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.
Phase 1 Study of the Administration of T Lymphocytes Expressing the Kappa Chimeric Antigen Receptor (CAR) and CD28 Endodomain for Relapsed/Refractory Kappa+ Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma.
2 other identifiers
interventional
20
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Nov 2020
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 7, 2020
CompletedFirst Posted
Study publicly available on registry
January 10, 2020
CompletedStudy Start
First participant enrolled
November 12, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 22, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 22, 2043
January 20, 2026
January 1, 2026
7.4 years
January 7, 2020
January 16, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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).
4 weeks
Secondary Outcomes (3)
Progression free survival (PFS) after infusion of CAR.κ.28 cells
15 years
Overall survival (OS) after administration of CAR.κ.28 cells
15 years
Objective response rate by 8 weeks and best overall response rate post CAR.κ.28 cell administration
8 weeks
Other Outcomes (1)
Duration of response after administration of CAR.κ.28 cells
15 years
Study Arms (1)
CAR.k.28/CAR.k.4-1BB
EXPERIMENTALUp 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.
Interventions
500 mg/m\^2/day IV for 3 consecutive days
70 mg/m\^2/day administered over 3 consecutive days.
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).
Eligibility Criteria
You may qualify if:
- Unless otherwise noted, subjects must meet all of the following criteria to participate in this study:
- Written informed consent and HIPAA authorization for release of personal health information.
- Adults ≥18 years of age.
- Diagnosis of relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma OR histologically confirmed B-cell NHL, including the following types defined by WHO 2016:
- Aggressive Lymphomas:
- 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
- Primary mediastinal (thymic) large B-cell lymphoma
- High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement; high grade B-cell lymphoma, NOS
- B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
- Transformation of indolent lymphoma or CLL to DLBCL will also be included
- Burkitt lymphoma
- Indolent Lymphomas:
- Follicular lymphoma grade 1-3b
- Splenic marginal zone lymphoma
- +20 more criteria
You may not qualify if:
- \. A history of intolerance to bendamustine or fludarabine. Note: subjects with known history of intolerance to bendamustine may be considered for lymphodepletion with cyclophosphamide and fludarabine at the discretion of the clinical investigator.
- Subject is pregnant or lactating. 3 Current use of systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent; those receiving \<10 mg daily may be enrolled at discretion of investigator. 4 Active infection with HTLV, HCV (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) defined as not being well controlled on therapy as well as no history of HIV. Subjects are required to have negative HIV antibody, negative HTLV1 and HTLV2 antibodies, negative hepatitis B surface antigen, and negative HCV antibody or viral load.
- Eligibility Criteria to be Met Prior to Procurement
- Subject has signed a consent to undergo cell procurement.
- Evidence of adequate organ function as defined by:
- 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
- Creatinine ≤ 2 x ULN
- Imaging results from within 120 days prior to procurement to assess presence of active disease.
- Confirmed kappa-positive expression on lymphoma or CLL/SLL tissue or bone marrow sample (archival or fresh) as confirmed by pathology.
- Subject has adequate cardiac function, defined as:
- No ECG evidence of acute ischemia
- No ECG evidence of active, clinically significant conduction system abnormalities
- Prior to study entry, any ECG abnormality at screening not felt to put the subject at risk has to be documented by the investigator as not medically significant
- +35 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Lineberger Comprehensive Cancer Center at University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Natalie Grover, MD
UNC Lineberger Comprehensive Cancer Center
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 7, 2020
First Posted
January 10, 2020
Study Start
November 12, 2020
Primary Completion (Estimated)
March 22, 2028
Study Completion (Estimated)
March 22, 2043
Last Updated
January 20, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share