CAR T-Cell Therapy + Ipilimumab for Non-Hodgkin's Lymphoma

(CRETI-NH Trial)

Recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Tumor vaccines

Disqualifiers: Pregnant, Lactating, Murine hypersensitivity, others

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

14 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not be currently receiving any investigational agents or have received any tumor vaccines within the previous six weeks.

What data supports the effectiveness of the treatment CAR T-Cell Therapy + Ipilimumab for Non-Hodgkin's Lymphoma?

Research shows that CAR T-cell therapy, which uses modified immune cells to target cancer, has been effective in treating certain types of B-cell non-Hodgkin lymphoma, especially in cases where other treatments have failed. This suggests potential effectiveness for the combination treatment being studied. ^{1 2 3 4 5}

Is CAR T-Cell Therapy + Ipilimumab safe for humans?

CAR T-cell therapy, including CD19-specific versions, has been generally safe in humans, with some patients experiencing mild to moderate side effects like cytokine release syndrome (a reaction causing fever and flu-like symptoms) and neurotoxicity (nerve-related issues). Serious side effects are rare, and the treatment is usually well-tolerated when managed by trained healthcare teams. ^{6 7 8 9 10}

How is the CAR T-Cell Therapy + Ipilimumab treatment different from other treatments for non-Hodgkin's lymphoma?

This treatment is unique because it combines CAR T-cell therapy, which uses modified immune cells to target cancer cells, with Ipilimumab, an immune checkpoint inhibitor that helps the immune system attack cancer more effectively. This combination aims to enhance the immune response against non-Hodgkin's lymphoma, potentially offering a new option for patients with relapsed or refractory forms of the disease. ^{3 4 5 11 12}

What is the purpose of this trial?

Patients on this study have a type of lymph gland cancer called non-Hodgkin Lymphoma, Acute Lymphocytic Leukemia, or chronic Lymphocytic Leukemia (these diseases will be referred to as "Lymphoma" or "Leukemia"). Their Lymphoma or Leukemia has come back or has not gone away after treatment (including the best treatment known for these cancers). This research study is a gene transfer study using special immune cells. The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, hoping that they 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. T lymphocytes can kill tumor cells but there normally are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person. The antibody used in this study is called anti-CD19. It first came from mice that have developed immunity to human lymphoma. This antibody sticks to cancer cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and Leukemia. For this study anti-CD19 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. In the laboratory, investigators have also found that T cells work better if they also put a protein that stimulates T cells called CD28. Investigators hope that adding the CD28 might also make the cells last for a longer time in the body. These CD19 chimeric receptor T cells with C28 T cells are investigational products not approved by the Food and Drug Administration. The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to see how the T cell with this sort of chimeric receptor lasts, to learn what the side effects are and to see whether this therapy might help people with lymphoma or leukemia.

Research Team

Carlos Ramos, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for people with certain types of blood cancers like non-Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, or Chronic Lymphocytic Leukemia that have returned or persisted despite treatment. Participants need to have a specific type of T-cell in their blood, be recovered from previous treatments, and meet certain health criteria including organ function and blood counts. Pregnant individuals or those with allergies to mouse proteins cannot join.

Inclusion Criteria

Bilirubin less than 3 times the upper limit of normal

I have recovered from side effects of my previous cancer treatments.

ANC greater than 500, HgB greater than 8.0

Exclusion Criteria

My tumor is located where it could block my airway if it grows.

You are pregnant or breastfeeding.

You have had allergic reactions to products that contain proteins from mice.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an injection of CD19 CD28 chimeric receptor-T cells, followed by potential additional doses if clinical benefit is observed

6 weeks

1 visit for initial infusion, potential additional visits for up to 3 extra doses

Follow-up

Participants are monitored for safety and effectiveness after treatment, with long-term follow-up for gene transfer side effects

15 years

Regular follow-up visits, with potential remote contact

Treatment Details

Interventions

• CD19CAR-28-zeta T cells

Trial Overview The study tests genetically modified T-cells combined with an antibody called anti-CD19 to fight cancer. These special cells are designed to better recognize and kill cancer cells by targeting CD19 on their surface. The trial aims to determine the highest safe dose, understand side effects, how long the T-cells last in the body, and if they're effective against lymphoma or leukemia.

Participant Groups

Group I: CD19CAR-28-zeta T cells Experimental Treatment 2 Interventions

Three dose levels of CTLs will be evaluated. Each patient will receive one injection according to their assigned dose over 1-10 minutes IV. \*At the discretion of the attending physician, if after a 4 to 6-week evaluation period the patient has had apparent clinical benefit (as determined by symptoms, physical exam or radiological studies); repeat infusions separated by 4 to 6 weeks (up to a maximum of 3 extra doses) of modified T cells at the same dose level or below the patient's original dose can be administered.

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Findings from Research

A patient with primary mediastinal large B-cell lymphoma achieved a complete metabolic response after receiving pembrolizumab following relapse 3.5 months post-CD19-directed CAR T-cell therapy, indicating the potential efficacy of immune checkpoint inhibitors in this setting.

