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

June 5, 2026 updated by: University Health Network, Toronto

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)

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

19

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Marcus Butler, M.D.
  • Phone Number: 2911 416-946-4501
  • Email: tip@uhn.ca

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • Princess Margaret Cancer Centre
        • Contact:
        • Principal Investigator:
          • Marcus Butler, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
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.
Drug: Fludarabine
IV Fludarabine (for 3 days) will be administered as conditioning before cell infusion with TBI-2001.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of TBI-2001
Time Frame: One month
Dose Limiting Toxicities (DLTs)
One month
Safety of TBI-2001
Time Frame: One year
Adverse event (AEs)
One year
Safety of TBI-2001
Time Frame: One year
Laboratory testing- RCR appearance and Clonality
One year
Recommended phase 2 dose (RP2D) of TBI-2001
Time Frame: One year
RP2D to be determined during the dose escalation cohort
One year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of TBI-2001; Overall Response Rate (ORR)
Time Frame: One year
Overall Response Rate (ORR) (Complete Response (CR)+Partial Response(PR))
One year
Efficacy of TBI-2001; Durable Response Rate (DRR)
Time Frame: One year
Durable Response Rate (DRR) as defined as CR or PR sustained for at least 6 months
One year
Efficacy of TBI-2001; Progression free survival (PFS)
Time Frame: One year
Progression free survival
One year
Efficacy of TBI-2001; Overall survival (OS)
Time Frame: One year
Overall survival
One year

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Persistence of TBI-2001
Time Frame: One year
Percentage of CAR T in peripheral blood and bone marrow using PCR and Flow cytometry.
One year
Minimal residual disease (MRD) negative rate (in CLL patients)
Time Frame: One year
MRD negative rate
One year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Collaborators

Takara Bio Inc.

Investigators

  • Principal Investigator: Marcus Butler, M.D., Princess Margaret Cancer Centre

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 26, 2023

Primary Completion (Estimated)

June 30, 2028

Study Completion (Estimated)

June 30, 2028

Study Registration Dates

First Submitted

June 27, 2023

First Submitted That Met QC Criteria

July 26, 2023

First Posted (Actual)

July 27, 2023

Study Record Updates

Last Update Posted (Actual)

June 9, 2026

Last Update Submitted That Met QC Criteria

June 5, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TBI-200101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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