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

• Status: Recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Precision BioSciences, Inc.
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate

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