Clinical trial NCT05963217: 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
Official title: Phase I/Ib Study of TBI-2001 for Patients With Relapsed or Refractory CD19+ B-cell Lymphoma, Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed or Refractory CD19+ B-cell Lymphoma
Relapsed or Refractory Chronic Lymphocytic Leukemia
Relapsed or Refractory Small Lymphocytic Lymphoma
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
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Takara Bio Inc.
First posted: 2023-07-27
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Safety of TBI-2001
timeFrame: One month
measure: Safety of TBI-2001
timeFrame: One year
measure: Safety of TBI-2001
timeFrame: One year
measure: Recommended phase 2 dose (RP2D) of TBI-2001
timeFrame: One year
Secondary outcomes:
measure: Efficacy of TBI-2001; Overall Response Rate (ORR)
timeFrame: One year
measure: Efficacy of TBI-2001; Durable Response Rate (DRR)
timeFrame: One year
measure: Efficacy of TBI-2001; Progression free survival (PFS)
timeFrame: One year
measure: Efficacy of TBI-2001; Overall survival (OS)
timeFrame: One year
Other outcomes:
measure: Persistence of TBI-2001
timeFrame: One year
measure: Minimal residual disease (MRD) negative rate (in CLL patients)
timeFrame: One year
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Marcus Butler, M.D.
role: PRINCIPAL_INVESTIGATOR
References: