Kappa CD28 T Cells for Leukemia
(CHARKALL Trial)
Trial Summary
What is the purpose of this trial?
Patients have a type of cancer called NHL, Multiple Myeloma (MM) or CLL that has come back or has not gone away after treatment. There is no standard treatment for the cancer at this time or the currently used treatments do not work completely in all cases like these. This is a gene transfer research study using special immune cells. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, that investigators hope will work together. Antibodies are types of proteins that protect the body from bacterial and other diseases. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells. Both antibodies and T cells have been used to treat patients with cancers; they have shown promise, but have not been strong enough to cure most patients. The antibody used in this study recognizes a protein on the lymphoma, MM or CLL cells called kappa immunoglobulin. Antibodies can stick to lymphoma, MM or CLL cells when it recognizes the kappa molecules present on the tumor cells. For this study, the kappa antibody has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These chimeric receptor-T cells seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are limited. In the laboratory, investigators found that T cells work better if they also add a protein that stimulates T cells to grow called CD28. By joining the anti-kappa antibody to the T cells and adding the CD28, the investigators expect to be able to make cells that will last for a longer time in the body (because of the presence of the CD28). They are hoping this will make the cells work better. Previously, when patients enrolled on this study, they were assigned to one of three different doses of the kappa-CD28 T cells. We found that all three dose levels are safe. Now, the plan is to give patients the highest dose that we tested. These chimeric T cells (kappa-CD28) are an investigational product not approved by the FDA.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that PD1/PDL1 inhibitors are allowed if medically indicated, suggesting some medications might be permitted.
What data supports the effectiveness of the treatment Kappa CD28 T cells for leukemia?
Chimeric antigen receptor (CAR) T-cell therapies, similar to Kappa CD28 T cells, have shown promise in treating various types of leukemia, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). For instance, CAR T-cells targeting CD19 have led to complete remission in some patients with ALL, and anti-CD123 CAR T-cells have been effective against AML cells.12345
Is Kappa CD28 T cell therapy generally safe for humans?
CAR T cell therapy, which includes Kappa CD28 T cells, has shown effectiveness in treating certain leukemias, but it can cause serious side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). Researchers are working on strategies to reduce these risks and improve safety.678910
How is the Kappa CD28 T cells treatment different from other leukemia treatments?
Research Team
Carlos Ramos, MD
Principal Investigator
Baylor College of Medicine - Texas Children's Hospital
Eligibility Criteria
This trial is for patients with certain blood cancers (NHL, MM, CLL) that have relapsed or are treatment-resistant. Participants must be recovered from prior chemotherapy effects, not HIV positive, and willing to use effective birth control. They should have a life expectancy of at least 12 weeks and no recent history of other cancers or active infections.Inclusion Criteria
Exclusion Criteria
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
Pre-treatment
Patients may receive cyclophosphamide and fludarabine to decrease T cell levels before infusion
Treatment
Patients receive an infusion of kappa-CD28 T cells at least 24 hours after chemotherapy
Evaluation
Patients are evaluated for response to treatment through radiological studies, physical exam, and/or symptoms
Follow-up
Participants are monitored for safety and effectiveness after treatment
Long-term follow-up
Participants are followed for long-term side effects of gene transfer
Treatment Details
Interventions
- Kappa CD28 T cells (CAR T-cell Therapy)
Find a Clinic Near You
Who Is Running the Clinical Trial?
Baylor College of Medicine
Lead Sponsor
Paul Klotman
Baylor College of Medicine
Chief Executive Officer since 2010
MD, PhD
James Versalovic
Baylor College of Medicine
Chief Medical Officer since 2020
MD from Baylor College of Medicine
The Methodist Hospital Research Institute
Collaborator
Dr. John P. Cooke
The Methodist Hospital Research Institute
Chief Medical Officer since 2013
MD, PhD
Dr. Jenny Chang
The Methodist Hospital Research Institute
Chief Executive Officer
MBBChir from University of Cambridge, MHCM from Johns Hopkins University
Center for Cell and Gene Therapy, Baylor College of Medicine
Collaborator
Dr. Helen E. Heslop
Center for Cell and Gene Therapy, Baylor College of Medicine
Chief Executive Officer since 2017
M.D. from University of Otago, New Zealand
Dr. Chrystal U. Louis
Center for Cell and Gene Therapy, Baylor College of Medicine
Chief Medical Officer since 2024
M.D. from Tulane University School of Medicine