UF-KURE19 CAR-T Cells for Non-Hodgkin Lymphoma

Recruiting at 1 trial location

Overseen By Paolo F. Caimi

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Changchun Deng, MD

Must not be taking: Immunosuppressants, others

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: Unknown

Duration: 1 day

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of a new treatment using UF-KURE19 CAR-T cells for individuals with Non-Hodgkin Lymphoma. The treatment modifies a patient's own immune cells to enhance their ability to combat cancer. Candidates who have undergone at least two unsuccessful chemotherapy treatments or are ineligible for a stem cell transplant might be suitable participants. As a Phase 1 trial, the research focuses on understanding how the treatment functions in humans, providing participants 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 whether you need to stop taking your current medications. However, it mentions that you must wait at least 28 days after any investigational treatments before participating, and you should not be on systemic immunosuppressive medications other than low-dose steroids within the last 6 months.

Is there any evidence suggesting that UF-KURE19 CAR-T cells are likely to be safe for humans?

Research has shown that UF-KURE19 CAR-T cells are promising in terms of safety. Studies indicate that this treatment for Non-Hodgkin Lymphoma is generally well-tolerated, with most people experiencing few harmful side effects. It has demonstrated low toxicity levels while effectively treating patients.

Although testing remains in the early stages, current data suggests that UF-KURE19 CAR-T cells could be a safe option for those considering this trial. However, always consult a healthcare provider about potential risks before joining any clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about UF-KURE19 CAR-T cells for treating Non-Hodgkin Lymphoma because of their innovative mechanism. Unlike traditional treatments like chemotherapy or radiation, which target all rapidly dividing cells, CAR-T cell therapy harnesses the body's immune system to specifically target and destroy cancer cells. This precision not only promises to improve effectiveness but also potentially reduces the side effects associated with broader treatments. Additionally, UF-KURE19 CAR-T cells are customized to each patient, offering a personalized approach that could lead to better outcomes.

What evidence suggests that UF-KURE19 CAR-T cells might be an effective treatment for Non-Hodgkin Lymphoma?

Research has shown that UF-KURE19 CAR-T cells, which participants in this trial will receive, effectively treat non-Hodgkin lymphoma. In previous studies, this treatment achieved an 80% complete response rate, meaning most patients experienced complete cancer remission. The treatment is also known for having fewer harmful side effects. UF-KURE19 is produced quickly, making it more accessible than other similar treatments. This therapy also has a good safety record, with fewer cases of serious side effects like cytokine release syndrome (CRS) and nerve problems, which are common with other treatments. Overall, evidence suggests UF-KURE19 could be a promising option for patients. ^{1 3 5 6 7}

Who Is on the Research Team?

Changchun Deng, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults with CD19 positive, non-Hodgkin lymphoma that's come back after at least two treatments or hasn't responded to chemo. They must be in relatively good health, not pregnant, willing to use effective birth control, and have no major organ dysfunction or other serious medical conditions.

Inclusion Criteria

Subjects must have a CD3% ≥ 40% of total PBMCs confirmed through flow cytometry.

At least one measurable lesion according to Lugano Revised Response Criteria for Malignant Lymphoma.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I have severe heart failure.

I have a significant brain condition like epilepsy, stroke, or Parkinson's.

My blood test shows cancerous B cells.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Therapy

Participants receive lymphodepleting therapy with Fludarabine and Cyclophosphamide

3 days

In-patient treatment

Treatment

Participants receive UF-KURE19 CAR-T cell infusion

1 day

In-patient treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• UF-KURE19 CAR-T cells

Trial Overview The trial is testing UF-KURE19 CAR-T cells made from the patient's own T cells modified by a deactivated virus to fight cancer. It also uses Cyclophosphamide and Fludarabine before reinfusing these engineered cells. The process is quicker than other CAR-T therapies.

How Is the Trial Designed?

