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

Relapsed or Refractory Chronic Lymphocytic Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05963217
• Other study ID #: TBI-200101
• Status: Recruiting
• Phase: Phase 1
• Start date: July 26, 2023
• Est. completion date: May 30, 2026

Study information

• Verified date: March 2024
• Source: University Health Network, Toronto
• Contact: Marcus Butler, M.D.
• Phone: 416-946-4501
• Email: tip[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 19
• Est. completion date: May 30, 2026
• Est. primary completion date: March 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Yescarta will be followed.

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.

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Relapsed or Refractory Chronic Lymphocytic Leukemia
• Relapsed or Refractory Small Lymphocytic Lymphoma

Intervention

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.
• Fludarabine
IV Fludarabine (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	Takara Bio Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Persistence of TBI-2001	Percentage of CAR T in peripheral blood and bone marrow using PCR and Flow cytometry.	One year
Other	Minimal residual disease (MRD) negative rate (in CLL patients)	MRD negative rate	One year
Primary	Safety of TBI-2001	Dose Limiting Toxicities (DLTs)	One month
Primary	Safety of TBI-2001	Adverse event (AEs)	One year
Primary	Safety of TBI-2001	Laboratory testing- RCR appearance and Clonality	One year
Primary	Recommended phase 2 dose (RP2D) of TBI-2001	RP2D to be determined during the dose escalation cohort	One year
Secondary	Efficacy of TBI-2001; Overall Response Rate (ORR)	Overall Response Rate (ORR) (Complete Response (CR)+Partial Response(PR))	One year
Secondary	Efficacy of TBI-2001; Durable Response Rate (DRR)	Durable Response Rate (DRR) as defined as CR or PR sustained for at least 6 months	One year
Secondary	Efficacy of TBI-2001; Progression free survival (PFS)	Progression free survival	One year
Secondary	Efficacy of TBI-2001; Overall survival (OS)	Overall survival	One year