Actively Recruiting

Phase 1
Age: 18Years +
All Genders
ID04223765

Phase 1 Study of T Lymphocytes with Kappa Chimeric Antigen Receptor and CD28 Endodomain for Relapsed/Refractory Kappa+ Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Led by UNC Lineberger Comprehensive Cancer Center · Updated on 2026-01-20

20

Participants Needed

1

Research Sites

782 weeks

Total Duration

On this page

Sponsors

U

UNC Lineberger Comprehensive Cancer Center

Lead Sponsor

N

National Cancer Institute (NCI)

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are studying a new treatment using modified T cells called Autologous T Lymphocyte Chimeric Antigen Receptor (ATLCAR) cells, which target the kappa light chain antibody on lymphoma cancer cells. This trial aims to determine the safety, side effects, and effectiveness of these ATLCAR.κ.28 cells in treating relapsed or refractory kappa-positive non-Hodgkin lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. This is a phase 1, single-center, open-label trial and the first time these cells are given to patients for this purpose. Participants receive a single infusion of CAR.κ.28 cells at one of three escalating dose levels after undergoing a lymphodepleting chemotherapy regimen with fludarabine and bendamustine or cyclophosphamide. Up to 12 patients will be enrolled in the dose-finding phase, and an expansion cohort of up to 8 patients will receive the recommended phase 2 dose to further assess safety and efficacy. The CAR.κ.28 cells are administered intravenously over 5 to 10 minutes, and bridging chemotherapy may be given while the cells are prepared. During the study, participants undergo blood collection or leukapheresis to obtain cells for CAR.κ.28 production. They will be monitored with laboratory tests, imaging, and assessments of the CAR cells' persistence in the blood. Researchers will evaluate safety primarily by tracking adverse events within 4 weeks and will follow participants for up to 15 years to observe progression-free survival, overall survival, and response rates. Participants will also be followed for adverse events and disease progression throughout the study duration.

CONDITIONS

Brief Title

Study of Kappa Chimeric Antigen Receptor (CAR) T Lymphocytes Co-Expressing the Kappa and CD28 CARs for Relapsed/Refractory Kappa+ Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Adults 18 years of age or older
  • Diagnosis of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma or kappa-positive B-cell non-Hodgkin lymphoma as defined by WHO 2016
  • Subjects relapsed after autologous or allogeneic stem cell transplant are eligible
  • Prior CD19-directed CAR therapy allowed if at least 3 months have passed
  • Aggressive lymphomas require at least 2 prior systemic therapies including anti-CD20 antibody and anthracycline chemotherapy
  • Indolent lymphomas require at least 2 prior lines of therapy
  • Kappa-positive expression confirmed on lymphoma or CLL/SLL tissue or flow cytometry
  • Karnofsky performance score greater than 60%
  • Female subjects of childbearing potential must agree to use two methods of birth control or be surgically sterile, or abstain from heterosexual activity during the study and for 6 months after
Not Eligible

You will not qualify if you...

  • History of intolerance to bendamustine or fludarabine (may consider cyclophosphamide and fludarabine instead)
  • Pregnant or lactating women
  • Current use of systemic corticosteroids at doses of 10 mg prednisone daily or more (less than 10 mg may be allowed at investigator's discretion)
  • Active uncontrolled infection including HTLV, HCV, or history of HIV
  • Evidence of uncontrolled infection or sepsis prior to lymphodepletion and cell infusion
  • Use of prohibited or contraindicated medications listed in the protocol
  • Received tumor vaccines within 6 weeks prior to lymphodepletion
  • Received investigational or cancer-directed therapy within 3 weeks or 5 half-lives prior to lymphodepletion
  • Clinical indication of rapidly progressing disease prior to cell infusion
  • Any condition that makes participant unsuitable for treatment in opinion of investigator

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Run-in Period

Duration - 1 to 2 months

Participants provide peripheral blood for cell procurement up to 3 times to collect T cells for CAR.κ.28 cell production. During the approximately 1 to 2 months needed for cell production, participants may receive standard care treatment as needed.

Up to 3 blood collection visits

Lymphodepleting Chemotherapy

Duration - 3 days

Participants undergo lymphodepleting chemotherapy with bendamustine and fludarabine or, if intolerant to bendamustine, cyclophosphamide and fludarabine to prepare for CAR.κ.28 cell infusion.

3 consecutive daily visits (in-person) for chemotherapy administration

Treatment

Duration - Single day

Participants receive a single infusion of CAR.κ.28 cells at one of three dose levels following lymphodepletion.

1 infusion visit (in-person)

Follow-up

Duration - Up to 15 years

Participants are followed for safety, response, and long-term outcomes including survival and persistence of CAR.κ.28 cells for up to 15 years after treatment.

Regular follow-up visits over several years as per protocol

Trial Site Locations

Total: 1 location

1

Lineberger Comprehensive Cancer Center at University of North Carolina

Chapel Hill, North Carolina, United States, 27599

Actively Recruiting

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Research Team

C

Catherine Cheng

K

Kelly Hoye

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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