Group I: UF-KURE19 CAR-T cell infusion Experimental Treatment 3 Interventions

The safety and manufacturing feasibility of UF-KURE19 will be determined with up to 10 patients being enrolled. Lymphodepleting therapy will begin on Days -4 to -2 with each weight category of participants receiving 30mg/m2/IV of Fludarabine and 500mg/m2/IV of Cyclophosphamide regardless of the level of UF-KURE19 CAR-T cell dosing. Dosing: Participants greater than or equal to 50 kg: * Level -1: 10 x 10\^6 UF-KURE19 CAR-T Cell Dose (CAR positive cells) * Level 1 : 17.5 x 10\^6 UF-KURE19 CAR-T Cell Dose Participants less than 50 kg: * Level -1: 6.5 x 10\^6 UF-KURE19 CAR-T Cell Dose * Level 1: 11.5 x 10\^6 UF-KURE19 CAR-T Cell Dose

Who Is Running the Clinical Trial?

Changchun Deng, MD

Lead Sponsor

Trials

1

Recruited

20+

David Wald

Lead Sponsor

Trials

3

Recruited

40+

James Michael Martin

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

Anti-CD19 CAR T-cell therapy has shown remarkable efficacy in treating relapsed or refractory aggressive B-cell lymphomas, leading to durable remissions in patients who previously had no effective treatment options.

Three CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) are approved for use, each differing in their design, manufacturing processes, and safety profiles, highlighting the need for personalized approaches in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Abramson, JS.[2021]

Anti-CD19-directed CAR T cell therapy has shown significant efficacy in treating relapsed or refractory B-cell malignancies, leading to the approval of tisagenlecleucel (Kymriah) for B-ALL in 2018 and for aggressive B-cell lymphoma shortly thereafter.

The review highlights ongoing research into resistance mechanisms and the exploration of new target antigens, indicating a continued effort to improve treatment outcomes for patients with CD19 positive B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. Balke-Want, H., Borchmann, P.[2021]

Allogeneic anti-CD19 CAR T-cell therapy shows high efficacy in treating relapsed or refractory acute lymphoblastic leukemia (ALL), with an 80% complete remission rate and a 51% one-year overall survival rate among patients.

The therapy demonstrates a favorable safety profile, with a low graft-versus-host disease (GvHD) rate of 4% and a manageable cytokine release syndrome rate of 69%, indicating it is a viable treatment option for both ALL and non-Hodgkin lymphoma (NHL).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Donor-derived and off-the-shelf allogeneic anti-CD19 CAR T-cell therapy for R/R ALL and NHL: A systematic review and meta-analysis. Chen, S., Zhang, Y., Fang, C., et al.[2022]

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 targeting the CD19 antigen has significantly changed treatment for patients with relapsed or refractory B cell non-Hodgkin lymphoma, with two FDA-approved products available: axicabtagene ciloleucel and tisagenlecleucel.

The review highlights the clinical outcomes and toxicity profiles of these CAR-T therapies, indicating their effectiveness across major B cell NHL subtypes, while also discussing new CAR-T constructs currently being researched.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor modified T cell therapy in B cell non-Hodgkin lymphomas. Levin, A., Shah, NN.[2021]

In a study involving 1,926 subjects from 17 clinical trials, patients with acute lymphocytic leukemia (ALL) were found to have a higher risk of severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) compared to those with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM).

The use of CAR T cells produced with gammaretrovirus vectors containing CD28 sequences was linked to increased rates of sNTX, while administering cytokine-directed therapies and corticosteroids at lower toxicity grades was associated with reduced rates of sCRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. Foster, M., Negash, Y., Eberhardt, L., et al.[2022]

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]

Five anti-CD19 CAR T-cell therapies are FDA-approved for treating various lymphoid malignancies, including B-cell non-Hodgkin lymphoma and pediatric B-cell acute lymphoblastic leukemia, demonstrating their efficacy in these conditions.

Ongoing clinical trials are exploring the use of CAR T cells for other blood cancers like chronic lymphocytic leukemia and acute myeloid leukemia, indicating a broadening scope of CAR T-cell therapy beyond currently approved indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy in Hematologic Malignancies: Clinical Role, Toxicity, and Unanswered Questions. Gill, S., Brudno, JN.[2021]

A novel CAR T-cell therapy targeting CD79b has been developed, showing strong antitumor activity against B-cell lymphomas in both laboratory and animal models, including the ability to attack tumors that have relapsed after CD19-targeted therapies.

