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.
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|ClinicalTrials.gov Identifier: NCT04223765|
Recruitment Status : Recruiting
First Posted : January 10, 2020
Last Update Posted : April 22, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Mantle 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||Drug: CAR.k.28 Drug: Fludarabine Drug: Cyclophosphamide Drug: Bendamustine||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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.|
|Actual Study Start Date :||November 12, 2020|
|Estimated Primary Completion Date :||December 2023|
|Estimated Study Completion Date :||December 2038|
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.
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).
Other Name: Kappa Chimeric Antigen Receptor and CD28 Endodomain
30 mg/m^2/day IV for 3 consecutive days
Other Name: FLUDARA
500 mg/m^2/day IV for 3 consecutive days
Other Name: Cytoxan
70 mg/m^2/day administered over 3 consecutive days.
Other Name: Bendeka, Treanda
- Number of participants with adverse events as a measure of safety and tolerability of CAR.κ.28 ATL cells [ Time Frame: 4 weeks ]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).
- Median progression free survival (PFS) after infusion of CAR.κ.28 cells [ Time Frame: 15 years ]PFS is defined from day of CAR.κ.28 infusion to relapse (in patients with a documented complete response after conditioning chemotherapy) or progression (in patients without complete response after conditioning chemotherapy), 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).
- Median overall survival (OS) after administration of CAR.κ.28 cells [ Time Frame: 15 years ]Overall survival will be measured from the date of administration of CAR.κ.28 infusion to date of death
- Objective response rate by 8 weeks and best overall response rate post CAR.κ.28 cell administration [ Time Frame: 8 weeks ]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
- Duration of response after administration of CAR.κ.28 cells [ Time Frame: 15 years ]The duration of response will be defined as time from documentation of tumor response to disease progression. Response will be evaluated 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) .
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04223765
|Contact: Catherine Chengfirstname.lastname@example.org|
|Contact: Spencer Laingemail@example.com|
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Catherine Cheng 919-445-4208 firstname.lastname@example.org|
|Contact: Caroline Babinec (919) 962-7426 email@example.com|
|Principal Investigator: Natalie Grover, MD|
|Sub-Investigator: Paul Armistead|
|Sub-Investigator: Anne Beaven, MD|
|Sub-Investigator: James Coghill|
|Sub-Investigator: Christopher Dittus, MD|
|Sub-Investigator: Gianpietro Dotti|
|Sub-Investigator: Paul Eldridge|
|Sub-Investigator: Katarzyna Jamieson|
|Sub-Investigator: Emily Kassam|
|Sub-Investigator: Grace Park|
|Sub-Investigator: Alicia Pinto|
|Sub-Investigator: Marcie Riches|
|Sub-Investigator: Barbara Savoldo|
|Sub-Investigator: Jonathan Serody, MD|
|Sub-Investigator: Thomas Shea, MD|
|Sub-Investigator: Benjamin Vincent|
|Sub-Investigator: Kimberly Wehner|
|Sub-Investigator: William Wood|
|Sub-Investigator: Ashley Zanter|
|Principal Investigator:||Natalie Grover, MD||UNC Lineberger Comprehensive Cancer Center|