Long-Term Safety of Gene-Modified Cell Therapy for Cancer

Enrolling by invitation at 96 trial locations

Overseen By Medical Information

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Kite, A Gilead Company

Must be taking: Gene-modified cells

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to assess the long-term safety and effectiveness of several gene-modified cell therapies for people with cancer. The study will evaluate treatments like axicabtagene ciloleucel (Yescarta) and brexucabtagene autoleucel (Tecartus) to determine their performance over time and ensure continued safety. It specifically targets participants who have already received one of these therapies in a previous study and are willing to continue follow-up. Those who participated in an earlier Kite-sponsored study and received one of these treatments might be a good fit for this trial. As a Phase 4 trial, the study focuses on treatments already FDA-approved and proven effective, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What is the safety track record for these treatments?

In a previous study, axicabtagene ciloleucel demonstrated a manageable safety profile over two years. Serious issues, such as severe brain problems, were rare. However, some patients experienced serious side effects like seizures and confusion, requiring quick medical attention.

For brexucabtagene autoleucel, studies found it can cause serious side effects, including cytokine release syndrome (CRS), a potentially life-threatening reaction needing immediate care. Some patients also had severe allergic reactions and neurological problems.

Research on KITE-222 has primarily focused on understanding its safety and dosage, with detailed safety data still being collected.

KITE-363 has shown a tolerable safety profile with manageable side effects. Common issues included a drop in white blood cells, which help fight infections, but no major dose-limiting problems were reported.

For KITE-439 and KITE-585, data is limited, but ongoing studies are examining their safety and effectiveness. Early reports have not highlighted severe safety concerns.

KITE-718 is under study for safety, with researchers still determining the best dose. No major safety issues have been reported so far.

Lastly, KITE-753 and KITE-197 are in early studies. Researchers are focusing on understanding their safety and dose levels. Like the others, no major safety concerns have been reported yet.

These treatments are carefully monitored to ensure safety. Participants in these studies are closely watched for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these gene-modified cell therapies because they offer a personalized approach to treating cancer, using the patient's own immune cells to fight the disease. Unlike traditional chemotherapy or radiation, these treatments, such as Axicabtagene Ciloleucel and Brexucabtagene Autoleucel, involve modifying the patient's T-cells to specifically target and destroy cancer cells, which can lead to more precise and effective treatment. The unique mechanism of targeting cancer cells directly could potentially result in fewer side effects and a higher success rate compared to conventional therapies. Additionally, treatments like KITE-222 and KITE-718 are designed to target specific proteins on cancer cells, making them a promising option for hard-to-treat cancers.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that axicabtagene ciloleucel, one of the treatments in this trial, can lead to long-lasting improvements in patients with difficult-to-treat large B-cell lymphoma. Studies indicate high survival rates, with some patients living more than five years. Brexucabtagene autoleucel, another treatment option in this trial, has demonstrated strong, lasting improvements in patients with relapsed or hard-to-treat mantle cell lymphoma. Real-world data suggests it is effective and generally safe. KITE-363, also part of this trial, targets specific proteins on cancer cells to prevent them from evading treatment, showing high response rates without severe side effects. Each treatment has promising evidence supporting its effectiveness for certain cancer types. ^{1 3 6 7 8}

Who Is on the Research Team?

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Are You a Good Fit for This Trial?

This trial is for people who have had blood or other cancers and were treated with gene-modified cells in previous Kite-sponsored studies. They should be able to follow the study plan and agree to all required check-ups. Participants must understand and sign a consent form.

