Tisagenlecleucel for Follicular Lymphoma

(ELARA Trial)

No longer recruiting at 56 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must not be taking: Anti-CD19, Gene therapy

Disqualifiers: Histologic transformation, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called tisagenlecleucel, a type of gene therapy, to determine its safety and effectiveness for adults with follicular lymphoma that has returned or is unresponsive to treatment. Follicular lymphoma is a blood cancer affecting the lymphatic system. The trial targets individuals whose disease is visible on scans and who have specific types of follicular lymphoma (Grades 1, 2, or 3A). Those who have received certain previous treatments, such as anti-CD19 therapy or gene therapy, or have cancer that has spread to the brain, are not eligible for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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 tisagenlecleucel is likely to be safe for humans?

Research has shown that tisagenlecleucel is generally safe for people with relapsed or refractory follicular lymphoma (FL). One study found that it caused fewer serious side effects compared to a similar treatment. Over a follow-up period of 29 months, it continued to demonstrate good safety results.

Real-world data supports these findings, showing excellent response rates and a positive safety profile. Overall, the treatment appears well-tolerated, with many patients experiencing manageable side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for follicular lymphoma, which typically involve chemotherapy and immunotherapy, tisagenlecleucel offers a novel approach by using CAR-T cell therapy. This treatment involves reprogramming a patient's own T cells to target and destroy cancer cells, making it a personalized form of therapy. Researchers are excited about tisagenlecleucel because it has the potential to provide long-lasting remission with just a single infusion, which could be a game-changer for patients who have exhausted other options. Additionally, its targeted mechanism of action may result in fewer side effects compared to traditional treatments.

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

Research has shown that tisagenlecleucel, the treatment under study in this trial, holds promise for treating follicular lymphoma. In one study, 69.1% of patients treated with tisagenlecleucel had no detectable cancer, compared to only 17.7% of those receiving standard care. The overall response rate, including those with partial improvement, was 85.6% for tisagenlecleucel. Additionally, the median time without cancer worsening was 53.3 months. These findings suggest that the treatment could be an effective option for people with follicular lymphoma that has returned or not responded to other treatments. ^{1 2 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with Follicular Lymphoma grades 1, 2, or 3A that hasn't responded to treatment or has come back. Participants must have measurable disease. Those with transformed lymphoma, brain involvement by cancer, previous stem cell transplant, grade 3B lymphoma, or prior gene or anti-CD19 therapy can't join.

Inclusion Criteria

Radiographically measurable disease at screening

My Follicular Lymphoma has returned or is not responding to treatment.

Exclusion Criteria

I have had a stem cell transplant from a donor.

I have had adoptive T cell therapy before.

I have received gene therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants may undergo optional bridging therapy and lymphodepleting chemotherapy

2-4 weeks

Treatment

Participants receive tisagenlecleucel infusion

1 day

Follow-up

Participants are monitored for safety and efficacy, including survival follow-up every 3 months

24 months

What Are the Treatments Tested in This Trial?

Interventions

• tisagenlecleucel

Trial Overview The study tests the effectiveness and safety of a drug called tisagenlecleucel in treating Follicular Lymphoma that's either stopped responding to standard treatments or has returned after treatment.

How Is the Trial Designed?

Group I: CTL019 Experimental Treatment 1 Intervention

All patients who received tisagenlecleucel infusion.

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 a phase 3 trial with 322 patients suffering from aggressive B-cell non-Hodgkin's lymphoma, tisagenlecleucel did not show superior efficacy compared to standard salvage chemotherapy and autologous stem-cell transplantation, with both groups having a median event-free survival of 3.0 months.

Response rates were similar between the two groups, with 46.3% of patients receiving tisagenlecleucel responding compared to 42.5% in the standard-care group, indicating that while tisagenlecleucel is a treatment option, it may not provide additional benefits over existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. Bishop, MR., Dickinson, M., Purtill, D., et al.[2022]

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 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]

Citations

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

805MO Real-world efficacy and safety of tisagenlecleucel ... The 12-month progression-free survival (PFS) and overall survival (OS) rates were 62.6% and 84.9%, respectively (both medians were not reached). Among the 106 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37345672/

Effectiveness of tisagenlecleucel versus real-world ... Results: Complete response rate was 69.1 versus 17.7% and the overall response rate was 85.6 versus 58.1% in tisagenlecleucel versus SoC, post ...

3. 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 ... Efficacy outcomes included ORR, CRR, progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Key safety outcomes ...

4. 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 ...

5. targetedonc.com targetedonc.com/view/tisagenlecleucel-efficacy-in-r-r-follicular-lymphoma-sustained-with-4-year-update

Tisagenlecleucel Efficacy in R/R Follicular Lymphoma ... The median progression-free survival (PFS) was 53.3 months (95% CI,18.2–not evaluable). The 4-year PFS rates were 50.2% overall and 66.1% in ...

6. 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.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38194692/

Durable response after tisagenlecleucel in adults with ... Tisagenlecleucel continued to demonstrate highly durable efficacy and a favorable safety profile in this extended follow-up of 29 months in patients with r/r ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38179688/

Comparative efficacy and safety of tisagenlecleucel and ... Tisa-cel (n = 53) was associated with better safety outcomes than axi-cel (n = 124), reflected by lower rates of any grade and grade ≥3 cytokine release ...