Study of TBI-2001(Autologous CD19 Specific Chimeric Antigen Receptor (CAR) Gene-transduced T Lymphocytes) for Relapsed or Refractory CD19+ B-cell Lymphoma, CLL/SLL
Study Details
Study Description
Brief Summary
This is a Phase 1/1b, open-label, dose-escalation study to evaluate the safety and the efficacy of anti-CD19 chimeric antigen receptor (CAR) (TBI-2001) for relapsed or refractory CD19+ B-cell lymphoma Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
TBI-2001 is a next-generation CAR-T product including costimulatory sequences that lead to the activation of cytokine-related JAK/STAT signaling pathways. This is a first-in-human study of TBI-2001 and will follow a 3+3 design of dose-escalation cohorts. Additional subjects will be treated with TBI-2001 at the determined recommended phase 2 dose (RP2D) following cyclophosphamide and fludarabine pre-treatment. Long-term follow-up is conducted for 5 years following the infusion of TBI-2001
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Experimental: Dose Level 1 to 3 0.3 to 3 x 10^6 autologous CD19-CAR-T cells/kg per patient will be administered intravenously after a conditioning chemotherapy with cyclophosphamide and fludarabine. |
Biological: TBI-2001
Phase-I portion:
cohort 1: 3×10^5 cells/kg, cohort 2: 1×10^6 cells/kg, cohort 3: 3×10^6 cells/kg). Phase-Ib portion: The dose of Phase-Ib will be determined during the phase I portion.
Drug: Cyclophosphamide
IV Cyclophosphamide (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.
Drug: Fludarabine
IV Fludarabine (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.
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Outcome Measures
Primary Outcome Measures
- Safety of TBI-2001 [One month]
Dose Limiting Toxicities (DLTs)
- Safety of TBI-2001 [One year]
Adverse event (AEs)
- Safety of TBI-2001 [One year]
Laboratory testing- RCR appearance and Clonality
- Recommended phase 2 dose (RP2D) of TBI-2001 [One year]
RP2D to be determined during the dose escalation cohort
Secondary Outcome Measures
- Efficacy of TBI-2001; Overall Response Rate (ORR) [One year]
Overall Response Rate (ORR) (Complete Response (CR)+Partial Response(PR))
- Efficacy of TBI-2001; Durable Response Rate (DRR) [One year]
Durable Response Rate (DRR) as defined as CR or PR sustained for at least 6 months
- Efficacy of TBI-2001; Progression free survival (PFS) [One year]
Progression free survival
- Efficacy of TBI-2001; Overall survival (OS) [One year]
Overall survival
Other Outcome Measures
- Persistence of TBI-2001 [One year]
Percentage of CAR T in peripheral blood and bone marrow using PCR and Flow cytometry.
- Minimal residual disease (MRD) negative rate (in CLL patients) [One year]
MRD negative rate
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients with histologically or cytologically confirmed CD19 positive B cell Non-Hodgkin Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), or Small Lymphocytic Lymphoma (SLL) who have received at least 2 prior therapies.
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Phase Ib cohort will enroll CLL/SLL patients only.
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ECOG Performance Status 0 or 1.
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Age ≥18 years at time of consent.
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Life expectancy greater than 4 months.
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No anti-cancer chemotherapy, radiation therapy or immunotherapy within 2 weeks prior to apheresis for generation of TBI-2001.
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Patients must have adequate key organ function (bone marrow, heart, lung, liver, renal, etc)
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Consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
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The treating investigator should consider the patient to have disease that is incurable, and that the patient would be a reasonable candidate for future treatment with TBI-2001 within the next 3 months
Exclusion Criteria:
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Uncontrolled intercurrent illnesses or medical conditions that may interfere with trial participation.
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Active or prior documented autoimmune disease within the past 2 years.
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History of primary immunodeficiency.
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History of organ transplant that requires use of immunosuppressive medications.
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History hypersensitivity to components of manufacture or excipients of investigational drug.
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Untreated central nervous system (CNS) metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids.
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Other invasive malignancy within 2 years except for noninvasive malignancies
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Current or prior use of immunosuppressive medication within 14 days before apheresis.
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Any condition that, in the opinion of the investigator, would interfere with the evaluation of TBI-2001 or interpretation of subject safety or study results.
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Known history of untreated active tuberculosis.
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HIV positivity.
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Active HTLV or syphilis infection.
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Active hepatitis B or active hepatitis C. Subjects with a negative PCR assay for viral load for hepatitis B or C are permitted.
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Pregnant or lactating women.
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Received allogeneic-HSCT.
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Any prior CD19 directed therapy.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Princess Margaret Cancer Centre | Toronto | Ontario | Canada | M5G 2M9 |
Sponsors and Collaborators
- University Health Network, Toronto
- Takara Bio Inc.
Investigators
- Principal Investigator: Marcus Butler, M.D., Princess Margaret Cancer Centre
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TBI-200101