What is the mechanism of action of this treatment?

CAR-T cell therapy, a prominent treatment for Non-Hodgkin's Lymphoma (NHL), involves modifying a patient's T cells to express chimeric antigen receptors (CARs) that target specific cancer cell proteins. This modification is typically achieved using a lentivirus to integrate the CAR gene into the T cells. Upon reinfusion, these engineered T cells can specifically recognize and destroy cancer cells. This targeted approach is crucial for NHL patients as it provides a potential for long-term remission, particularly in relapsed or refractory cases where conventional treatments have not been effective.

What side effects are associated with this type of intervention?

CAR-T cell therapies for Non-Hodgkin's Lymphoma, such as UF-KURE19, commonly cause cytokine release syndrome (CRS) and neurotoxicity. CRS can lead to fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing. Neurotoxicity may present as confusion, difficulty speaking, seizures, or severe headaches. Additionally, there is an increased risk of infections due to the immunosuppressive effects of the treatment. These side effects are important factors to consider when determining the appropriateness of CAR-T cell therapies.

What prior FDA approvals exist?

The FDA has approved several CAR-T cell therapies for the treatment of relapsed or refractory Non-Hodgkin's Lymphoma. Notable examples include axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), both of which are CD19-directed CAR-T cell therapies. These treatments involve modifying a patient's T cells to target CD19, a protein found on the surface of B cells, including those in certain types of NHL. These therapies have shown high response rates in clinical trials and are available through specialized programs due to their potential for serious side effects, such as cytokine release syndrome and neurologic events.

What other types of research exist?

Promising novel alternatives to UF-KURE19 CAR-T cells for Non-Hodgkin's Lymphoma patients include: 1) Lisocabtagene Maraleucel (liso-cel), a CD19-directed CAR-T cell therapy, which has shown efficacy in the Transform Study for relapsed or refractory large B-cell lymphoma. 2) Axicabtagene Ciloleucel, another CD19-directed CAR-T cell therapy, used as second-line therapy for large B-cell lymphoma. 3) Tisagenlecleucel, also a CD19-directed CAR-T cell therapy, which has been evaluated as a second-line treatment for aggressive B-cell lymphoma. These therapies offer potential benefits and should be discussed with a healthcare provider.

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CAR T-cell Therapy

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

Phase 1

Waitlist Available

Led By Changchun Deng, MD, PhD

Research Sponsored by Changchun Deng, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

ECOG Performance status ≤ 2

Cardiac ejection fraction of ≥45%, and no evidence of pericardial effusion, as determined by an echocardiogram.

Must not have

New York Heart Association class IV congestive heart failure.

Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 weeks after culture of uf-kure19 car-t cells

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a cancer treatment where a patient's own immune cells are modified outside the body and then reintroduced to fight the cancer. The process uses a virus to change the cells, making them better at attacking cancer. This method is quicker than other similar treatments, but its safety is still being studied.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include reactions related to immune system activation such as fever and fatigue, possible damage to organs where T-cells attack healthy tissue (like inflammation), and typical chemotherapy-related issues like nausea or low blood counts.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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My heart pumps well and I don't have fluid around it.

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My lymphoma is CD19 positive and has not improved after at least 2 treatments.

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My kidneys are functioning well enough, based on a specific calculation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have severe heart failure.

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

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My blood test shows cancerous B cells.

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I do not have a second active cancer except for non-dangerous skin cancer or very early stage cancer.

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It's been less than 28 days since my last experimental treatment.

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I am not pregnant or breastfeeding and have a negative pregnancy test.

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My brain or spinal cord lymphoma is in remission, confirmed by tests for at least 90 days.

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My tests show early signs of a bone marrow disorder.

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I have hepatitis but my PCR test for it is negative.

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I have HIV/AIDS.

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

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I have had a stem cell transplant from a donor.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 weeks after culture of uf-kure19 car-t cells

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 weeks after culture of uf-kure19 car-t cells

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 weeks after culture of uf-kure19 car-t cells for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Recommend dose(s) of UF-KURE19 CAR-T Cells

Toxicities associated with the target dose of UF-KURE19 CAR-T Cells

Secondary study objectives

Incidence of treatment- emergent AEs (TEAEs)

Overall Response

Rate of UF-KURE19 CAR-T cells manufacture success

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: UF-KURE19 CAR-T cell infusionExperimental Treatment3 Interventions

The safety and manufacturing feasability 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: 8.5 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: 5.5 x 10\^6 UF-KURE19 CAR-T Cell Dose * Level 1: 11.5 x 10\^6 UF-KURE19 CAR-T Cell Dose

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Fludarabine

2012

Completed Phase 4

~1860

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

CAR-T cell therapy, a prominent treatment for Non-Hodgkin's Lymphoma (NHL), involves modifying a patient's T cells to express chimeric antigen receptors (CARs) that target specific cancer cell proteins. This modification is typically achieved using a lentivirus to integrate the CAR gene into the T cells. Upon reinfusion, these engineered T cells can specifically recognize and destroy cancer cells. This targeted approach is crucial for NHL patients as it provides a potential for long-term remission, particularly in relapsed or refractory cases where conventional treatments have not been effective.