The CD79b CAR T cells demonstrated effective proliferation and cytotoxic activity without significant signs of exhaustion, supporting their potential for use in a phase 1 clinical trial for patients with relapsed or refractory B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cells to target CD79b in B-cell lymphomas. Chu, F., Cao, J., Liu, J., et al.[2023]

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 ZUMA-7 trial showed that axicabtagene ciloleucel (axi-cel) significantly improves overall survival and event-free survival compared to standard-of-care treatments for early-relapsed or refractory large B cell lymphoma, marking a major advancement in treatment options after nearly 30 years.

CAR T cell therapies, particularly axi-cel and lisocabtagene maraleucel (liso-cel), are proving effective as second-line treatments for elderly and transplant-ineligible patients, with potential for use as first-line therapies for high-risk large B cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving Role of CAR T Cell Therapy in First- and Second-Line Treatment of Large B Cell Lymphoma. Lionel, AC., Westin, J.[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]

In a phase IIa trial involving 11 patients with relapsed or refractory CD20+ B-cell lymphoma, the use of CAR-modified T cells (CART-20) resulted in an impressive overall response rate of 81.8%, with 6 complete remissions and 3 partial remissions, indicating strong efficacy.

The treatment was well-tolerated with no severe toxicity reported, and the median progression-free survival was over 6 months, suggesting that CART-20 is a promising option for patients with difficult-to-treat lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. Zhang, WY., Wang, Y., Guo, YL., et al.[2021]

CD19-directed autologous CAR T cell therapy has shown remarkable effectiveness in treating relapsed and refractory non-Hodgkin lymphoma (NHL), leading to significant response rates and prolonged remissions, which has resulted in FDA approval for four CAR T cell products from 2017 to 2021.

Due to its success, there is growing interest in using autologous CAR T cells earlier in treatment for large B cell lymphoma, highlighting the need for ongoing management of associated toxicities and the exploration of allogeneic CAR T options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Based Therapies in Lymphoma: A Review of Current Practice and Perspectives. Sheikh, S., Migliorini, D., Lang, N.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124028416

Phase I Study Results of UF-Kure19, a CAR-T Product ... Overall, UF-Kure19 demonstrated high efficacy and tolerability, with the potential to address current accessibility challenges and extend CAR-T ...

2. onclive.com onclive.com/view/uf-kure19-car-t-cell-therapy-demonstrates-high-cr-rates-low-toxicity-in-r-r-nhl

UF-Kure19 CAR-T Cell Therapy Demonstrates High CR ... UF-Kure19 achieved an 80% complete response rate in relapsed/refractory non-Hodgkin lymphoma patients, with low toxicity levels. The therapy's ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05400109

NCT05400109 | Evaluate the Safety of UF-KURE19 Cells ... The investigators are evaluating UF-KURE19 because it uses a process that is shorter than other approved CAR-T cells. While the shorter manufacture time can be ...

4. reporter.nih.gov reporter.nih.gov/project-details/11184038

Ultra-fast manufactured CAR-T therapy This trial involved the treatment of 10 patients with relapsed/refractory non-hodgkin's lymphoma and led to an extremely promising safety and efficacy profile ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324925001021

DEVELOPMENT AND CLINICAL VALIDATION OF A LESS ... UF-Kure19 demonstrated a promising safety profile with no reported DLTs. The incidence of CRS and Neurotoxicity were markedly lower than reported for FDA ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/94/530351/Phase-I-Study-Results-of-UF-Kure19-a-CAR-T-Product

Phase I Study Results of UF-Kure19, a CAR-T Product ... CD19 CAR-T therapy has markedly improved outcomes for Non-Hodgkin's Lymphoma (NHL) patients, yet its availability is critically limited.

7. cancer.gov cancer.gov/clinicaltrials/NCI-2022-08980

UF-KURE19 CAR-T Cells for Treatment of Non-Hodgkin ... This phase I/Ib trial tests the safety, side effects, and best dose of UF-KURE19 CAR-T cells in treating patients with non-Hodgkin lymphoma. CAR T-cell ...