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Clinical Trial 19829

Cancer Type: Malignant Hematology
Study Type: Treatment
NCT#: NCT03666000

Phase: Phase I/II
Prinicipal Investigator: Bijal Shah

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Overview

Study Title

A Phase 1/2a, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate the Safety and Clinical Activity of PBCAR0191 in Subjects with Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL)

Summary

Objective

Primary: To evaluate the safety and tolerability of PBCAR0191 in subjects with relapsed/refractory (r/r) Bcell acute lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma (NHL) and find an appropriate dose to optimize safety and efficacy Secondary: To evaluate the clinical activity of PBCAR0191 in subjects with r/r B-ALL and NHL

Treatments

Therapies

Medications

PBCAR0191 (); Pentostatin (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

Inclusion Criteria

  • Participants 18 years or older
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • Patient has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function
  • Criteria for B-ALL:
  • Relapsed or refractory CD19+ B-cell acute lymphoblastic leukemia (B-ALL) that has been confirmed by morphology and/or flow cytometry and/or minimal residual disease testing (acceptable for enrollment if CD19 expression is confirmed)
  • 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 B-ALL Salvage 2 only (Phase 2a Arm A):
  • Must have previously been treated with initial chemotherapy, with or without subsequent maintenance therapy, had disease progression/relapse, and then have been treated with a second line chemotherapy regimen. Patient does not have refractory disease or relapse after second line chemotherapy but does have evaluable disease demonstrated by MRD assay. Up to 20% blast replacement in the bone marrow by morphology or flow cytometry is allowable in this Arm. If >20% blast replacement, subject is eligible for Phase 1 or Phase 2a Arm B.
  • Criteria for NHL:
  • Relapsed refractory CD19+ B-cell NHL that is histologically confirmed by archived tumor biopsy tissue from last relapse and corresponding pathology report
  • Received at least 2 prior chemotherapy-containing regimens consistent with standard of care treatment guidance (e.g. NCCN) Patients with CLL/SLL must have previously failed at least 2 lines of chemotherapy/ immunotherapy that included ibrutinib plus rituximab Other than those specifically prohibited, other therapies are allowed until 7 days prior to initiation of lymphodepletion. In that case, all screening safety laboratories and disease assessments must be performed after the last dose of prior therapy. For Richter's transformation, only 1 prior line of therapy is required for the DLBCL component.
  • Measurable or detectable disease according to the Lugano Classification
  • Other criteria apply

  • Exclusion Criteria

    Medical conditions

  • Criteria for B-ALL:
  • Burkitt cell (L3 B-ALL) or mixed-lineage acute leukemia.
  • No active CNS disease. Patients with a history of CNS involvement must have a documented CR on at least 2 imaging studies at least 3 months apart (with no masses in parenchyma and no ocular involvement) and a negative CSF cytology on at least 2 evaluations (one evaluation may be during the Screening Period and the other must be at least 3 months prior).
  • Criteria for NHL:
  • No prior or active CNS disease.
  • Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression.
  • Active hemolytic anemia.
  • Criteria for B-ALL and NHL:
  • Patient has had a 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. In the case of Richter’s transformation, patients may be enrolled with ongoing CLL/SLL.
  • Uncontrolled and serious fungal, bacterial, viral, protozoal, or other infection. Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if the patient is responding to active treatment.
  • Any form of primary immunodeficiency (e.g., severe combined immunodeficiency disease).
  • Active hepatitis B or hepatitis C confirmed by polymerase chain reaction (PCR). Patient positive for inactive hepatitis B is allowed to enroll if on prophylactic treatment.
  • Any known uncontrolled cardiovascular disease at the time of Screening that, in the investigator’s opinion, renders the patient ineligible.
  • History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening.
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  • Presence of a CNS disorder that, in the opinion of the investigator, renders the patient ineligible for treatment.
  • Abnormal findings during the Screening Period or any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the patient’s safety.
  • History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.
  • Active uncontrolled autoimmune disease requiring active immunosuppression at the time of Screening (excluding subjects needing steroids for physiologic replacement). Prior/concomitant therapy
  • Patient has received stem cell transplant within 90 days before Screening.
  • Patient has active GvHD symptoms.
  • Patient has received systemic biologic agent within 28 days of enrollment. Note: this criterion does not apply if the patient has had clear evidence of disease progression after such an agent has been administered. This should be discussed with the medical monitor for confirmation.
  • Participation in noninterventional registries or epidemiological studies is not excluded.
  • Patient has received systemic immunostimulatory agent within 30 days or 5 half-lives before the scheduled PBCAR0191 infusion, whichever is longer. Note: this criterion does not apply if the patient has had clear evidence of disease progression after such an agent has been administered. This should be discussed with the medical monitor for confirmation.
  • Radiotherapy within 4 weeks before Screening should be discussed with monitor and determined on a case-by-case basis.
  • Presence of pleural/peritoneal/pericardial catheter.
  • Patient has received live vaccine within 4 weeks before Screening. Non-live virus vaccines are not excluded. Other exclusions apply

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