GM T Cell Therapy Long-Term Follow-Up for Cancer

Recruiting at 229 trial locations

Overseen By Taewoong Choi, Site 01175

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Celgene

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Varies based on prior study

1541 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective study for the long-term follow-up (LTFU) of safety and efficacy for all pediatric and adult participants exposed to Gene-modified (GM) T-cell therapy participating in a previous Celgene sponsored or Celgene alliance partner sponsored study. Participants who received at least one infusion of GM T cells will be asked to enroll in this LTFU protocol upon either premature discontinuation from, or completion of the prior parent treatment protocol.

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 trial coordinators or your doctor.

What data supports the effectiveness of the treatment Kymriah (tisagenlecleucel) for cancer?

Kymriah (tisagenlecleucel) is approved for treating certain types of relapsed or refractory cancers, like pediatric acute lymphoblastic leukemia and large B-cell lymphoma, showing it can be effective in these conditions. It has been shown to achieve high response rates and durable remissions in patients, indicating its potential effectiveness. ^{1 2 3 4 5}

What safety data exists for GM T Cell Therapy (Tisagenlecleucel/Kymriah)?

Tisagenlecleucel, a type of gene-modified T cell therapy, has been associated with some serious side effects, including cytokine release syndrome (a severe immune reaction) and neurological issues, but these can be managed by trained medical teams. Most adverse events are serious, but they are often related to the underlying cancer rather than the treatment itself. Long-term safety monitoring is ongoing to better understand and manage these risks. ^{1 6 7 8 9}

How does GM T Cell Therapy differ from other cancer treatments?

GM T Cell Therapy is a type of CAR T-cell therapy, which involves modifying a patient's own T cells to better recognize and attack cancer cells. This approach is unique because it uses the patient's immune system to target cancer, unlike traditional treatments like chemotherapy or radiation that directly attack cancer cells but can also harm healthy cells. ^{1 2 9 10 11}

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

This trial is for pediatric and adult patients who have previously received gene-modified (GM) T cell therapy in a Celgene sponsored or alliance partner study. Participants must have completed or discontinued the prior treatment protocol and be willing to sign an informed consent form.

Inclusion Criteria

I've had a gene-modified T-cell infusion in a past Celgene study and completed the follow-up.

Must understand and voluntarily sign an Informed Consent Form/Informed Assent Form prior to any study-related assessments/procedures being conducted

Exclusion Criteria

This criterion does not apply to me.

Other protocol-defined inclusion/exclusion criteria apply

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Gene-modified (GM) T cell therapy as part of a previous study

Varies based on prior study

Long-term Follow-up

Long-term follow-up of safety and efficacy for participants exposed to GM T cell therapy

Up to 15 years

Annual monitoring visits

Treatment Details

Interventions

• Gene-modified (GM) T cell therapy

Trial Overview The study focuses on long-term follow-up of safety and efficacy for those who underwent GM T cell therapy. It's designed to monitor participants after they've finished their initial treatment, tracking any long-term effects.

Participant Groups

Group I: Participants exposed to Gene-modified (GM) T cell therapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

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Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Findings from Research

Kymriah® (tisagenlecleucel) is an approved CD19-directed T-cell therapy that has transformed treatment for relapsed/refractory pediatric and young adult acute lymphoblastic leukemia, as well as certain types of lymphoma.

The therapy is based on genetically modifying a patient's own T-cells, showcasing a novel approach in oncology that emphasizes personalized medicine and has shown significant efficacy in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kymriah® (tisagenlecleucel) - An overview of the clinical development journey of the first approved CAR-T therapy. Awasthi, R., Maier, HJ., Zhang, J., et al.[2023]

YTB323, a new CAR T-cell therapy targeting CD19, demonstrated high overall response rates and durable complete remissions in a first-in-human study, indicating its potential effectiveness in treating certain cancers.

The therapy was shown to have a good safety profile and required cell doses that were up to 25-fold lower than those used in the previously established treatment, tisagenlecleucel, suggesting a more efficient approach to CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Express Delivery of Next-Generation CAR T Cells with Preserved Naive and Stemness Phenotypes for the Treatment of Aggressive Lymphomas. Wang, M.[2023]

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]

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 study of 374 patients receiving CAR T-cell therapy, European patients experienced significantly longer time from indication to infusion (66 days) compared to US patients (50 days), which is associated with inferior survival outcomes.

