Tisagenlecleucel for Follicular Lymphoma

(LEDA Trial)

Recruiting at 27 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

Trial Summary

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.

What data supports the effectiveness of the treatment Tisagenlecleucel for Follicular Lymphoma?

Research shows that Tisagenlecleucel is effective for adults with relapsed or refractory follicular lymphoma, with studies confirming its high efficacy and manageable side effects, leading to FDA approval for this condition. ^{1 2 3 4 5}

Is Tisagenlecleucel (Kymriah) safe for use in humans?

Tisagenlecleucel (also known as Kymriah or tisa-cel) has been shown to have a manageable safety profile in treating certain types of lymphoma, with some patients experiencing serious side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage), but these were relatively rare. The treatment has been used safely in both clinical trials and real-world settings for conditions like relapsed or refractory large B-cell lymphoma and follicular lymphoma. ^{1 3 4 5 6}

How is the treatment Tisagenlecleucel unique for follicular lymphoma?

Tisagenlecleucel is a unique treatment for follicular lymphoma because it is a CAR-T cell therapy that uses the patient's own immune cells, modified to target and destroy cancer cells. This approach is different from traditional chemotherapy or radiation, as it specifically targets the CD19 protein on cancer cells, offering a personalized and potentially more effective treatment option for patients who have not responded to other therapies. ^{1 3 5 6 7}

What is the purpose of this trial?

This trial will compare tisagenlecleucel to standard of care in adult participants with relapsed or refractory (r/r) follicular lymphoma.

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

I am eligible for standard cancer treatment.

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel: CAR-T cell therapy for adult patients with relapsed or refractory follicular lymphoma. [2023]

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

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

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

Point-of-care CAR T-cell therapy as salvage strategy for out-of-specification tisagenlecleucel. [2023]

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

Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Axicabtagene Ciloleucel and Tisagenlecleucel Administration in Lymphoma Patients With Secondary CNS Involvement: A Systematic Review. [2021]

6. Switzerland 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. [2023]

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

Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. [2022]