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

NCT ID: NCT05963217

Last Updated: 2025-07-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

19 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-26

Study Completion Date

2026-05-30

Brief Summary

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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

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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

Conditions

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Relapsed or Refractory CD19+ B-cell Lymphoma Relapsed or Refractory Chronic Lymphocytic Leukemia Relapsed or Refractory Small Lymphocytic Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

TBI-2001

Intervention Type BIOLOGICAL

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.

Cyclophosphamide

Intervention Type DRUG

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

Fludarabine

Intervention Type DRUG

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

Interventions

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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.

Intervention Type BIOLOGICAL

Cyclophosphamide

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

Intervention Type DRUG

Fludarabine

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Takara Bio Inc.

INDUSTRY

Sponsor Role collaborator

University Health Network, Toronto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Marcus Butler, M.D.

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre

Locations

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Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Marcus Butler, M.D.

Role: CONTACT

416-946-4501 ext. 2911

Facility Contacts

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Marcus Butler, M.D.

Role: primary

416-946-4501 ext. 5485

Other Identifiers

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TBI-200101

Identifier Type: -

Identifier Source: org_study_id

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