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.

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

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18+

SponsorUNC Lineberger Comprehensive Cancer Center

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Written informed consent and HIPAA authorization for release of personal health information.

Adults ≥18 years of age.

DLBCL not otherwise specified (NOS)

T cell/histiocyte rich large B cell lymphoma; primary cutaneous DLBCL, leg type; EBV-positive DLBCL NOS; DLBCL associated with chronic inflammation; Lymphomatoid granulomatosis; Large B-cell lymphoma with IRF4 rearrangement; Intravascular large B-cell lymphoma; ALK-positive large B-cell lymphoma

Disqualifiers

Subject has signed a consent to undergo cell procurement.

Total bilirubin <1.5 × ULN (subjects with Gilbert's syndrome may be enrolled despite a total bilirubin level >1.5 mg/dL if their conjugated bilirubin is <1.5 × ULN)

AST and ALT < 5x ULN

Pulse oximetry of >90% on room air

Trial design

Design model

Single group

Treatments tested in this trial

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.

Treatment groups

20 Participants

are divided into 1 treatment group

Group A: CAR.k.28/CAR.k.4-1BBExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

Number of participants with adverse events as a measure of safety and tolerability of CAR.κ.28 ATL cells

Toxicity is classified and graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). Grade 1 Mild; asymptomatic or mild symptoms; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to Adverse Event (AE). Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded per American Society for Blood and Marrow Transplantation (ASBMT) ICANS Consensus Grading for Adults (scale from 1-mild to 4-critical) and cytokine release syndrome (CRS) symptoms will be graded according to ASBMT CRS Consensus Grading (a scale from 1-mild to 5-death).

Time frame

4 weeks

Secondary outcomes

Progression free survival (PFS) after infusion of CAR.κ.28 cells

PFS is defined from the date of administration of CAR.κ.28 infusion to progression, or death as a result of any cause per revised Lugano criteria for Non-Hodgkin Lymphoma (NHL) and International Workshop on Chronic Lymphocytic Leukemia (IWCLL) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL).

Time frame

15 years

Overall survival (OS) after administration of CAR.κ.28 cells

Overall survival will be measured from the date of administration of CAR.κ.28 infusion to date of death

Time frame

15 years

Objective response rate by 8 weeks and best overall response rate post CAR.κ.28 cell administration

The objective response rate will be defined as the rate of complete responses (CR) + partial responses (PR) by 8 weeks post CAR.κ.28 infusion per revised Lugano criteria for Non-Hodgkin Lymphoma (NHL). For Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) patients, the rate of CR + PR will be defined by the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria by 8 weeks post-CAR.κ.28 infusion

Time frame

8 weeks

Other outcomes

Duration of response after administration of CAR.κ.28 cells

The duration of response will be defined as time from documentation of tumor response per Lugano criteria for Non-Hodgkin Lymphoma (NHL) or International Workshop on Chronic Lymphocytic Leukemia (IWCLL) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL).

Time frame

15 years

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

UNC Lineberger Comprehensive Cancer Center

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov

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