Tisagenlecleucel for Follicular Lymphoma
(LEDA Trial)
Recruiting in Palo Alto (17 mi)
+26 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Novartis Pharmaceuticals
Must not be taking: Anti-CD19, Gene therapy
Disqualifiers: CNS involvement, HIV, Hepatitis, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Approved in 3 Jurisdictions
Trial Summary
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.
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.
12345Is 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.
13456How 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.
13567Eligibility 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.
+5 more
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.
+4 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: TisagenlecleucelExperimental Treatment3 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-CHOPActive Control2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Novartis Investigative SiteMontreal, Canada
Novartis Investigative SiteToronto, Canada
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Who Is Running the Clinical Trial?
Novartis PharmaceuticalsLead Sponsor
References
Tisagenlecleucel: CAR-T cell therapy for adult patients with relapsed or refractory follicular lymphoma. [2023]Tisagenlecleucel (tisa-cel) is an anti CD19 CAR-T therapy that has demonstrated clinical activity in R/R large B-cell lymphoma and R/R B-cell acute lymphoblastic leukemia. It showed particularly high efficacy in R/R follicular lymphoma (FL) with a manageable toxicity profile. The pivotal ELARA study in R/R FL confirmed these findings and led to the FDA approval of tisa-cel in R/R FL after two lines of systemic therapies.
Tisagenlecleucel Is Safe and Effective in Relapsed/Refractory Follicular Lymphoma. [2022]Tisagenlecleucel is safe and effective for adults with pretreated relapsed/refractory follicular lymphoma (FL).
Point-of-care CAR T-cell therapy as salvage strategy for out-of-specification tisagenlecleucel. [2023]Tisagenlecleucel (tisa-cel) is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for patients with relapsed/refractory large B-cell lymphoma. Outcomes of patients with out-of-commercial specification (OOS) CAR T products are not well characterized. We therefore assessed 37 adult patients who underwent leukapheresis for tisa-cel therapy in a single center. In nine (24%) patients, manufactured tisa-cel was considered OOS. Three of them (33%) received tisa-cel after institutional review board approval; 2/9 (22%) did not receive tisa-cel due to disease progression; and 4/9 (44%) received academic point-of-care (POC) CAR T-cell as salvage therapy, at a median of 35 days following OOS notification. Three of those four patients achieved a complete response. In univariate analysis, risk factors for OOS were ≥ 4 prior therapies or previous bendamustine exposure. In conclusion, we report high OOS incidence of 24% in real-life setting. Forty-four percent of those patients received POC CAR T-cell as salvage therapy.
Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. [2021]Tisagenlecleucel (tisa-cel) is a second-generation autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapy approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). The approval was based on the results of phase II JULIET trial, with a best overall response rate (ORR) and complete response (CR) rate in infused patients of 52% and 40%, respectively. We report outcomes with tisa-cel in the standard-of-care (SOC) setting for R/R LBCL. Data from all patients with R/R LBCL who underwent leukapheresis from December 2018 until June 2020 with the intent to receive SOC tisa-cel were retrospectively collected at 10 Spanish institutions. Toxicities were graded according to ASTCT criteria and responses were assessed as per Lugano 2014 classification. Of 91 patients who underwent leukapheresis, 75 (82%) received tisa-cel therapy. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 5% and 1%, respectively; non-relapse mortality was 4%. Among the infused patients, best ORR and CR were 60% and 32%, respectively, with a median duration of response of 8.9 months. With a median follow-up of 14.1 months from CAR T-cell infusion, median progression-free survival and overall survival were 3 months and 10.7 months, respectively. At 12 months, patients in CR at first disease evaluation had a PFS of 87% and OS of 93%. Patients with an elevated lactate dehydrogenase showed a shorter PFS and OS on multivariate analysis. Treatment with tisa-cel for patients with relapsed/refractory LBCL in a European SOC setting showed a manageable safety profile and durable complete responses.