Inclusion Criteria

In the investigator's judgment, the individual is willing and able to complete the protocol-required follow-up schedule and comply with the study requirements for participation

The individual must have received an infusion of gene-modified cells in a completed Kite-sponsored parent study, has not withdrawn full consent, and has discontinued or completed the post-treatment follow-up period in the parent study, as applicable

The individual must understand and voluntarily sign an Informed Consent Form (ICF) or an Informed Assent Form prior to any study-related assessments or procedures being conducted

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Long-term Follow-up

Participants are monitored for long-term safety, effectiveness, and prolonged action of Kite study drugs

Up to 15 years

Survival Status Assessment

Survival status will be assessed as the length of time from the participant's first dose date of study drug to death during the study due to any cause or last date of being alive during the study

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Axicabtagene Ciloleucel
• Brexucabtagene Autoleucel
• Brexucabtagene Autoleucel (KTE-X19)
• KITE-222
• KITE-363
• KITE-439
• KITE-585
• KITE-718

Trial Overview

The study aims to assess the long-term effects of several gene therapies (Axicabtagene Ciloleucel, Brexucabtagene Autoleucel, KITE-585, etc.) previously administered to participants in earlier trials by Kite Pharma.

How Is the Trial Designed?

Group I: KITE-753 Experimental Treatment 1 Intervention

All participants who previously received KITE-753 in the parent study will be enrolled in this cohort for long-term follow-up.

Group II: KITE-363 Experimental Treatment 1 Intervention

All participants who previously received KITE-363 in the parent study will be enrolled in this cohort for long-term follow-up.

Group III: KITE-197 Experimental Treatment 1 Intervention

All participants who previously received KITE-197 in the parent study will be enrolled in this cohort for long-term follow-up.

Group IV: Brexucabtagene Autoleucel (KTE-X19) Experimental Treatment 1 Intervention

All participants who previously received brexucabtagene autoleucel (KTE-X19) in the parent study will be enrolled in this cohort for long-term follow-up.

Group V: Axicabtagene Ciloleucel (KTE-C19) Experimental Treatment 1 Intervention

All participants who previously received axicabtagene ciloleucel (KTE-C19) in the parent study will be enrolled in this cohort for long-term follow-up.

Group VI: Anitocabtagene autleucel Experimental Treatment 1 Intervention

All participants who previously received anitocabtagene autleucel in the parent study will be enrolled in this cohort for long-term follow-up.

Axicabtagene Ciloleucel is already approved in United States, European Union for the following indications:

Approved in United States as Yescarta for:

• Large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy
• Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy
• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Approved in European Union as Yescarta for:

• Diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy
• Relapsed or refractory DLBCL and primary mediastinal large B-cell lymphoma, after two or more lines of systemic therapy
• Relapsed or refractory follicular lymphoma after three or more lines of systemic therapy

Who Is Running the Clinical Trial?

Kite, A Gilead Company

Lead Sponsor

Trials

45

Recruited

4,300+

Published Research Related to This Trial

CAR T-cell therapies, such as tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), are effective treatments for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, utilizing genetically modified T cells that target the CD19 antigen.

These therapies are classified as 'living drugs' because they involve the genetic engineering of a patient's own T cells, highlighting the importance of proper collection and manufacturing processes for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. Carnoy, S., Beaumont, JL., Kanouni, T., et al.[2021]

A survey of 41 experienced clinicians revealed that many do not consider a history of malignancy or prior treatments as contraindications for CAR T-cell therapy, indicating a broader eligibility for patients than previously thought.

There is significant variability in follow-up care models after CAR T therapy, with most clinicians recommending frequent hospital visits in the initial month, highlighting the need for standardized guidelines in patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An international survey on the management of patients receiving CAR T-cell therapy for haematological malignancies on behalf of the Chronic Malignancies Working Party of EBMT. Hayden, PJ., Sirait, T., Koster, L., et al.[2021]

Cytokine release syndrome (CRS) is the most common adverse reaction reported after CAR-T therapy, with significantly higher reports for axicabtagene ciloleucel compared to tisagenlecleucel, indicating a need for careful monitoring of this side effect.

The study analyzed 1426 reports of adverse drug reactions from real clinical settings, supporting the overall safety profile of CAR-T therapies while confirming CRS as a major concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. Bonaldo, G., Montanaro, N., AlbertoVaccheri, ., et al.[2021]

In a retrospective study of 275 patients with relapsed/refractory large B-cell lymphoma (LBCL) receiving axicabtagene ciloleucel (axi-cel), the overall response rate was 82% and the complete response rate was 64%, demonstrating strong efficacy similar to the original ZUMA-1 trial.

