CAR-T Cell Therapy for Lymphoma

(CABAL2 Trial)

Recruiting at 1 trial location

Overseen By Premal Lulla, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Systemic corticosteroids

Disqualifiers: Pregnant, Cardiac disease, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for certain types of lymphoma, a cancer affecting the lymphatic system. The treatment uses special cells, called C7R.CD30.CAR-EBVST cells, modified to fight cancer more effectively by adding a molecule called C7R. Researchers aim to determine if this treatment is safe and effective for patients whose lymphoma has returned or hasn't responded to previous treatments. Patients with Hodgkin lymphoma, CD30+ aggressive B-cell lymphoma, or specific T-cell lymphomas with CD30-positive tumors might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering patients the opportunity to be among the first to receive this innovative therapy.

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.

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

Research has shown that CD30.CAR T cells, specially modified to target certain lymphoma cells, hold promise. In earlier studies, researchers made these cells from a patient's own blood and reintroduced them to fight cancer. Another study used donor cells (allogeneic), which also yielded promising results without safety concerns.

Specifically, CD30.CAR T cells have been tested in patients with CD30+ lymphomas. Some patients experienced side effects like rashes and low blood cell counts, though not everyone did. In some cases, the treatment was well tolerated, offering a potential new way to combat lymphoma.

In this trial, researchers add a new molecule called C7R to the CD30.CAR T cells to enhance their effectiveness. If severe side effects occur, a safety switch using the drug rimiducid can be activated to stop them. Rimiducid has been used in patients before without causing serious side effects.

Overall, while potential side effects exist, previous studies have shown the treatment to be safe. Participants will be closely monitored to manage any adverse effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for lymphoma, which typically involves chemotherapy, radiation, and sometimes stem cell transplants, C7R.CD30.CAR-EBVST cells offer a targeted approach. This treatment is unique because it leverages CAR-T cell therapy, where a patient's own immune cells are engineered to better recognize and attack cancer cells. Researchers are excited because this method specifically targets the CD30 protein on lymphoma cells, potentially offering a more precise treatment with fewer side effects compared to traditional therapies. This precision could lead to improved outcomes and a better quality of life for patients.

What evidence suggests that C7R.CD30.CAR-EBVST cells might be an effective treatment for lymphoma?

Research has shown that CD30.CAR T cells, specially modified to attack cancer cells, have potential in treating certain types of lymphoma. These cells are created from a patient's own blood and then reintroduced to help fight the cancer, showing positive results in patients. Another method uses cells from healthy donors, which are readily available and have shown promising results in ongoing studies without safety issues. This trial involves the investigational treatment of C7R.CD30.CAR-EBVST cells, which incorporate a molecule called C7R. Lab tests have shown that this molecule strengthens and prolongs anticancer effects. This approach offers a promising treatment option for patients whose lymphoma has returned or not responded to previous treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Premal Lulla, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Treatment Phase Experimental Treatment 1 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

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 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. Hamilton, MP., Miklos, DB.[2023]

CAR-T therapy is an innovative treatment that modifies T cells to target and attack cancer cells, such as those found in large B cell lymphoma.

In this case, a patient treated with CAR-T therapy for lymphoma developed myocarditis, highlighting a potential safety concern associated with this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case of Myocarditis After Chimeric Antigen Receptor T Cells With Intracardiac Lymphoma. Lee, DH., Jain, M., Lazaryan, A., et al.[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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. Ramos, CA., Grover, NS., Beaven, AW., et al.[2022]

The study reports on three patients with relapsed B-cell lymphomas who were treated with autologous T cells modified to express a CD20-targeted chimeric antigen receptor (CAR), showing promising clinical efficacy.

The treatment demonstrated a favorable safety profile, indicating that genetically modified T cells can be a viable option for patients with relapsed B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CARs and cancers: questions and answers. Brentjens, RJ.[2021]

In a study of 11,098 adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), 2.7% experienced severe neurologic adverse events (AEs) within 30 days of treatment, with a significant portion (36.4%) of those receiving CAR T-cell therapy affected.

Patients with neurologic AEs incurred an average of $71,982 higher healthcare costs, with CAR T-cell therapy users facing the highest costs, highlighting the financial burden associated with these severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic Burden of Neurologic Toxicities Associated with Treatment of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma in the United States. Broder, MS., Ma, Q., Yan, T., et al.[2022]

In a multi-center phase II clinical trial involving 12 patients with relapsed/refractory CD30+ lymphoma, the combination of anti-CD30 CAR-T therapy and PD-1 inhibitors resulted in a high overall response rate of 91.7%, with 50% of patients achieving complete remission.

