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.

Conditions

• Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
• Follicular Lymphoma
• Indolent Non-hodgkin Lymphoma
• Mantle Cell Lymphoma
• Nodal Marginal Zone Lymphoma
• Splenic Marginal Zone Lymphoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• CAR.k.28 — DRUG
  Three dose levels will be evaluated: Dose level 1 (5x10\^5 cells/kg), Dose level 2 (1x10\^6), and dose level 3 (2x10\^6 cells/kg).
• Fludarabine — DRUG
  30 mg/m\^2/day IV for 3 consecutive days
• Cyclophosphamide — DRUG
  500 mg/m\^2/day IV for 3 consecutive days
• Bendamustine — DRUG
  70 mg/m\^2/day administered over 3 consecutive days.

Study Details

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.

Key Dates

Start date

Nov 12, 2020

Status verified

Jan 2026

Primary completion

Mar 22, 2028

Completion

Mar 22, 2043

Study Design

Enrollment

20 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: CAR.k.28/CAR.k.4-1BB
  Up to 12 patients will receive a single infusion of CAR.k.28. The starting dose will be 2.5x10\^5 cells/kg of each product. Up to 3 dose levels of CAR.k.28 cells will be tested with at least 3 patients enrolled at each dose cohort before dose escalation is considered based on the incidence of dose limiting toxicity (DLT). An expansion cohort will enroll up to 8 patients at the recommended phase 2 dose. Prior to receiving the infusions, patients will undergo lymphodepletion with fludarabine and bendamustine. Patients with a known history of intolerance to bendamustine may be considered for lymphodepletion with fludarabine and cyclophosphamide.

Primary Outcome Measure

Number of participants with adverse events as a measure of safety and tolerability of CAR.κ.28 ATL cells [ Time Frame: 4 weeks ]

Central Contacts

• Catherine Cheng
  919-445-4208
  [email protected]
• Kelly Hoye
  919-445-9676
  [email protected]

Locations (1)

Find similar trials in Chapel Hill, NC

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