Safety profiles showed that 7% of patients experienced severe cytokine release syndrome and 31% had neurotoxicity, with a nonrelapse mortality rate of 4.4%, indicating manageable risks associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. Nastoupil, LJ., Jain, MD., Feng, L., et al.[2022]

Tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™) are pioneering CAR-T cell therapies that involve modifying a patient's own T cells to target cancer, marking a significant advancement in gene therapy.

The establishment of multiple CAR-T cell databases in France aims to enhance data collection and quality for patients treated with these therapies, which is crucial for ongoing research and improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A standardized medical report template for CAR T-Cell therapy patients: Guidelines of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. Broussais, F., Vasseur, A., Karam, M., et al.[2022]

In a retrospective analysis of 7 patients with prior allogeneic stem cell transplants (alloSCT) who received cilta-cel, an overall response rate of 85.7% was observed, indicating that cilta-cel is effective even in this heavily pretreated group.

The safety profile of cilta-cel in patients with prior alloSCT was similar to that of patients without alloSCT, with manageable side effects like cytokine release syndrome and no reported cases of graft-versus-host disease, suggesting that cilta-cel may be a viable treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene Autoleucel in Patients With Prior Allogeneic Stem Cell Transplant in the CARTITUDE-1 Study. Htut, M., Dhakal, B., Cohen, AD., et al.[2023]

Axicabtagene ciloleucel (Yescarta) is an approved second-line treatment for patients with large B-cell lymphoma who do not respond to or relapse within 12 months of initial chemoimmunotherapy.

Patient identity confirmation and premedication to reduce hypersensitivity reactions are essential steps in the administration of this autologous infusion therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Second-Line Treatment for B-Cell Lymphoma. Aschenbrenner, DS.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6733402/

Long-term safety and activity of axicabtagene ciloleucel in ...

These 2-year follow-up data from ZUMA-1 suggest that axicabtagene ciloleucel can induce durable responses and a median overall survival of ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6990602/

Safety and efficacy of axicabtagene ciloleucel in refractory ...

We provide an overview of axi-cel therapy, including efficacy and safety data, along with a practical discussion of current treatment considerations.

3.

bloodcancerunited.org

bloodcancerunited.org/research/therapy-acceleration-program-tap/yescarta-tap-supported-fda-approval

Yescarta - LLS TAP supported FDA approval

Yescarta® Is First CAR T-cell Therapy to Report Five-Year Survival Data From Pivotal Study Showing Durable Long-Term Survival in Patients With Refractory Large ...

4.

kitepharma.com

kitepharma.com/news/press-releases/2023/12/long-term-data-for-kites-yescarta-car-t-cell-therapy-presented-at-ash-2023-demonstrate-high-rate-of-durable-response-in-patients-with-high-risk-larg

Long-Term Data for Kite's Yescarta® CAR T-Cell Therapy ...

At median follow-up of 40.9 months, patients treated with Yescarta experienced an 86% complete response rate and the three-year estimate for overall survival ...

5.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa1707447

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory ...

Ongoing durable remissions have been observed in patients at 24 months. These results, combined with the observation of ongoing long-term ...

6.

yescartahcp.com

yescartahcp.com/large-b-cell-lymphoma/safety

Safety - YESCARTA® (axicabtagene ciloleucel)

Prolonged encephalopathy lasting up to 173 days was noted. Serious events, including aphasia, leukoencephalopathy, dysarthria, lethargy, and seizures occurred.

7.

mayoclinic.org

mayoclinic.org/drugs-supplements/axicabtagene-ciloleucel-intravenous-route/description/drg-20406587

Axicabtagene ciloleucel (intravenous route) - Side effects & ...

This medicine may cause cytokine release syndrome (CRS) and infusion reactions. This may be life-threatening and requires immediate attention.

8.

fda.gov

fda.gov/media/108377/download

Package Insert and Medication Guide - YESCARTA

Fatal and serious cases of cerebral edema and encephalopathy, including late-onset encephalopathy, have occurred in patients treated with YESCARTA.