening and at least 28 days after the last cancer treatment may be acceptable if the subject has not received any treatment with cardiotoxicity risks.
    6. No clinically significant evidence of pericardial effusion or pleural effusion.
    7. Baseline oxygen saturation >92% on room air.

Key Exclusion Criteria*

Criteria for B-ALL:

  • Burkitt cell (L3 ALL) or mixed-lineage acute leukemia.
  • Active CNS leukemia.

Criteria for NHL:

  • Active hemolytic anemia.
  • Active CNS lymphoma.
  • Criteria for B-ALL and NHL:
  • Previous malignancy, besides the malignancies of inclusion (B-ALL or NHL), that has a high risk of relapse in the next 2 years.
  • Uncontrolled and serious fungal, bacterial, viral, protozoal, or other infection.
  • Any form of primary immunodeficiency.
  • Active hepatitis B or C.
  • Uncontrolled cardiovascular disease.
  • Hypertension crisis or hypertensive encephalopathy within 3 months.
  • Concomitant genetic syndrome or any other known bone marrow failure syndrome.
  • Active uncontrolled autoimmune disease requiring active immunosuppression (excluding subjects needing steroids for physiologic replacement).
  • Received stem cell transplant within 90 days.
  • Active GvHD symptoms.
  • Received systemic biologic agent within 30 days or 5 half-lives.
  • Received systemic immunostimulatory agent within 30 days or 5 half-lives.
  • Radiotherapy within 4 weeks determined on a case-by-case basis.
  • Presence of pleural/peritoneal/pericardial catheter.
  • Received live vaccine within 4 weeks before Screening.
  • Current use of any anticoagulant or antiplatelet therapy.

    • Additional criteria apply
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: Clinical Precision BioSciences, Inc. 919-314-5512 clinical@precisionbiosciences.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03666000
Other Study ID Numbers  ICMJE PBCAR0191-01
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
Responsible Party Precision BioSciences, Inc.
Study Sponsor  ICMJE Precision BioSciences, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Chris Heery, MD Precision BioSciences, Inc.
PRS Account Precision BioSciences, Inc.
Verification Date July 2020

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