CAR-T Cell Therapy for Non-Hodgkin Lymphoma

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Benjamin Tomlinson

Must not be taking: Immunosuppressive medications

Disqualifiers: CNS involvement, Active malignancy, HIV, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to combat non-Hodgkin lymphoma using CAR-T cell therapy. CAR-T cells are special immune cells taken from the body, modified in a lab to better target cancer, and then returned to the body. The trial aims to determine if this treatment can effectively treat cancer and identify any possible side effects. Suitable candidates have non-Hodgkin lymphoma that hasn't improved with at least two treatments and have CD19-positive lymphoma. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medication for an autoimmune disease, you must not have taken it within the last 6 months to be eligible.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CAR-T cell therapy is generally safe for treating non-Hodgkin lymphoma. Studies indicate that about 5% to 10% of patients might experience severe, potentially life-threatening side effects, though this is relatively uncommon. Most patients tolerate the treatment well. Common side effects include flu-like symptoms, which are usually manageable and temporary.

Before receiving CAR-T cells, patients often take Cyclophosphamide and Fludarabine to prepare their bodies. These drugs can cause side effects like nausea and tiredness, but these are usually temporary and treatable.

Overall, CAR-T cell therapy appears promising in terms of safety, with most side effects being manageable. It is important for patients to discuss potential risks and benefits with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Non-Hodgkin Lymphoma, which often include chemotherapy and radiation, CAR-T Cell Therapy offers a unique approach by harnessing the body's immune system to fight the cancer. This therapy involves engineering a patient’s own T-cells to better recognize and attack cancer cells, providing a targeted and personalized treatment option. Researchers are excited about CAR-T Cells because they have the potential to lead to longer-lasting remissions and are particularly promising for patients who have not responded well to conventional treatments.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin Lymphoma?

Research has shown that CAR-T cell therapy, administered to participants in this trial following a lymphodepletive regimen with Cyclophosphamide and Fludarabine, has improved health outcomes for patients with Non-Hodgkin Lymphoma (NHL). Studies indicate that this treatment can extend patients' lives and delay disease progression. In everyday situations, patients have reported feeling better after receiving CAR-T cells. This treatment modifies a type of white blood cell, called T cells, to better identify and combat cancer cells. Overall, evidence supports CAR-T cell therapy as a promising treatment for NHL. ^{3 5 6 7 8}

Who Is on the Research Team?

Benjamin Tomlinson, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with Non-Hodgkin's Lymphoma that has returned or didn't respond after two treatments. They must have a certain level of blood cells, CD19 positive lymphoma, decent physical function, and normal organ function. People can't join if they've had recent transplants, CNS issues, other active cancers, uncontrolled illnesses, are pregnant/breastfeeding, have hepatitis B/C or HIV infection.

Inclusion Criteria

Total bilirubin ≤ 1.5 times the institutional upper limit of normal

Aspartate transaminase (AST or SGOT) ≤ 3 X institutional upper limit of normal

Absolute neutrophil count (ANC) > 1,000/uL

Exclusion Criteria

I have an active cancer other than non-dangerous skin cancer or early-stage cancers that haven't spread.

I do not have any severe illnesses that would stop me from following the study's requirements.

I do not have severe brain conditions like epilepsy, stroke, or Parkinson's.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive a lymphodepletive regimen consisting of Cyclophosphamide and Fludarabine

6 days

Daily visits for infusion

CAR-T Cell Infusion

Infusion of Chimeric Antigen Receptor T-cells (CAR-T) on day 0

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• CAR-T Cells
• Cyclophosphamide
• Fludarabine

Trial Overview The study tests a new immunotherapy using modified T cells (CAR-T Cells) combined with chemotherapy drugs Cyclophosphamide and Fludarabine to target cancer in those whose Non-Hodgkin's Lymphoma hasn't responded to standard treatments.

How Is the Trial Designed?

Group I: Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells Experimental Treatment 3 Interventions

Lymphodepletive regimen, consisting of Cyclophosphamide 60mg/kg IV on day -6 and Fludarabine 25mg/m2 IV on days -5 to -3. Followed by infusion of Chimeric antigen receptor T-cells (CAR-T) on day 0

Who Is Running the Clinical Trial?

Benjamin Tomlinson

Lead Sponsor

Trials

4

Recruited

110+

Published Research Related to This Trial

Cellular therapies, including CAR T cells and allogeneic stem cell transplantation, have shown significant effectiveness in treating aggressive non-Hodgkin lymphomas, particularly in patients with poor prognoses.

The article discusses the clinical approach to selecting patients for CD19-directed CAR T cell therapy, emphasizing its growing importance in lymphoma management and the potential of newer cell therapies to enhance immunotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy with cells. Chong, EA., Porter, DL.[2023]

CAR-T cell therapy has shown great promise in treating hematological cancers, with two Anti-CD19 CAR-T therapies already approved for CD19-positive leukemia and lymphoma.

