Description:
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).
Title
- Brief Title: Dose-escalation Study of Safety of PBCAR0191 in Patients With r/r NHL and r/r B-cell ALL
- 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
Clinical Trial IDs
- ORG STUDY ID:
PBCAR0191-01
- NCT ID:
NCT03666000
Conditions
- Non-Hodgkin Lymphoma
- B-cell Acute Lymphoblastic Leukemia
Interventions
Drug | Synonyms | Arms |
---|
Fludarabine | | Dose Level 1 |
Cyclophosphamide | | Dose Level 1 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Dose Level 1 | Experimental | 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. | - Fludarabine
- Cyclophosphamide
|
Dose Level 2 | Experimental | PBCAR0191, 1 x 10^6 CAR T cells per kg body weight. | - Fludarabine
- Cyclophosphamide
|
Dose Level 3a | Experimental | PBCAR0191, 3 x 10^6 CAR T cells per kg body weight. | - Fludarabine
- Cyclophosphamide
|
Dose Level 3b | Experimental | 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. | - Fludarabine
- Cyclophosphamide
|
Dose Level 4 | Experimental | 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. | - Fludarabine
- Cyclophosphamide
|
Dose Level 5 | Experimental | 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. | - Fludarabine
- Cyclophosphamide
|
Eligibility Criteria
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
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. |
Measure: | Duration of Response |
Time Frame: | 1 year |
Safety Issue: | |
Description: | To assess the duration (days) of response from initial response until disease relapse or progression |
Measure: | Progression-free Survival |
Time Frame: | 1 year |
Safety Issue: | |
Description: | To assess the duration (days) of response from Day 0 to disease progression or death |
Measure: | Overall Survival |
Time Frame: | 1 year |
Safety Issue: | |
Description: | To assess the duration (days) of response from Day 0 to death |
Measure: | Time to next treatment |
Time Frame: | 1 year |
Safety Issue: | |
Description: | To assess the duration (days) of response from Day 0 to institution of next therapy |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Precision BioSciences, Inc. |
Last Updated
April 20, 2021