European patients also had higher baseline levels of lactate dehydrogenase and ferritin, and showed poorer progression-free survival (3.1 months) compared to US patients (9.2 months), indicating that higher tumor burden and systemic inflammation may negatively impact treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inferior Outcomes of EU Versus US Patients Treated With CD19 CAR-T for Relapsed/Refractory Large B-cell Lymphoma: Association With Differences in Tumor Burden, Systemic Inflammation, Bridging Therapy Utilization, and CAR-T Product Use. Bücklein, V., Perez, A., Rejeski, K., et al.[2023]

Tisagenlecleucel, an anti-CD19 CAR-T cell therapy, has been approved for treating pediatric and young adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL), showing significant long-term effectiveness and overall survival benefits.

While CAR-T cell therapy can lead to serious adverse events like cytokine release syndrome and neurological toxicities, these effects are manageable with proper medical training and protocols, highlighting the importance of specialized care in administering this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-T Cell Therapy: Practical Considerations for Implementation in Europe. Buechner, J., Kersten, MJ., Fuchs, M., et al.[2020]

In a review of 646 adverse event reports for the CAR T-cell therapy tisagenlecleucel from August 2017 to August 2019, the most common adverse event was cytokine release syndrome (CRS), reported in 51.1% of cases, with a serious outcome in over 95% of reports.

Despite the high reporting rate of adverse events (81.0%), most deaths (64%) were due to the progression of the underlying disease rather than the therapy itself, indicating that no new safety concerns were identified post-marketing, and the rates of CRS and neurotoxicity were lower than those observed in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events reported to the U.S. Food and Drug Administration Adverse Event Reporting System for tisagenlecleucel. Dores, GM., Jason, C., Niu, MT., 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 and axicabtagene ciloleucel, are effective treatments for certain types of blood cancers, specifically targeting the CD19 antigen in patients with relapsed or refractory conditions.

The recommendations provided by the European Society of Blood and Marrow Transplantation cover comprehensive patient care aspects, including eligibility, treatment procedures, and management of potential complications, ensuring a structured approach to administering these innovative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). Yakoub-Agha, I., Chabannon, C., Bader, P., et al.[2022]

Tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™) are the first CAR-T therapies approved, requiring long-term follow-up of 15 years to assess their safety and efficacy in real-world conditions.

The European Society for Blood and Marrow Transplantation (EBMT) is establishing a registry to track outcomes of CAR-T Cell treatments across EU countries, which will help evaluate the medical value and pricing justification of these innovative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Reporting data of patients receiving CAR T cell therapy into the EBMT registry: Guidelines of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. Vasseur, A., Karam, M., Chaillou, D., et al.[2021]

Tisagenlecleucel is a CAR-T cell therapy effective for treating relapsed/refractory B-cell precursor acute lymphoblastic leukemia in pediatric and young adult patients, as well as relapsed/refractory diffuse large B-cell lymphoma in adults.

Nurses play a crucial role in the outpatient administration and post-infusion care of tisagenlecleucel therapy, requiring thorough education on the treatment and adverse event management to ensure effective communication and patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel Therapy: Nursing Considerations for the Outpatient Setting. Cunningham, K., DiFilippo, H., Henes, K., et al.[2021]

References

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

Kymriah® (tisagenlecleucel) - An overview of the clinical development journey of the first approved CAR-T therapy. [2023]

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

Express Delivery of Next-Generation CAR T Cells with Preserved Naive and Stemness Phenotypes for the Treatment of Aggressive Lymphomas. [2023]

3. 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]

4. 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]

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

Inferior Outcomes of EU Versus US Patients Treated With CD19 CAR-T for Relapsed/Refractory Large B-cell Lymphoma: Association With Differences in Tumor Burden, Systemic Inflammation, Bridging Therapy Utilization, and CAR-T Product Use. [2023]

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

Chimeric Antigen Receptor-T Cell Therapy: Practical Considerations for Implementation in Europe. [2020]

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

Adverse events reported to the U.S. Food and Drug Administration Adverse Event Reporting System for tisagenlecleucel. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

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

9. Italy pubmed.ncbi.nlm.nih.gov

Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). [2022]

10. France pubmed.ncbi.nlm.nih.gov

[Reporting data of patients receiving CAR T cell therapy into the EBMT registry: Guidelines of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. [2021]

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

Tisagenlecleucel Therapy: Nursing Considerations for the Outpatient Setting. [2021]