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

(CRETI-NH Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for certain blood cancers, such as non-Hodgkin's lymphoma and leukemia, that have not responded well to other treatments. It employs a special cell therapy where T cells (a type of immune cell) are modified in the lab to better target and kill cancer cells. The trial aims to determine the safest and most effective dose of these modified T cells, called CD19CAR-28-zeta T cells, and assess their longevity in the body. Suitable candidates for this trial have recurring B cell lymphoma or leukemia that has not improved with standard treatments, or they have a new diagnosis and cannot complete regular therapy. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

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

Research has shown that CD19-targeted CAR T cells offer promise for treating B cell cancers like non-Hodgkin lymphoma. Studies have found that this treatment can lead to long-lasting cancer control with only minor long-term side effects. It appears to benefit many patients who did not improve with other treatments.

Despite positive results, some patients experienced cancer recurrence or serious side effects. These side effects can include fever or trouble breathing, which are usually manageable but can be serious.

The CD19CAR-28-zeta T cells used in this trial are still under investigation for safety, as they are not yet FDA-approved for any condition. This trial represents an early step in determining the safest dose and understanding potential side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Non-Hodgkin's Lymphoma, which often include chemotherapy and radiation, CD19CAR-28-zeta T cells represent a cutting-edge approach by employing a patient's own immune cells to fight cancer. This treatment works by modifying T cells to target and destroy cancerous cells that express the CD19 protein, offering a more personalized and potentially more effective therapy. Researchers are excited because this method could lead to longer-lasting remissions with fewer side effects compared to traditional therapies.

What evidence suggests that this treatment might be an effective treatment for lymphoma or leukemia?

Research has shown that CAR T-cell therapies, such as CD19CAR-28-zeta T cells, hold promise for treating non-Hodgkin's lymphoma. In studies, 50% to 93% of patients with relapsed lymphoma experienced tumor reduction or remission after treatment. This therapy combines T cells, which are special blood cells that fight infections, with antibodies that specifically target cancer cells. This combination aims to enhance the immune system's ability to locate and destroy cancer cells. Although not yet approved, CD19 chimeric receptor T cells are under investigation for their potential benefits in treating lymphomas and leukemias. ^{2 3 6 7 8}

Who Is on the Research Team?

Carlos Ramos, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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

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

ANC greater than 500, HgB greater than 8.0

Bilirubin less than 3 times the upper limit of normal

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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