However, the therapy can cause serious side effects like cytokine release syndrome and on-target off-tumor toxicity, leading to some patients discontinuing treatment; researchers are exploring various safety strategies to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. Yu, S., Yi, M., Qin, S., et al.[2020]

CAR-T cell therapy combined with anti-PD-1 immunotherapy shows promising efficacy in treating lymphoma, with an overall response rate of 65% based on an analysis of 57 patients from 5 clinical trials.

The most common adverse effect observed was fever, with a pooled incidence of 59%, indicating that while the therapy is effective, it does come with notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. Zhou, Y., Mu, W., Wang, C., 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

A 61-year-old male patient with intravascular large B-cell lymphoma and CNS involvement achieved complete remission after receiving CAR T-cell therapy following a conditioning regimen and autologous stem cell transplantation.

The treatment was associated with only mild side effects, specifically grade 1 cytokine release syndrome, and no serious adverse events like neurotoxicity or pseudoprogression, suggesting that CAR T-cell therapy can be safely administered to patients with CNS involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report. Yagi, Y., Kanemasa, Y., Ohigashi, A., et al.[2022]

CAR T cell therapy is effective in treating B cell malignancies like acute lymphoblastic leukemia and non-Hodgkin lymphomas, but it can also cause serious side effects, including multi-organ failure.

Early recognition and management of side effects such as cytokine release syndrome and neurotoxicity are crucial for healthcare staff to ensure patient safety during CAR T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. Yáñez, L., Alarcón, A., Sánchez-Escamilla, M., et al.[2021]

CAR T cell therapy has shown great promise in treating certain blood cancers, but it can lead to serious side effects, including potentially fatal toxicities from cytokine release and off-target effects that harm healthy tissues.

Recent strategies to improve safety include modifying CAR structures and incorporating elements like switch molecules and suicide genes to reduce the toxic effects of CAR T cells on normal tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for modifying the chimeric antigen receptor (CAR) to improve safety and reduce toxicity in CAR T cell therapy for cancer. Sayadmanesh, A., Yekehfallah, V., Valizadeh, A., et al.[2023]

CAR-T cell therapy has shown remarkable success in treating B-cell malignancies, but researchers are focused on improving its safety and effectiveness due to risks like cytokine release syndrome and off-target effects.

Innovative safety strategies, such as ON- and OFF-switch CARs and multi-antigen-targeting CAR-T cells, are being developed to enhance the persistence and reduce adverse events associated with CAR-T therapy, paving the way for a new generation of treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering Next-Generation CAR-T Cells for Better Toxicity Management. Andrea, AE., Chiron, A., Bessoles, S., et al.[2023]

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]

CAR T cell therapy has shown significantly better response rates in patients with relapsed non-Hodgkin lymphoma compared to traditional salvage chemotherapy, indicating its efficacy in this challenging setting.

While CAR T therapy can lead to side effects like cytokine release syndrome and neurological events, most patients recover from these effects, suggesting a manageable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience of CAR T cell therapy in lymphomas. Oluwole, OO.[2022]

Citations

1. astctjournal.org astctjournal.org/article/S2666-6367(25)01462-9/fulltext

Patient-Reported Outcomes of CAR T-Cell Therapy in Non- ... This study demonstrates that CAR T-cell therapy improves overall HRQoL in NHL patients across different countries in the real-world setting.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10972674/

Chimeric Antigen Receptor (CAR)-T Cell Therapy for Non- ... Overall, CAR-T cell therapies have improved clinical outcomes in NHL patients and generated optimism around their future applications. Keywords: ...

3. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00070-7/fulltext

Treatment of non-Hodgkin lymphoma with point-of-care ... After a median duration of follow up from CAR T-cell infusion of 24.5 months (IQR 17–32) among the event-free, 7 patients relapsed and 10 died.

4. nature.com nature.com/articles/s41571-023-00754-1

Long-term outcomes following CAR T cell therapy These CAR T cells have also generated CR rates of 71–81% in multicentre clinical trials involving patients with R/R B cell acute lymphoblastic ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124093777

Efficacy and Safety of CAR T-Cell Therapy in Non-Hodgkin ... A pooled analysis of the outcomes found that CAR-TCT significantly increased both the OS and the PFS of NHL patients compared to the standard of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38582666/

Safety and Toxicity Profiles of CAR T Cell Therapy in Non- ... Background: The application of CD19-directed chimeric antigen receptor T (CAR T) cell therapy has improved outcomes for thousands of patients with non-Hodgkin B ...

7. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2830583

Adverse Events After CAR T-Cell Therapy in B-Cell Non- ... The risk of nonrelapse mortality (NRM) after CAR T-cell therapy among patients with relapsed or refractory LBCL is approximately 5% to 10%, ...

8. nature.com nature.com/articles/s41409-025-02691-2

Safety and efficacy of autologous humanized CD19 CAR-T ... Limited research has evaluated humanized CD19-targeted CAR-T cells (hCART19) in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).