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

Phase 1

Recruiting

• Conditions: Relapsed or Refractory CD19+ B-cell Lymphoma; Relapsed or Refractory Chronic Lymphocytic Leukemia; Relapsed or Refractory Small Lymphocytic Lymphoma
• Interventions: Biological: TBI-2001; Drug: Cyclophosphamide; Drug: Fludarabine

• Registration Number: NCT05963217
• Lead Sponsor: University Health Network, Toronto

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

Study Timeline

• Study First Submitted: 2023-06-27
• Study Start: 2023-07-26
• Study First Submitted QC: 2023-07-26
• Study First Posted: 2023-07-27
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-09
• Last Update Posted: 2024-08-12
• Primary Completion: 2025-03-30
• Study Completion: 2026-05-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 19

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Experimental: Dose Level 1 to 3	TBI-2001	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.
Experimental: Dose Level 1 to 3	Cyclophosphamide	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.
Experimental: Dose Level 1 to 3	Fludarabine	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.

Primary Outcome Measures

Name	Time	Method
Recommended phase 2 dose (RP2D) of TBI-2001	One year	RP2D to be determined during the dose escalation cohort
Safety of TBI-2001	One year	Laboratory testing- RCR appearance and Clonality

Secondary Outcome Measures

Name	Time	Method
Efficacy of TBI-2001; Progression free survival (PFS)	One year	Progression free survival
Efficacy of TBI-2001; Overall Response Rate (ORR)	One year	Overall Response Rate (ORR) (Complete Response (CR)+Partial Response(PR))
Efficacy of TBI-2001; Overall survival (OS)	One year	Overall survival
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

Trial Locations

Locations (1)

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada