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
PBCAR0191 in adults with r/r B ALL (Cohort A) and in adults with r/r B-cell NHL (Cohort N).
- 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:
- NCT ID:
- Non-Hodgkin Lymphoma
- B-cell Acute Lymphoblastic Leukemia
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).
|PBCAR0191-01||Experimental||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.|
Criteria for B-ALL:
1. Relapsed or refractory CD19+ B-cell acute lymphoblastic leukemia (B-ALL).
2. Philadelphia chromosome positive (Ph+) disease can be eligible if they are intolerant
to tyrosine kinase inhibitor (TKI) therapy or if they have relapsed/refractory
Criteria for NHL:
3. r/r CD19+ B-cell NHL that is histologically confirmed by archived tumor biopsy tissue
from last relapse and corresponding pathology report.
4. Received at least 2 prior chemotherapy-containing regimens.
5. Measurable or detectable disease according to the Lugano Classification.
Criteria for both B-ALL and NHL:
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
7. Estimated life expectancy of at least 12 weeks according to investigator's judgment.
8. Seronegative for HIV antibody (ie, the subject has intact immune function).
9. Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.
10. 18 years of age or older.
11. Any sex.
12. Willing to practice birth control and refrain from donating sperms or oocytes .
13. Women of childbearing potential (WOCBP) must be tested negative for pregnancy at
14. Capable of giving signed informed consent.
Criteria for B-ALL:
1. Burkitt cell (L3 ALL) or mixed-lineage acute leukemia.
2. Evidence of CNS leukemia.
Criteria for NHL:
3. Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or
blood vessel compression.
4. Active hemolytic anemia.
5. Active CNS lymphoma.
Criteria for B-ALL and NHL:
6. Malignancy, besides the malignancies of inclusion (B-ALL or NHL), that in the
Investigator's opinion, has a high risk of relapse in the next 2 years.
7. Uncontrolled and serious fungal, bacterial, viral, protozoal, or other infection.
8. Any form of primary immunodeficiency.
9. Subject has active hepatitis B or hepatitis C.
10. Any known uncontrolled cardiovascular disease at the time of screening that, in the
Investigator's opinion, renders the subject ineligible.
11. History of hypertension crisis or hypertensive encephalopathy within 3 months prior to
12. History of severe immediate hypersensitivity reaction to any of the agents used in
13. Presence of a CNS disorder that renders the subject ineligible for treatment.
14. Abnormal findings during the screening period or any other medical condition(s) or
laboratory findings that might jeopardize the patient's safety.
15. History of concomitant genetic syndrome known bone marrow failure syndrome.
16. Requires active immunosuppression at the time of screening.
17. C-reactive protein (CRP) >15 mg/dL at screening.
18. Received stem cell transplant within 90 days before screening.
19. Active GvHD symptoms.
20. Received blinatumomab or inotuzumab ozogamicin within 30 days of screening.
21. Received systemic immunostimulatory agent within 30 days or 5 half-lives.
22. Radioimmunotherapy within 6 months before screening that may interfere with the
activity of agents in the study.
23. Radiotherapy within 4 weeks before screening should be discussed with monitor.
24. Presence of pleural/peritoneal/pericardial catheter.
25. Received live vaccine within 4 weeks before screening. Non-live virus vaccines are not
26. Current use of any anticoagulant or antiplatelet therapy.
27. Received an anti-PD-1 or anti-PD-L1 antibodies, or other immune modifying therapy.
28. Received any investigational biologic treatment within 30 days or 5 half-lives before
screening, or investigational nonbiologic treatment within 30 days before screening.
29. Pregnant or breastfeeding women.
30. Unlikely to complete all protocol-required study visits or procedures.
31. Any mental condition rendering the subject unable to understand the nature, scope, and
possible consequences of the study, and/or evidence of an uncooperative attitude.
|Maximum Eligible Age:||N/A|
|Minimum Eligible Age:||18 Years|
Primary Outcome Measures
|Measure:||Maximum Tolerated Dose (MTD)|
|Time Frame:||Day 1 - Day 28|
|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|
|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:||Area Under the Curve [AUC]|
|Time Frame:||Up to 1 year|
|Description:||To evaluate Area Under the Curve [AUC] of PBCAR0191 in patients tested.|
|Phase:||Phase 1/Phase 2|
|Overall Status:||Not yet recruiting|
|Lead Sponsor:||Precision BioSciences, Inc.|