Tisagenlecleucel for Follicular Lymphoma

(LEDA Trial)

Recruiting at 35 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must not be taking: Anti-CD19, Gene therapy

Disqualifiers: CNS involvement, HIV, Hepatitis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Single infusion for tisagenlecleucel; duration varies for R2 or R-CHOP

108 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tisagenlecleucel, a type of CAR T-cell therapy, for individuals with relapsed or refractory follicular lymphoma. The researchers aim to determine if tisagenlecleucel is more effective than current treatments. Participants will be divided into groups to receive either the new treatment or standard care. The trial seeks adults with follicular lymphoma that has returned or not responded after at least two treatments. This trial may be suitable for those whose current treatments have failed and whose condition is active and measurable on scans. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if 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 tisagenlecleucel is likely to be safe for humans?

Research shows that tisagenlecleucel is generally well-tolerated by patients. In past studies, patients experienced manageable side effects. Common side effects included fever and tiredness, typical for this type of treatment. Importantly, serious side effects were rare.

The FDA has already approved tisagenlecleucel for other conditions, which increases confidence in its safety for patients. While every treatment carries risks, evidence suggests that the benefits of tisagenlecleucel may outweigh these risks for people with follicular lymphoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for follicular lymphoma, like R2 or R-CHOP, Tisagenlecleucel offers a groundbreaking approach by using CAR-T cell therapy. This means it works by taking a patient's own T-cells, genetically modifying them to target cancer cells, and then reintroducing them into the body. This personalized strategy is exciting because it harnesses the power of the immune system to potentially provide a long-lasting response, even after just a single infusion. Researchers are particularly hopeful about its ability to target and destroy cancer cells more effectively and with fewer side effects compared to traditional chemotherapy regimens.

What evidence suggests that tisagenlecleucel might be an effective treatment for follicular lymphoma?

Research has shown that tisagenlecleucel, which participants in this trial may receive, holds promise for treating follicular lymphoma that has returned or is unresponsive to other treatments. In the ELARA trial, 86% of patients experienced a reduction or disappearance of their cancer, and about 66% showed no detectable signs of cancer after treatment. This therapy uses CAR-T cells, specially altered immune cells that target cancer cells. These results suggest that tisagenlecleucel could be a strong option for people with challenging cases of follicular lymphoma. ^{1 2 4 5 6}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

Adults over 18 with relapsed or refractory follicular lymphoma, who have tried at least two systemic therapies including an anti-CD20 antibody and an alkylating agent. They must show active disease on PET and CT scans, be in fair health (ECOG 0-2), and have good organ function to participate.

Inclusion Criteria

My blood, kidney, liver, and lung functions are all within normal ranges.

I am eligible for standard cancer treatment.

My disease shows active on PET scan and is measurable on CT scan.

Exclusion Criteria

I do not have serious heart conditions like heart failure or abnormal heart rhythms.

My lymphoma is either grade 3B or has changed in its appearance under the microscope.

I have previously received treatments like anti-CD19, gene, or T-cell therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a single infusion of tisagenlecleucel or standard of care treatment (R2 or R-CHOP)

Single infusion for tisagenlecleucel; duration varies for R2 or R-CHOP

Follow-up

Participants are monitored for safety and effectiveness after treatment, with progression-free survival as the primary endpoint

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Tisagenlecleucel

Trial Overview The trial is testing Tisagenlecleucel against the standard of care treatments for follicular lymphoma. Standard care includes a combination of chemotherapy drugs (R-CHOP) or Lenalidomide plus Rituximab (R2). Participants will receive one treatment based on random assignment.

How Is the Trial Designed?

Group I: Tisagenlecleucel Experimental Treatment 3 Interventions

Participants randomized to the tisagenlecleucel treatment strategy will receive a single infusion of 0.6 to 6 x 10\^8 CAR-positive viable T-cells

Group II: R2 or R-CHOP Active Control 2 Interventions

Participants randomized to Standard of Care treatment will receive either R2 or R-CHOP based on investigator choice of therapies, and this has to be determined prior to randomization.

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

Approved in United States as Kymriah for:

• B-cell acute lymphoblastic leukemia (ALL) in patients up to 25 years old
• 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 Kymriah for:

• B-cell acute lymphoblastic leukemia (ALL) in patients up to 25 years old
• Relapsed or refractory diffuse 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

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In the ELARA phase 2 trial involving 98 patients with relapsed/refractory follicular lymphoma, tisagenlecleucel demonstrated a complete response rate of 69.1% and an overall response rate of 86.2%, indicating its efficacy in this patient population.

The treatment was found to be safe, with manageable side effects; 48.5% of patients experienced cytokine release syndrome, but there were no treatment-related deaths, highlighting its safety profile even in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Fowler, NH., Dickinson, M., Dreyling, M., et al.[2022]

Tisagenlecleucel has been found to be both safe and effective for adults suffering from relapsed or refractory follicular lymphoma, indicating its potential as a treatment option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel Is Safe and Effective in Relapsed/Refractory Follicular Lymphoma. [2022]

In a study of 37 adult patients undergoing CAR T-cell therapy for relapsed/refractory large B-cell lymphoma, 24% had their manufactured tisagenlecleucel (tisa-cel) classified as out-of-commercial specification (OOS).

Among the patients with OOS tisa-cel, 44% received academic point-of-care CAR T-cell therapy as a salvage option, with 75% of those achieving a complete response, highlighting the potential effectiveness of alternative therapies in this scenario.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Point-of-care CAR T-cell therapy as salvage strategy for out-of-specification tisagenlecleucel. Fried, S., Shouval, R., Varda-Bloom, N., et al.[2023]

In a study of 32 patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) treated with tisagenlecleucel (tisa-cel), the level of CAR-T cell expansion in the body after treatment was found to be a key predictor of therapy success, rather than the specific characteristics of the CAR-T cells themselves.

Patients who had a higher percentage of certain T cell types (CD8+CD45RA+CD27+) before treatment were more likely to respond positively to the therapy, while those with primary refractory aggressive B-cell lymphomas showed poor outcomes, indicating that tumor biology plays a significant role in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of the input material quality for the production of tisagenlecleucel by multiparameter flow cytometry and its relation to the clinical outcome. Štach, M., Pytlík, R., Šmilauerová, K., et al.[2023]

Tisagenlecleucel (tisa-cel) is an effective CAR-T therapy for patients with relapsed/refractory follicular lymphoma (R/R FL), showing durable remissions even in high-risk patients, as confirmed by the pivotal ELARA study.

The therapy has a manageable toxicity profile, making it a viable option for patients who have undergone two lines of systemic therapies, leading to its FDA approval for this indication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel: CAR-T cell therapy for adult patients with relapsed or refractory follicular lymphoma. Saha, A., Jhaveri, K., Sarfraz, H., et al.[2023]

Secondary central nervous system (CNS) lymphoma patients may achieve long-term remission with CAR-T cell therapies Axi-cel and Tisa-cel, although their progression-free and overall survival rates tend to be shorter compared to non-CNS patients.

The safety profile of CAR-T cell therapy in secondary CNS lymphoma patients is comparable to that of non-CNS patients, with no reported CAR-T cell-related deaths, suggesting that the treatment is manageable in terms of risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Axicabtagene Ciloleucel and Tisagenlecleucel Administration in Lymphoma Patients With Secondary CNS Involvement: A Systematic Review. Wu, X., Zhang, X., Xun, R., et al.[2021]

In a study of 91 patients with relapsed/refractory large B-cell lymphoma (LBCL), treatment with the CAR T-cell therapy tisagenlecleucel (tisa-cel) resulted in a best overall response rate of 60% and a complete response rate of 32%, indicating its efficacy in a real-world setting.

The safety profile of tisa-cel was manageable, with only 5% of patients experiencing severe cytokine release syndrome and 1% experiencing neurotoxicity, suggesting that it can be safely administered in standard-of-care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. Iacoboni, G., Villacampa, G., Martinez-Cibrian, N., et al.[2021]

Citations

1. kymriah-hcp.com kymriah-hcp.com/follicular-lymphoma-adults/efficacy

FL Efficacy Data | KYMRIAH® (tisagenlecleucel) | HCP Find efficacy results and clinical data for KYMRIAH as a treatment option for Follicular Lymphoma. See full Prescribing & Safety Info, including Boxed ...

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

Kymriah® (tisagenlecleucel) – An overview of the clinical ... This article presents a high-level overview of the clinical development journey of tisagenlecleucel, including its efficacy outcomes and safety considerations.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03568461

NCT03568461 | Efficacy and Safety of Tisagenlecleucel in ... This is a multi-center, phase II study to determine the efficacy and safety of tisagenlecleucel in adult patients with relapsed or refractory FL.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35973192/

Efficacy comparison of tisagenlecleucel vs usual care in ... The ELARA trial indicates tisagenlecleucel (tisa-cel) is an effective anti-CD19 chimeric antigen receptor T-cell therapy for relapsed or ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02375-5/fulltext

805MO Real-world efficacy and safety of tisagenlecleucel ... The phase 2 ELARA clinical trial, with a median follow-up of 29 months, demonstrated a high overall response rate (ORR) of 86% with a complete response rate ( ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4398/532389/Efficacy-and-Safety-of-Tisagenlecleucel-in

Efficacy and Safety of Tisagenlecleucel in Patients with ... However, there are limited data regarding outcomes of r/r FL pts treated with commercial tisagenlecleucel. Here we present the first real-world ...