Efficacy and Safety of Axicabtagene Ciloleucel and Tisagenlecleucel Administration in Lymphoma Patients With Secondary CNS Involvement: A Systematic Review. [2021]The efficacy and safety of chimeric antigen receptor T (CAR-T) cell therapy in the treatment of non-Hodgkin's lymphoma has already been demonstrated. However, patients with a history of/active secondary central nervous system (CNS) lymphoma were excluded from the licensing trials conducted on two widely used CAR-T cell products, Axicabtagene ciloleucel (Axi-cel) and Tisagenlecleucel (Tisa-cel). Hence, the objective of the present review was to assess whether secondary CNS lymphoma patients would derive a benefit from Axi-cel or Tisa-cel therapy, while maintaining controllable safety.
Characterization of the input material quality for the production of tisagenlecleucel by multiparameter flow cytometry and its relation to the clinical outcome. [2023]Tisagenlecleucel (tisa-cel) is a CD19-specific CAR-T cell product approved for the treatment of relapsed/refractory (r/r) DLBCL or B-ALL. We have followed a group of patients diagnosed with childhood B-ALL (n = 5), adult B-ALL (n = 2), and DLBCL (n = 25) who were treated with tisa-cel under non-clinical trial conditions. The goal was to determine how the intensive pretreatment of patients affects the produced CAR-T cells, their in vivo expansion, and the outcome of the therapy. Multiparametric flow cytometry was used to analyze the material used for manufacturing CAR-T cells (apheresis), the CAR-T cell product itself, and blood samples obtained at three timepoints after administration. We present the analysis of memory phenotype of CD4/CD8 CAR-T lymphocytes (CD45RA, CD62L, CD27, CD28) and the expression of inhibitory receptors (PD-1, TIGIT). In addition, we show its relation to the patients' clinical characteristics, such as tumor burden and sensitivity to prior therapies. Patients who responded to therapy had a higher percentage of CD8+CD45RA+CD27+ T cells in the apheresis, although not in the produced CAR-Ts. Patients with primary refractory aggressive B-cell lymphomas had the poorest outcomes which was characterized by undetectable CAR-T cell expansion in vivo. No clear correlation of the outcome with the immunophenotypes of CAR-Ts was observed. Our results suggest that an important parameter predicting therapy efficacy is CAR-Ts' level of expansion in vivo but not the immunophenotype. After CAR-T cells' administration, measurements at several timepoints accurately detect their proliferation intensity in vivo. The outcome of CAR-T cell therapy largely depends on biological characteristics of the tumors rather than on the immunophenotype of produced CAR-Ts.
Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. [2022]Tisagenlecleucel is an autologous anti-CD19 chimeric antigen receptor-T cell therapy with clinically meaningful outcomes demonstrated in patients with relapsed/refractory (r/r) B-cell lymphoma. In a previous pilot study of tisagenlecleucel in r/r follicular lymphoma (FL), 71% of patients achieved a complete response (CR). Here we report the primary, prespecified interim analysis of the ELARA phase 2 multinational trial of tisagenlecleucel in adults with r/r FL after two or more treatment lines or who relapsed after autologous stem cell transplant (no. NCT03568461). The primary endpoint was CR rate (CRR). Secondary endpoints included overall response rate (ORR), duration of response, progression-free survival, overall survival, pharmacokinetics and safety. As of 29 March 2021, 97/98 enrolled patients received tisagenlecleucel (median follow-up, 16.59 months; interquartile range, 13.8-20.21). The primary endpoint was met. In the efficacy set (n = 94), CRR was 69.1% (95% confidence interval, 58.8-78.3) and ORR 86.2% (95% confidence interval, 77.5-92.4). Within 8 weeks of infusion, rates of cytokine release syndrome were 48.5% (grade ≥3, 0%), neurological events 37.1% (grade ≥3, 3%) and immune effector cell-associated neurotoxicity syndrome (ICANS) 4.1% (grade ≥3, 1%) in the safety set (n = 97), with no treatment-related deaths. Tisagenlecleucel is safe and effective in extensively pretreated r/r FL, including in high-risk patients.