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

Recruiting at 81 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

1000 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial aims to understand the safety and effectiveness of specialized cancer treatments in participants of Kite-sponsored studies. These treatments work by modifying patients' immune cells to better fight cancer.

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 data supports the effectiveness of the treatment Axicabtagene Ciloleucel (Yescarta) for cancer?

Axicabtagene ciloleucel (Yescarta) is a genetically engineered T-cell therapy approved for adults with relapsed or refractory large B-cell lymphoma, showing effectiveness where other treatments have failed. It was the first such therapy approved by the FDA for these types of cancers, which had not seen new approved treatments in over 40 years. ^{1 2 3 4 5}

What safety data exists for gene-modified cell therapy like Axicabtagene Ciloleucel?

Axicabtagene ciloleucel, a type of gene-modified cell therapy, has been studied for safety in patients with large B-cell lymphoma. While it shows good effectiveness, it can cause adverse reactions, which are being closely monitored in clinical settings. ^{2 4 6 7 8}

How is the treatment Axicabtagene Ciloleucel unique for cancer?

Axicabtagene Ciloleucel is a unique cancer treatment because it is a chimeric antigen receptor (CAR) T-cell therapy that uses the patient's own genetically modified T cells to target and destroy cancer cells, specifically those expressing the CD19 antigen. This approach is novel as it represents a 'living drug' that is personalized for each patient, offering a new option for those with relapsed or refractory large B-cell lymphoma after other treatments have failed. ^{2 4 5 7 9}

Research Team

Kite Study Director

Principal Investigator

Kite, A Gilead Company

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. France 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)]. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Development and Use of the Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy Axicabtagene Ciloleucel in Large B-Cell Lymphoma: A Review. [2021]

3. France 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. [2021]

4. Germany pubmed.ncbi.nlm.nih.gov

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. [2021]

5. France 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]. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Ciltacabtagene Autoleucel in Patients With Prior Allogeneic Stem Cell Transplant in the CARTITUDE-1 Study. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

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

9. United States 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. [2022]