OncoMatch/Clinical Trials/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.
Is NCT04223765 recruiting? Yes, currently enrolling (May 2026). This Phase 1 trial studies multiple treatments including CAR.k.28 and Fludarabine for mantle cell lymphoma.
Treatment: CAR.k.28 · Fludarabine · Cyclophosphamide · Bendamustine — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Non-Hodgkin Lymphoma
Prior therapy
Must have received: autologous or allogeneic stem cell transplant
Subjects relapsed after autologous or allogeneic stem cell transplant are eligible for this study.
Must have received: CD19-directed CAR-T cell therapy
Subjects who have received prior CD19-directed CAR therapies for relapsed/refractory disease are eligible for this study. However, at least 3 months must have passed since the subject received CD19 CAR-T cells.
Must have received: anti-CD20 monoclonal antibody — aggressive lymphoma
An anti-CD20 monoclonal antibody
Must have received: anthracycline containing chemotherapy regimen — aggressive lymphoma (if eligible)
An anthracycline containing chemotherapy regimen (if eligible)
Must have received: autologous stem cell transplant — aggressive lymphoma (if eligible)
An autologous stem cell transplant (if eligible)
Must have received: alkylating agent and anti-CD20 monoclonal antibody (combination) — CLL/SLL
A combination of an anti-CD20 monoclonal antibody and an alkylating agent
Must have received: Bruton's Tyrosine Kinase Inhibitor — CLL/SLL
A Bruton's Tyrosine Kinase Inhibitor
Must have received: BCL-2 inhibitor and anti-CD20 monoclonal antibody (combination) — CLL/SLL
A BCL-2 inhibitor in combination with an anti-CD20 monoclonal antibody
Cannot have received: bendamustine (bendamustine)
Exception: Subjects with known history of intolerance to bendamustine may be considered for lymphodepletion with cyclophosphamide and fludarabine at the discretion of the clinical investigator.
A history of intolerance to bendamustine
Cannot have received: fludarabine (fludarabine)
A history of intolerance to fludarabine
Lab requirements
Blood counts
ANC >1.0 × 10^9/L; Platelets >50 × 10^9/L unless related to lymphoma involvement
Kidney function
Creatinine ≤ 2 x ULN (or ≤3 x ULN for cell infusion)
Liver function
Total bilirubin <1.5 × ULN (or ≤2 × ULN for cell infusion, unless attributed to Gilbert's syndrome); AST and ALT <5x ULN (or ≤5x ULN for cell infusion)
Cardiac function
No ECG evidence of acute ischemia or clinically significant conduction system abnormalities; LVEF >40% by ECHO; no uncontrolled angina or severe ventricular arrhythmia
Evidence of adequate organ function as defined by: Total bilirubin <1.5 × ULN...AST and ALT < 5x ULN...Creatinine ≤ 2 x ULN...ANC >1.0 × 10^9/L; Platelets >50 × 10^9/L...No ECG evidence of acute ischemia...LVEF >40% by ECHO
Structured fields extracted by AI. May contain errors — verify against the official protocol.
US trial sites
- Lineberger Comprehensive Cancer Center at University of North Carolina · Chapel Hill, North Carolina
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