Despite achieving remission, treatment with pembrolizumab was stopped after six cycles due to pneumonitis, highlighting the importance of monitoring for side effects while using immune checkpoint inhibitors after CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced Remission After Failure of Axicabtagene Ciloleucel: Case Report and Literature Review. Dimou, M., Bitsani, A., Bethge, W., et al.[2022]

CD19-directed CAR T-cell therapy has significantly transformed the treatment approach for aggressive B-cell non-Hodgkin lymphoma, offering new hope for patients.

There are currently three commercially available CAR T-cell therapies targeting CD19, indicating a growing acceptance and application of this innovative immunotherapy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. Gideon, J.[2023]

The novel CD19-PD-1/CD28 chimeric antigen receptor (CAR) T-cell therapy showed improved T-cell proliferation and effectiveness in killing PD-L1+ B-cell lymphoma cells, demonstrating enhanced efficacy compared to standard CD19 CAR T cells.

In a phase Ib study involving 17 adult patients with refractory or relapsed B-cell lymphoma, 58.8% of patients achieved an objective response, with 41.2% reaching complete remission, and the treatment was well-tolerated with no severe side effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-specific CAR T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor are Effective in Patients with PD-L1-positive B-Cell Lymphoma. Liu, H., Lei, W., Zhang, C., et al.[2022]

Adoptive cellular therapy using CAR-modified T cells targeting CD19 has shown significant clinical efficacy in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in both children and adults, with some patients also benefiting from treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma (B-NHL).

Current research is expanding the use of CAR T-cell therapies to other cancers, including multiple myeloma and solid tumors, while also addressing challenges such as severe cytokine release syndrome and neurologic toxicities associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. Geyer, MB., Brentjens, RJ.[2022]

Anti-CD19 CAR T-cell therapy has demonstrated significant clinical activity in treating B-cell non-Hodgkin lymphoma (NHL), with objective response rates ranging from 50-83% for relapsed diffuse large B-cell lymphoma (DLBCL), 83-93% for follicular lymphoma (FL), and 93% for mantle cell lymphoma (MCL).

This therapy represents a promising treatment option for patients with poor-risk refractory B-cell NHLs, highlighting its potential efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor T-cell therapy in B-cell lymphomas: current status and future directions. Chavez, JC., Yassine, F., Sandoval-Sus, J., et al.[2022]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

Adoptive cellular immunotherapy using anti-CD19 CAR-T cells has significantly improved treatment outcomes for patients with relapsed or refractory B cell lymphomas, leading to durable remissions, with two products already FDA-approved and a third in large clinical trials.

Despite their effectiveness, CAR-T cell therapies can cause serious side effects like infections and cytokine release syndrome, highlighting the need for better understanding of these toxicities and strategies to mitigate them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. Kallam, A., Vose, JM.[2020]

CD19-specific CAR T cell therapies are effective for treating difficult-to-treat blood cancers, but they can cause significant cardiovascular toxicity, including issues like tachycardia, arrhythmias, and left ventricular dysfunction.

There is a need for more research to better understand these cardiovascular risks and to develop a cardiac surveillance protocol for patients undergoing CAR T cell therapy, ensuring safer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Therapy-Related Cardiovascular Outcomes and Management: Systemic Disease or Direct Cardiotoxicity? Ghosh, AK., Chen, DH., Guha, A., et al.[2021]

CAR T cell therapies have shown high response rates in treating relapsed and refractory large cell lymphomas, with some patients experiencing long-lasting benefits.

The review emphasizes the importance of patient selection and the need for strategies to prevent relapse, as well as ongoing research into new CAR T cell therapies and their mechanisms of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dawn of Chimeric Antigen Receptor T Cell Therapy in Non-Hodgkin Lymphoma. Perica, K., Palomba, L., Brentjens, RJ.[2021]

In a phase I study involving 10 patients with refractory B-cell non-Hodgkin's lymphoma, the anti-CD19 CAR T cell therapy JWCAR029 achieved a remarkable overall response rate of 100%, with 66.7% of evaluable patients reaching complete remission.

While JWCAR029 was effective, it was associated with significant adverse events, including 100% incidence of neutropenia and grade 1 cytokine release syndrome in all patients, highlighting the importance of monitoring for side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Tumor Microenvironment Influence in a Dose-Escalation Study of Anti-CD19 Chimeric Antigen Receptor T Cells in Refractory B-Cell Non-Hodgkin's Lymphoma. Yan, ZX., Li, L., Wang, W., et al.[2020]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Pembrolizumab-induced Remission After Failure of Axicabtagene Ciloleucel: Case Report and Literature Review. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

CD19-specific CAR T Cells that Express a PD-1/CD28 Chimeric Switch-Receptor are Effective in Patients with PD-L1-positive B-Cell Lymphoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor T-cell therapy in B-cell lymphomas: current status and future directions. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. [2020]

9. England pubmed.ncbi.nlm.nih.gov

CAR T-cell immunotherapy of B-cell malignancy: the story so far. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

CAR T Cell Therapy-Related Cardiovascular Outcomes and Management: Systemic Disease or Direct Cardiotoxicity? [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Dawn of Chimeric Antigen Receptor T Cell Therapy in Non-Hodgkin Lymphoma. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Clinical Efficacy and Tumor Microenvironment Influence in a Dose-Escalation Study of Anti-CD19 Chimeric Antigen Receptor T Cells in Refractory B-Cell Non-Hodgkin's Lymphoma. [2020]