Dose-escalation Study of Safety of PBCAR0191 in Patients With r/r NHL and r/r B-cell ALL
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ClinicalTrials.gov Identifier: NCT03666000 |
Recruitment Status :
Recruiting
First Posted : September 11, 2018
Last Update Posted : January 20, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Non-Hodgkin Lymphoma B-cell Acute Lymphoblastic Leukemia | Genetic: PBCAR0191 Drug: Fludarabine Drug: Cyclophosphamide | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 92 participants |
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 |
Official Title: | 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 |
Actual Study Start Date : | March 11, 2019 |
Estimated Primary Completion Date : | October 2021 |
Estimated Study Completion Date : | October 2021 |

Arm | Intervention/treatment |
---|---|
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. |
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. |
Experimental: Dose Level 2
PBCAR0191, 1 x 10^6 CAR T cells per kg body weight.
|
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. |
Experimental: Dose Level 3a
PBCAR0191, 3 x 10^6 CAR T cells per kg body weight.
|
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. |
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.
|
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. |
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.
|
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. |
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.
|
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. |
- 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.
- 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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:
- Estimated glomerular filtration rate (eGFR) >50 mL/min/1.73 m2.
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels both ≤3 times of upper limit of normal, unless there is suspected disease in the liver.
- Total bilirubin <2.0 mg/dL, except in subjects with Gilbert's syndrome.
- Platelet count ≥30,000/µL (platelet transfusions acceptable).
- 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.
- No clinically significant evidence of pericardial effusion or pleural effusion.
- 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.
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Current use of any anticoagulant or antiplatelet therapy.
- Additional criteria apply

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): NCT03666000
Contact: Clinical Precision BioSciences, Inc. | 919-314-5512 | clinical@precisionbiosciences.com |
United States, California | |
City of Hope | Recruiting |
Duarte, California, United States, 91010 | |
Contact: Clinical Research 626-218-1133 | |
United States, Florida | |
H. Lee Moffitt Cancer Center | Recruiting |
Tampa, Florida, United States, 33612 | |
Contact: Clinical Research 888-663-3488 | |
United States, Georgia | |
Northside Hospital Cancer Institute | Recruiting |
Atlanta, Georgia, United States, 30342 | |
Contact: Scott Solomon, MD 404-255-1930 ssolomon@bmtga.com | |
Principal Investigator: Scott Solomon, MD | |
United States, Indiana | |
Indiana Blood and Marrow | Recruiting |
Indianapolis, Indiana, United States, 46237 | |
Contact: Luke P Akard, MD lakard@ibmtindy.com | |
Principal Investigator: Luke P Akard, MD | |
United States, Massachusetts | |
Dana-Farber Cancer Institute | Recruiting |
Boston, Massachusetts, United States, 02215 | |
Contact: Clinical Trials 877-338-7425 | |
United States, Michigan | |
Barbara Ann Karmanos Cancer Institute (Wayne State University) | Recruiting |
Detroit, Michigan, United States, 48201 | |
Contact: Abhinav Deol, MD 313-576-8093 deola@karmanos.org | |
Principal Investigator: Abhinav Deol, MD | |
United States, Minnesota | |
University of Minnesota | Recruiting |
Minneapolis, Minnesota, United States, 55455 | |
Contact: Fiona He, MD fionahe@umn.edu | |
Principal Investigator: Fiona He, MD | |
United States, New York | |
Weill Cornell Medical College - NY Presbyterian Hospital | Recruiting |
New York, New York, United States, 10021 | |
Contact: Koen Van Besien, MD 646-962-7950 kov9001@med.cornell.edu | |
Principal Investigator: Koen Van Besien, MD | |
Columbia University Irving Medical Center/New York Presbyterian Hospital | Recruiting |
New York, New York, United States, 10032 | |
Contact: Ran Reshef, MD rr3036@cumc.columbia.edu | |
Principal Investigator: Ran Reshef, MD | |
Memorial Sloan Kettering Cancer Center | Recruiting |
New York, New York, United States, 10065 | |
Contact: Craig Sauter, MD | |
United States, Rhode Island | |
Lifespan Cancer Institute at Rhode Island Hospital | Recruiting |
Providence, Rhode Island, United States, 02903 | |
Contact: Adam Olszewski, MD adam_olszewski@brown.edu | |
Principal Investigator: Adam Olszewski, MD | |
United States, Texas | |
MD Anderson | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Clinical Research 855-761-8004 |
Study Chair: | Chris Heery, MD | Precision BioSciences, Inc. |
Responsible Party: | Precision BioSciences, Inc. |
ClinicalTrials.gov Identifier: | NCT03666000 |
Other Study ID Numbers: |
PBCAR0191-01 |
First Posted: | September 11, 2018 Key Record Dates |
Last Update Posted: | January 20, 2021 |
Last Verified: | July 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Lymphoma Leukemia Lymphoma, Non-Hodgkin Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
Cyclophosphamide Fludarabine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists |