90 Participants Needed

CAR-T Cell Therapy for Lymphoma

(CABAL2 Trial)

Recruiting at 1 trial location
VT
Premal Lulla, MD profile photo
Overseen ByPremal Lulla, MD
Age: Any Age
Sex: Any
Trial Phase: Phase 1
Sponsor: Baylor College of Medicine
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you have used certain investigational drugs or therapies recently, or if you are currently using high-dose corticosteroids.

What data supports the effectiveness of the treatment C7R.CD30.CAR-EBVST cells for lymphoma?

Research shows that modifying T-cells with a C7R receptor can enhance their ability to fight tumors, as seen in Epstein-Barr virus-specific T-cells that controlled lymphoma more effectively in a mouse model. Additionally, CAR T-cell therapy, which is part of this treatment, has been effective in treating various types of lymphoma, including Hodgkin lymphoma.12345

Is CAR-T cell therapy generally safe for humans?

CAR-T cell therapy can cause serious side effects, including cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). These side effects can lead to complications like infections or bleeding, and in some cases, they can be life-threatening.678910

How is the C7R.CD30.CAR-EBVST cell treatment different from other lymphoma treatments?

This treatment is unique because it combines a chimeric antigen receptor (CAR) targeting CD30 with Epstein-Barr virus-specific T-cells (EBVSTs) enhanced by a constitutively active IL7 receptor (C7R), which improves the persistence and expansion of the T-cells, potentially leading to better control of lymphoma.123511

What is the purpose of this trial?

This study involves patients that have a cancer called diffuse large B cell lymphoma (DLBCL), Natural killer/T-cell lymphoma (NKTL), or classical Hodgkin lymphoma (cHL) (referred to collectively as lymphoma). Patients' lymphoma has come back or not gone away after treatment.A previous research study at Baylor combined two ways of fighting disease: antibodies and T cells. Antibodies are proteins that bind to bacteria, viruses and other foreign substances to prevent disease. T-cells are special infection-fighting white blood cells that can kill tumor cells or cells infected with bacteria and viruses. Both have shown promise treating cancer, but neither has been strong enough to cure most patients. In the previous study, an antibody called anti-CD30 which is found on the surface of some T-cells and cancer cells, and had been used to treat lymphoma with limited success, was joined to the T-cells through a process called gene transfer, resulting in CD30.CAR T cells.Another study saw encouraging responses using CD30.CAR T cells made in a lab from a patients' own blood then injected back into the same patient to treat their lymphoma. These cells are termed 'autologous' because they're given back to the original patient.In an ongoing study, patients were treated with allogeneic CD30.CAR T cells, which are made from healthy donors instead of the patients. The use of allogenic cells avoids a lengthy manufacture time since the products are stored as a bank and available on demand. This ongoing trial has preliminarily shown promising clinical activity with no safety concerns.With the current study, investigators plan to extend the anti-cancer effects of the CD30.CAR T cell by attaching another molecule called C7R, which has made CAR T cells have deeper and longer anticancer effects in the laboratory. The aim is to study the safety and effectiveness of allogeneic banked CD30.CAR-EBVST cells that also carry the C7R molecule, to learn the side effects of C7R modified CD30.CAR-EBVST cells in lymphoma patients, and to see whether this therapy may help them. As an extra safety step, the C7R containing T cells will also have a marker called iC9. If a patient experiences intolerable side effects from the C7R T cells, they could receive a medication called 'rimiducid' that can eliminate the C7R containing T cells by binding iC9, thereby potentially resolving the side effects. While not yet FDA approved, rimiducid has been tested in patients before without bad side effects.

Research Team

Dr. Premal Lulla in Houston, TX

Premal Lulla, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for patients with certain types of lymphoma, including diffuse large B cell, natural killer/T-cell, or classical Hodgkin lymphoma that has persisted or returned after treatment. Participants must meet specific health criteria not detailed here.

Inclusion Criteria

I have recovered from all major side effects of my previous chemotherapy.
I am between 12 and 75 years old.
My diagnosis is one of the specified types of lymphoma or I have a CD30-positive tumor.
See 7 more

Exclusion Criteria

My tumor is in a place where it could block my breathing if it gets bigger.
I am taking more than 10 mg/day of steroids.
I do not have any serious, uncontrolled infections.
See 6 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
Multiple visits for blood tests, physical examination, and imaging studies

Lymphodepletion Chemotherapy

Participants receive cyclophosphamide and fludarabine to reduce T cell count before infusion

1 week
1 visit (in-person)

Treatment

Participants receive C7R.CD30.CAR-EBVST cell infusion at one of four dose levels

4 weeks
Weekly visits for monitoring post-infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment

15 years
Visits at week 1, 2, 3, 4, 8, every 3 months for 1 year, every 6 months for 4 years, then yearly

Treatment Details

Interventions

  • C7R.CD30.CAR-EBVST cells
Trial Overview The study tests C7R.CD30.CAR-EBVST cells on patients with lymphoma. It aims to improve upon previous CAR T cell therapies by using a modified version that may have longer and stronger effects against cancer.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment PhaseExperimental Treatment1 Intervention
Four dose levels will be evaluated based on safety data from our current study of CD30 CAR T cells. Cohorts of three patients will be enrolled at each dose level The dose is based on the number of CD.30 CAR-EBVT-expressing cells administered. The total number of dose levels evaluated will depend upon toxicities experienced. Dose level cohorts will be numbered sequentially. * Dose Level 1: 4 × 10\^7 C7R.CD30.CAR-EBVST cells * Dose Level 2: 1 × 10\^8 C7R.CD30.CAR-EBVST cells * Dose Level 3: 4 × 10\^8 C7R.CD30.CAR-EBVST cells * Dose Level 4: 8 × 10\^8 C7R.CD30.CAR-EBVST cells

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+

Findings from Research

The study demonstrated that modifying Epstein-Barr virus-specific T-cells (EBVSTs) with a constitutively active IL7 receptor (C7R) significantly enhances their expansion and anti-tumor activity, showing promise for treating EBV-associated malignancies.
C7R-EBVSTs exhibited improved lymphoma control in a mouse model compared to unmodified T-cells, leading to the initiation of a clinical trial for patients with refractory or relapsed EBV-positive lymphoma.
Constitutive Interleukin-7 Cytokine Signaling Enhances the Persistence of Epstein-Barr Virus-Specific T-Cells.Sharma, S., Sauer, T., Omer, BA., et al.[2023]
CAR T-cell therapy is becoming a groundbreaking treatment for aggressive non-Hodgkin B-cell lymphoma, showing promise in improving patient outcomes.
The review discusses not only the efficacy of CAR T-cell therapy but also highlights the potential short- and long-term toxicities associated with the treatment, emphasizing the need for careful monitoring.
Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma.Hamilton, MP., Miklos, DB.[2023]
In a study involving 41 heavily pretreated patients with relapsed or refractory Hodgkin lymphoma, CD30-targeted CAR T-cell therapy demonstrated a high overall response rate of 72%, with 59% achieving complete responses after fludarabine-based lymphodepletion.
The therapy showed a favorable safety profile, with most adverse events being grade 3 or higher hematologic issues and only mild cytokine release syndrome observed, indicating that CAR T-cell therapy can be safely extended to treat Hodgkin lymphoma.
Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma.Ramos, CA., Grover, NS., Beaven, AW., et al.[2022]

References

Constitutive Interleukin-7 Cytokine Signaling Enhances the Persistence of Epstein-Barr Virus-Specific T-Cells. [2023]
Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. [2023]
Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. [2022]
Case of Myocarditis After Chimeric Antigen Receptor T Cells With Intracardiac Lymphoma. [2023]
CARs and cancers: questions and answers. [2021]
Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma. [2022]
Economic Burden of Neurologic Toxicities Associated with Treatment of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma in the United States. [2022]
CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin's Lymphoma. [2022]
Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis. [2019]
Anti-PD-1 Therapy Enhances the Efficacy of CD30-Directed Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed/Refractory CD30+ Lymphoma. [2022]
11.United Statespubmed.ncbi.nlm.nih.gov
Constant attack on T cell lymphomas. [2018]
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