NCT04223765

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.

Recruiting now Phase 1 Last updated 20 January 2026

What this trial tests

Phase 1 trial testing CAR.k.28 in Mantle Cell Lymphoma in 20 participants. Currently enrolling.

Timeline

12 November 2020

Primary endpoint
22 March 2028

22 March 2043

Quick facts

Lead sponsor	UNC Lineberger Comprehensive Cancer Center
Phase	Phase 1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	20
Start date	12 November 2020
Primary completion	22 March 2028
Estimated completion	22 March 2043
Sites	1 location across United States

Drugs / interventions tested

• CAR.k.28 — full drug profile →
• Fludarabine (FLUDARABINE) — full drug profile →
• Cyclophosphamide (cyclophosphamide) — full drug profile →
• Bendamustine (BENDAMUSTINE) — full drug profile →

Conditions studied

• Mantle Cell Lymphoma — all drugs for Mantle Cell Lymphoma →
• Follicular Lymphoma — all drugs for Follicular Lymphoma →
• Splenic Marginal Zone Lymphoma — all drugs for Splenic Marginal Zone Lymphoma →
• Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue — all drugs for Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue →

Sponsor

UNC Lineberger Comprehensive Cancer Center — full company profile →

Who can join

18 and older, any sex, with Mantle Cell Lymphoma or Follicular Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This study will combine both T cells and antibodies in order to create a more effective treatment. The treatment tested in this study uses modified T-cells called Autologous T Lymphocyte Chimeric Antigen Receptor (ATLCAR) cells targeted against the kappa light chain antibody on cancer cells. For this study, the anti-kappa light chain antibody has been changed so instead of floating free in the blood, a part of it is now joined to the T cells. Only the part of the antibody that sticks to the lymphoma cells is attached to the T cells. When an antibody is joined to a T cell in this way, it is called a chimeric receptor. The kappa light chain chimeric (combination) receptor-activated T cells are called ATLCAR.κ.28 cells. These cells may be able to destroy lymphoma cancer cells. They do not, however, last very long in the body so their chances of fighting the cancer are unknown.

Previous studies have shown that a new gene can be put into T cells to increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes make up the chemical structure carrying your genetic information that may determine human characteristics (i.e., eye color, height and sex). The new gene that is put in the T cells in this study makes an antibody called an anti-kappa light chain. This anti-kappa light chain antibody usually floats around in the blood. The antibody can detect and stick to cancer cells called lymphoma cells because they have a substance on the outside of the cells called kappa light chains.

The purpose of this study is to determine whether receiving the ATLCAR.κ.28 cells is safe and tolerable and learn more about the side effects and how effective these cells are in fighting lymphoma. Initially, the study doctors will test different doses of the ATLCAR.κ.28, to see which dose is safer for use in lymphoma patients. Once a safe dose is identified, the study team will administer this dose to more patients, to learn about how these cells affect lymphoma cancer cells and identify other side effects they might have on the body.

This is the first time ATLCAR.κ.28 cells are given to patients with lymphoma. The Food and Drug Administration (FDA), has not approved giving ATLCAR.κ.28 as treatment for lymphoma. This is the first step in determining whether giving ATLCAR.κ.28 to others with lymphoma in the future will help them.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Emerging Therapies in CLL in the Era of Precision Medicine.
   Iyer P, Wang L. · · 2023 · cited 21× · PMID 36900373 · DOI 10.3390/cancers15051583
2. Immunotherapeutic Strategies in Chronic Lymphocytic Leukemia: Advances and Challenges.
   Perutelli F, Jones R, Griggio V, Vitale C, et al · · 2022 · cited 20× · PMID 35265527 · DOI 10.3389/fonc.2022.837531
3. Tumor Microenvironment and Immunotherapy-Based Approaches in Mantle Cell Lymphoma.
   Saleh K, Cheminant M, Chiron D, Burroni B, et al · · 2022 · cited 18× · PMID 35804999 · DOI 10.3390/cancers14133229
4. CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells.
   Ranganathan R, Shou P, Ahn S, Sun C, et al · · 2021 · cited 16× · PMID 33858858 · DOI 10.1158/1078-0432.ccr-20-2754
5. A Review of Chimeric Antigen Receptor T-Cell Therapy for Myeloma and Lymphoma.
   Atrash S, Moyo TK. · · 2021 · cited 11× · PMID 33814917 · DOI 10.2147/ott.s242018
6. Recent Advances in CAR T-Cell Therapy for Patients with Chronic Lymphocytic Leukemia.
   Heyman BM, Tzachanis D, Kipps TJ. · · 2022 · cited 9× · PMID 35406490 · DOI 10.3390/cancers14071715
7. Mendelian randomization of immune cell phenotypes to discover potential drug targets for B-cell malignancy.
   Beer SA, Went M, Mills C, Wood C, et al · · 2025 · cited 5× · PMID 40199857 · DOI 10.1038/s41408-025-01277-x
8. Cellular Therapies in Chronic Lymphocytic Leukemia and Richter's Transformation: Recent Developments in Chimeric Antigen Receptor T-Cells, Natural Killer Cells, and Allogeneic Stem Cell Transplant.
   Coombs CC, Easaw S, Grover NS, O'Brien SM. · · 2023 · cited 5× · PMID 36980726 · DOI 10.3390/cancers15061838