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

Recruiting at 249 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the long-term safety and effectiveness of a special cancer treatment called gene-modified (GM) T cell therapy. It targets individuals who have already received at least one infusion of this therapy in a previous study. The goal is to assess the treatment's performance over time and ensure its safety for those who have previously tried it. Participants must have taken part in an earlier related trial and agreed to join this follow-up study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that gene-modified (GM) T cell therapy is generally safe for long-term use. One study examined safety data from 783 patients across 38 clinical trials and found over 2,200 years of patient observation without major safety issues. Another study confirmed that this therapy does not cause new cancers in patients.

Additionally, CD19-targeted CAR T cells, a type of GM T cell therapy, have helped patients with B cell cancers remain in remission longer, often with few long-term side effects. These findings suggest that GM T cell therapy is well-tolerated over time. While every treatment carries potential risks, these studies indicate that GM T cell therapy is generally safe for most people in the long run. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Gene-modified (GM) T cell therapy is unique because it harnesses the power of the body's own immune system to fight cancer, unlike traditional treatments like chemotherapy or radiation that attack cancer cells more broadly. This therapy involves altering T cells, a type of immune cell, to better recognize and destroy cancer cells. Researchers are excited about its potential because it offers a more targeted approach, potentially leading to fewer side effects and improved effectiveness in attacking cancer cells. Additionally, GM T cell therapy can be personalized for each patient, making it a cutting-edge option in cancer treatment.

What evidence suggests that Gene-modified (GM) T cell therapy might be an effective treatment for cancer?

Research has shown that Gene-modified (GM) T cell therapy, which participants in this trial will receive, holds promise for treating certain cancers. For instance, about 80% of patients who received a version of this therapy called Kymriah achieved MRD-negative remission, with no detectable cancer cells, within three months. In patients with different types of lymphoma, the therapy demonstrated a 64% overall response rate, with some achieving complete remission. Long-term data indicates that many patients remain cancer-free and have good survival rates up to two years after treatment. These findings strongly support the therapy's potential effectiveness in treating various cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

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

Published Research Related to This Trial

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 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 (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]

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]

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]

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 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]

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 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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10294746/

Kymriah® (tisagenlecleucel) – An overview of the clinical ...

Although a vast majority of pediatric and young adult patients with ALL have good long-term outcomes after conventional first-line therapy, approximately 15% of ...

2.

kymriah-hcp.com

kymriah-hcp.com/acute-lymphoblastic-leukemia-children/efficacy

KYMRIAH® (tisagenlecleucel) Efficacy Data & Clinical Trials

About 8/10 patients achieved minimal residual disease negative (MRD-negative) remission at 3 months after treatment with KYMRIAH (tisagenlecleucel).

3.

nature.com

nature.com/articles/s41392-025-02269-w

CAR-T cell therapy for cancer: current challenges and ...

2-targeted CAR has proven effective in treating gastrointestinal tumors in a study including 37 patients (NCT04196413), with an overall response ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6505546/

Tisagenlecleucel: The First CAR on the Highway to Remission ...

The overall response rate (ORR) was 64%; CR rates were 43% in patients with diffuse large B-cell lymphoma (DLBCL) and 71% in patients with follicular lymphoma, ...

5.

ashpublications.org

ashpublications.org/bloodadvances/article/9/20/5249/537901/Real-world-data-for-tisagenlecleucel-in-patients

Real-world data for tisagenlecleucel in patients with R/R B-ALL

The 12-month relapse-free survival (RFS) and overall survival (OS) were 61.8% and 79.4%, respectively, whereas the 24-month RFS and OS were 50.3% and 63.8%, ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10100620/

Long-term outcomes following CAR T cell therapy

The data demonstrate that CD19-targeted CAR T cells can induce prolonged remissions in patients with B cell malignancies, often with minimal long-term ...

7.

fda.gov

fda.gov/files/vaccines%2C%20blood%20%26%20biologics/published/Long-Term-Follow-Up-After-Admin-Human-GT-Products_Jan_2020.pdf

Long Term Follow-Up After Administration of Human Gene ...

We, FDA, are providing you, a sponsor who is developing a human gene therapy product (GT. Product),1 recommendations regarding the design of long term follow-up ...

8.

healio.com

healio.com/news/hematology-oncology/20250305/reassuring-study-shows-no-link-between-car-tcell-therapy-and-secondary-cancers

'Reassuring' study shows no link between CAR T-cell ...

“Our study really provides comprehensive long-term safety data that supports the continued clinical use of gene modified T-cell therapies ...

9.

emjreviews.com

emjreviews.com/hematology/news/study-highlights-long-term-safety-of-t-cell-gene-therapy/

Study Highlights Long-Term Safety of T Cell Gene Therapy

The study analysed safety data from 783 patients across 38 clinical trials, totalling over 2,200 patient-years of observation.

10.

nature.com

nature.com/articles/s41591-024-03478-6

Long-term safety of lentiviral or gammaretroviral gene- ...

In this study, we evaluated safety outcomes in 783 patients over more than 2,200 total patient-years of observation from 38 T cell therapy ...