Kappa CD28 T Cells for Leukemia

(CHARKALL Trial)

Not currently recruiting at 1 trial location
VT
CR
Overseen ByCarlos Ramos, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for individuals whose cancer—specifically Non-Hodgkin Lymphoma (NHL), Multiple Myeloma (MM), or Chronic Lymphocytic Leukemia (CLL)—has returned or not responded to existing therapies. The treatment employs kappa-CD28 T cells, a type of engineered immune cell therapy, designed to attack cancer by combining antibodies (proteins that fight infections) with T cells (blood cells that kill tumor cells). This combination aims to work more effectively against cancer. The trial may suit those with NHL, MM, or CLL who have not succeeded with standard treatments and experience specific symptoms like frequent fevers or significant weight loss. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that kappa-CD28 T cells, a form of CAR T-cell therapy, hold potential for treating certain cancers such as B-cell lymphoma, chronic lymphocytic leukemia (CLL), and multiple myeloma. These specially modified T cells are combined with antibodies and a protein that aids their growth, and they have undergone safety testing at various doses.

For B-cell lymphoma, studies indicate that CAR T-cells are generally well-tolerated. Researchers have observed positive effects in older patients, suggesting the treatment's safety. Any side effects have been managed effectively, supporting its safety profile.

In CLL, research suggests that CAR T-cell therapy can benefit patients who haven't responded to other treatments. Although specific safety details are not provided, ongoing research indicates it is safe enough to continue studying.

For multiple myeloma, CAR T-cell therapy represents a significant advancement. While detailed safety information is unavailable, continued research and discussions suggest it is considered safe enough for further testing.

Overall, previous studies have demonstrated that different doses of kappa-CD28 T cells were safe for patients. As this treatment remains in early testing, initial safety data is promising, but more research is needed to confirm these findings.12345

Why do researchers think this study treatment might be promising?

Researchers are excited about Kappa CD28 T cells for leukemia because they offer a novel approach by harnessing the body's own immune system to target cancer cells. Unlike traditional treatments such as chemotherapy and radiation, which can affect healthy cells, these engineered T cells are designed to specifically recognize and attack cancerous B cells in conditions like B-CLL, B-cell lymphoma, and myeloma. This targeted action could potentially lead to more effective treatments with fewer side effects. Additionally, the flexibility of adjusting dose levels allows for tailored treatment, maximizing effectiveness while minimizing risks.

What evidence suggests that Kappa CD28 T cells might be an effective treatment for leukemia?

Research has shown that CAR T-cell therapy, which includes kappa CD28 T cells, holds promise in fighting cancers such as chronic lymphocytic leukemia (CLL), B-cell lymphoma, and multiple myeloma. In this trial, participants will receive kappa CD28 T cells specifically for one of these conditions. These specially modified T cells can locate and attack cancer cells, offering potential benefits even when other treatments have failed. For CLL, CAR T-cell therapy has helped patients unresponsive to other treatments. In B-cell lymphoma, this therapy proves effective, particularly for older patients with certain types of the disease. For multiple myeloma, CAR T-cell therapy is considered groundbreaking, with positive results from several studies. The kappa CD28 T cells are designed to target specific proteins on cancer cells, potentially leading to longer-lasting and more effective treatment outcomes.12346

Who Is on the Research Team?

CR

Carlos Ramos, MD

Principal Investigator

Baylor College of Medicine - Texas Children's Hospital

Are You a Good Fit for This Trial?

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

My Coombs test is negative and I have CLL.
I agree to use effective birth control during and for 3 months after the study.
My cancer is a type of B-cell cancer or multiple myeloma with Kappa-light chain.
See 15 more

Exclusion Criteria

My tumor is located where it could block my airway if it grows.
You have an autoimmune disease that is currently causing symptoms or needing treatment.
I am currently taking antibiotics for an infection.
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Patients may receive cyclophosphamide and fludarabine to decrease T cell levels before infusion

1 week

Treatment

Patients receive an infusion of kappa-CD28 T cells at least 24 hours after chemotherapy

1 day
1 visit (in-person)

Evaluation

Patients are evaluated for response to treatment through radiological studies, physical exam, and/or symptoms

4-6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Long-term follow-up

Participants are followed for long-term side effects of gene transfer

15 years

What Are the Treatments Tested in This Trial?

Interventions

  • Kappa CD28 T cells
Trial Overview The study tests kappa-CD28 T cells designed to fight cancer by combining antibodies with T lymphocytes. The highest safe dose found in earlier phases will be used. These engineered T cells carry an antibody that targets cancer cells and a protein (CD28) expected to enhance their longevity and effectiveness.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Group I: Kappa CD28 T cells for myelomaExperimental Treatment1 Intervention
Group II: Kappa CD28 T cells for B-cell lymphomaExperimental Treatment1 Intervention
Group III: Kappa CD28 T cells for B-CLLExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials
1,044
Recruited
6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials
299
Recruited
82,500+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials
114
Recruited
2,900+

Published Research Related to This Trial

CAR T-cell therapy shows promise in improving outcomes for patients with acute myeloid leukemia (AML), a condition with historically poor prognosis.
A significant challenge for the effectiveness of CAR T-cell therapy in AML is the identification of specific target antigens on leukemia cells, as well as the risk of immune escape due to changes in these antigens and a suppressive tumor environment.
Current challenges for CAR T-cell therapy of acute myeloid leukemia.Sauer, T., Rooney, CM.[2020]
In a phase I trial involving 12 younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia, the use of chimeric antigen receptor T cells targeting CD19 and CD22 showed manageable toxicity levels.
Out of the 12 patients, 5 achieved complete responses, indicating promising efficacy of this treatment approach in this challenging patient population.
Targeting CD19-CD22 Aids Younger Patients with ALL.[2021]
In a study testing CD33-CAR NK cells in patients with relapsed and refractory acute myeloid leukemia (AML), no significant adverse effects were observed at doses up to 5 billion cells per patient, suggesting a favorable safety profile.
CAR NK-92 cells can be produced at a lower cost than CAR T cells, indicating that with further optimization, they could become a more accessible treatment option for cancer patients.
First-in-man clinical trial of CAR NK-92 cells: safety test of CD33-CAR NK-92 cells in patients with relapsed and refractory acute myeloid leukemia.Tang, X., Yang, L., Li, Z., et al.[2021]

Citations

Study of Kappa Chimeric Antigen Receptor (CAR) T ...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 ...
Chimeric Antigen Receptor T-cell Therapy for Chronic ...Emerging data appear to show a therapeutic benefit of CAR T-cell therapy in patients with R/R CLL, even after failing an allo-HCT.
Driving Out Chronic Lymphocytic Leukemia With CAR T CellsIn this comprehensive review we explore novel targets for CAR T cell therapy in CLL and highlight the promising results of CAR T cell trials reported to date.
Chimeric Antigen Receptor T-cell Therapy for Chronic ...Emerging data appear to show a therapeutic benefit of CAR T-cell therapy in patients with R/R CLL, even after failing an allo-HCT.
Chimeric antigen receptor-modified T cell therapy in chronic ...In this review, we describe the structure of chimeric antigen receptor, the preclinical, and clinical results of CAR-T therapy against CLL, ...
CAR T cells (kappa-CD28) to treat chronic lymphocytic ...To find out if CAR T cells are safe and work well to treat CLL, B-cell lymphoma or multiple myeloma.
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