Relapsed or Refractory CD19+ B-cell Lymphoma, Relapsed or Refractory Chronic Lymphocytic Leukemia, Relapsed or Refractory Small Lymphocytic Lymphoma
Conditions
Keywords
CD19+ B-cell Lymphoma, Chronic Lymphocytic Leukemia, CLL, Small Lymphocytic Lymphoma, SLL, Lymphoma, TBI-2001, Anti-CD19 CAR Expressing T cell Therapy, CD19 CAR Gene-Transduced Lymphocyte, Adoptive Immunotherapy, Genetically Engineered Lymphocyte Therapy, Retroviral Vector, Neoplasms by Histologic Type, Neoplasms, Neoplasms, Experimental, Immune System Diseases, Chimeric Antigen Receptor
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).
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
Interventions
BIOLOGICALTBI-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.
DRUGCyclophosphamide
IV Cyclophosphamide (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.
DRUGFludarabine
IV Fludarabine (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.
Sponsors
University Health Network, Toronto
Takara Bio Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 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. 2. Phase Ib cohort will enroll CLL/SLL patients only. 3. ECOG Performance Status 0 or 1. 4. Age ≥18 years at time of consent. 5. Life expectancy greater than 4 months. 6. For cessation of therapies prior to apheresis and lymphodepleting chemotherapy (bridging therapies), the institutional (UHN) SOPs related to Kymriah will be followed. However, an exception will be made for targeted and biological therapies that decrease circulating disease and are not expected to negatively impact successful harvest of lymphocytes by apheresis. In these cases, after discussion with and approval by the Sponsor, no washout will be required. 7. Patients must have adequate key organ function (bone marrow, heart, lung, liver, renal, etc) 8. Consent must be appropriately obtained in accordance with applicable local and regulatory requirements. 9. 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
1. Uncontrolled intercurrent illnesses or medical conditions that may interfere with trial participation. 2. Active or prior documented autoimmune disease within the past 2 years. 3. History of primary immunodeficiency. 4. History of organ transplant that requires use of immunosuppressive medications. 5. History hypersensitivity to components of manufacture or excipients of investigational drug. 6. Untreated central nervous system (CNS) metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids. 7. Other invasive malignancy within 2 years except for noninvasive malignancies 8. Current or prior use of immunosuppressive medication within 14 days before apheresis. 9. 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. 10. Known history of untreated active tuberculosis. 11. HIV positivity. 12. Active HTLV or syphilis infection. 13. Active hepatitis B or active hepatitis C. Subjects with a negative PCR assay for viral load for hepatitis B or C are permitted. 14. Pregnant or lactating women. 15. Received allogeneic-HSCT. 16. Any prior CD19 directed therapy. 17. Live vaccine within 28 days prior to apheresis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of TBI-2001 | One month | Dose Limiting Toxicities (DLTs) |
| Recommended phase 2 dose (RP2D) of TBI-2001 | One year | RP2D to be determined during the dose escalation cohort |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Canada
Contacts
CONTACTMarcus Butler, M.D.
PRINCIPAL_INVESTIGATORMarcus Butler, M.D.
Princess Margaret Cancer Centre
Outcome results
None listed