The treatment demonstrated minimal toxicity, with only 4 patients experiencing cytokine release syndrome, and no cases of CAR-T-related encephalopathy syndrome, indicating a favorable safety profile alongside its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD-1 Therapy Enhances the Efficacy of CD30-Directed Chimeric Antigen Receptor T Cell Therapy in Patients With Relapsed/Refractory CD30+ Lymphoma. Sang, W., Wang, X., Geng, H., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Constitutive Interleukin-7 Cytokine Signaling Enhances the Persistence of Epstein-Barr Virus-Specific T-Cells. Sharma, S., Sauer, T., Omer, BA., et al.[2023]

In a study of 38 classical Hodgkin's Lymphoma (cHL) specimens, only 5.2% of Reed-Sternberg cells expressed both CD19 and CD30, indicating a limited population eligible for combined CAR T-cell therapy.

A patient treated with low doses of anti-CD19 and CD30 CAR T-cells did not experience severe adverse events and achieved long-term progression-free survival, suggesting that this approach may be safe and effective for high-risk relapsing/refractory cHL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin's Lymphoma. Xue, Y., Lai, X., Li, R., et al.[2022]

CAR-T cell therapy shows promise in treating relapsed or refractory malignancies, particularly in hematological cancers like acute B-cell lymphoblastic leukemia and B-cell lymphomas, with ongoing research into its application for solid tumors.

This systematic review aims to comprehensively assess the safety and efficacy of CAR-T cell therapy by analyzing various studies, focusing on outcomes such as complete response rates and adverse events, to better understand its potential risks and benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Grigor, EJM., Fergusson, DA., Haggar, F., et al.[2019]

In a study of 133 patients with relapsed or refractory lymphomas receiving CAR-T-cell therapy, severe cytopenias (neutropenia, anemia, and thrombocytopenia) were common, occurring in 71%, 30%, and 41% of patients, respectively, particularly in the early phase after treatment.

Severe cytopenias were linked to higher rates of infections and poorer survival outcomes, suggesting that better patient selection and management of cytokine release syndrome (CRS) could reduce these adverse effects and improve overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytopenia after chimeric antigen receptor T cell immunotherapy in relapsed or refractory lymphoma. Zhou, J., Zhang, Y., Shan, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7655020/

Anti-CD30 CAR-T Cell Therapy in Relapsed and ... We found that targeting CD30 in HL with CAR-Ts can be similarly effective. Although CD30.CAR-Ts showed modest activity in HL when infused without ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06176690?cond=Anaplastic%20large%20cell%20lymphoma%20OR%20%22ALCL%22%20OR%20%22%20cd30%20positive%20anaplastic%20large%20cell%20lymphoma%22%20OR%20%22%20Ki-1%20lymphoma%22%20OR%20%22%20Ki-1%20positive%20anaplastic%20large%20cell%20lymphoma%22%20OR%20%22%20Ki-1%20%20ALCL%22%20OR%20%22%20Ki-1%20%20anaplastic%20large%20cell%20lymphoma%22%20OR%20%22%20primary%20systemic%20ALCL%22%20OR%20%22%20sACL%22&aggFilters=status:not%20rec&viewType=Table&rank=10

Constitutive IL7R (C7R) Modified Banked Allogeneic CD30 ... 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 ...

3. cell.com cell.com/molecular-therapy-family/oncology/fulltext/S2950-3299(24)00056-0

Rejection resistant CD30.CAR-modified Epstein-Barr virus- ... In conclusion, we show that CD30.CAR EBVSTs have the potential to be an effective OTS therapy against CD30+ tumors and, if successful, could ...

4. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/412/491233/CD30-CAR-Modified-Epstein-Barr-Virus-Specific-T

CD30.CAR-Modified Epstein-Barr Virus-Specific T Cells ... CAR-modified Epstein-Barr virus-specific T cells (CD30.CAR EBVSTs) provide a safe and effective off-the-shelf therapy for patients with CD30-positive lymphoma.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X25000157

Immunotherapy for paediatric diffuse large B-cell lymphoma In a Phase I/II trial of adult R/R B-NHL patients, epcoritamab monotherapy showed a 68 % response rate and a 45 % CR rate, regardless of prior CAR-T exposure [ ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10874855/

Transient responses and significant toxicities of anti-CD30 ... Anti-CD30 CAR T cells had low efficacy in patients with CD30-expressing lymphoma. Rashes and prolonged cytopenias were frequent and severe in some cases.

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3465/529134/Safety-and-Efficacy-of-CD30-Directed-Chimeric

Safety and Efficacy of CD30-Directed Chimeric Antigen ... The estimated 2-year overall survival (OS) was 100% and the median OS for all cHL patients has not been reached. Expansion and/or persistence of ...