A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma

Follicular Lymphoma (FL) Clinical Trial

— LEDA  

Official title:

A Randomized, Open-label, Multi-center Phase III Trial Comparing Tisagenlecleucel to Standard of Care in Adult Participants With Relapsed or Refractory Follicular Lymphoma (FL)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05888493
• Other study ID #: CCTL019E2301
• Secondary ID: 2023-503452-27-0
• Status: Recruiting
• Phase: Phase 3
• Start date: October 2, 2023
• Est. completion date: February 7, 2029

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

The purpose of this phase III study is to verify the clinical benefit of tisagenlecleucel for the treatment of r/r FL by comparing the tisagenlecleucel treatment strategy to standard of care therapy in patients with r/r FL after two or more lines of systemic therapy, with progression-free survival (PFS) as the primary endpoint.

The primary objective is to demonstrate superiority of the tisagenlecleucel treatment strategy over standard of care (SOC) therapy with respect to progression-free survival (PFS) determined by blinded independent review committee (BIRC) based on the Lugano response criteria.

Participants randomized to Arm A (tisagenlecleucel treatment) will receive a single infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells.

Participants randomized to Arm B (Standard of Care) will receive R2 or R-CHOP based on investigator choice and this has to be determined prior to randomization.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: February 7, 2029
• Est. primary completion date: July 24, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age = 18 years at the date of signing the informed consent form.

2. Follicular lymphoma grade 1, 2, or 3A confirmed histologically after latest relapse (local assessment).

3. Relapsed or refractory disease after a second or later line of systemic therapy including an anti-CD20 antibody and an alkylating agent.

4. Disease that is both active on Positron emission tomography (PET) scan (defined as a score of 4 or 5 on the Deauville 5-point scale) and measurable on Computed tomography (CT) scan.

5. ECOG performance status of 0, 1 or 2 at screening.

6. Adequate hematologic, renal, hepatic and pulmonary organ function at screening.

7. Must meet the institutional criteria to undergo leukapheresis (unless historical leukapheresis is available).

8. Must be eligible for treatment with the selected standard of care regimen.

Exclusion Criteria:

1. Follicular lymphoma grade 3B or evidence of histologic transformation.

2. Prior treatment with anti-CD19 therapy, gene therapy, or adoptive T-cell therapy.

3. Active CNS involvement by malignancy.

4. Clinically significant active infection, presence of Human immunodeficiency virus (HIV) antibody or active hepatitis B or C.

5. Active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré syndrome).

6. Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to randomization.

7. Clinically significant cardiovascular conditions such as acute coronary syndrome, significant cardiac arrhythmias, heart failure or decreased LVEF.

Other protocol defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Follicular Lymphoma (FL)
• Lymphoma
• Lymphoma, Follicular

Intervention

Biological:
• Tisagenlecleucel
Tisagenlecleucel is a solution for infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells taken intravenously (i.v.).

Drug:
• Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles.
Lenalidomide 20 mg daily on days 1-21 for up to 12 cycles Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 2-5
• Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles
Rituximab 375 mg/m2 i.v. on day 1 Cyclophosphamide 750 mg/m2 i.v. day 1 Doxorubicin 50 mg/m2 i.v. day 1 Vincristine 1.4 mg/2 (capped at 2 mg) i.v. day 1 Prednisone or prednisolone 40 mg/m2 PO days 1-5
• Lymphodepleting chemotherapy
Fludarabine (25 mg/m^2 intravenously [i.v.] daily for 3 doses) OR Cyclophosphamide (250 mg/m^2 i.v. daily for 3 doses starting with the first dose of fludarabine). OR Bendamustine 90 mg/m^2 i.v. daily for 2 days (If there was previous grade IV hemorrhagic cystitis with cyclophosphamide, or the participant demonstrated resistance to a previous cyclophosphamide-containing regimen)

Other:
• Corticosteroids and/or Radiation (Bridging therapy)
Corticosteroids and/or Radiation

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Camperdown
Australia	Novartis Investigative Site	Clayton	Victoria
Australia	Novartis Investigative Site	Melbourne	Victoria
Czechia	Novartis Investigative Site	Ostrava	Poruba
Hungary	Novartis Investigative Site	Budapest
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Gliwice	Slaskie
Poland	Novartis Investigative Site	Lodz
Romania	Novartis Investigative Site	Bucharest
Singapore	Novartis Investigative Site	Singapore
Slovakia	Novartis Investigative Site	Bratislava	Slovak Republic
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	Hospitalet de LLobregat	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Salamanca	Castilla Y Leon
Spain	Novartis Investigative Site	Santander	Cantabria
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Australia,  Czechia,  Hungary,  Korea, Republic of,  Poland,  Romania,  Singapore,  Slovakia,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) determined by blinded independent review committee (BIRC)	Progression free survival (PFS) based on Lugano response criteria, defined as time from randomization to the first of the following events to occur: progressive disease (by BIRC); death from any cause	5 years
Secondary	Complete response rate (CRR) as assessed by BIRC (Key Secondary)	CRR: The proportion of participants with BOR of complete response (CR)	5 years
Secondary	Overall response rate (ORR) by BIRC	ORR: The proportion of participants with BOR of either CR or partial response (PR)	5 years
Secondary	Overall survival (OS)	OS: Time from randomization to date of death due to any cause	5 years
Secondary	Time to next anti-lymphoma treatment (TTNT)	TTNT: Time from randomization until start of new anticancer therapy or death due to any cause.	5 years
Secondary	Duration of Response (DOR)	Time from the date of first documented BIRC response of CR or PR to the date of first documented progression by BIRC or any cause of death	5 years
Secondary	Pre-existing (prior to treatment) and treatment-induced anti-mCAR antibodies (humoral immunogenicity)	Summarize percentage of patients with pre-existing and treatment-induced anti-mCAR antibodies, and relate the antibody responses with CAR expansion, efficacy, and safety endpoints.	5 years
Secondary	Anti-mCAR, T cell response, as measured by IFN? expression (cellular immunogenicity)	Summarize cellular immunogenicity by pre-infusion and post-infusion timepoints, and correlate cellular immunogenicity signals with CAR expansion, efficacy, and safety endpoints.	5 years
Secondary	CAR transgene levels, as measured by quantitative polymerase chain reaction (qPCR), in peripheral blood, bone marrow (and other tissues, if available)	Summary of transgene levels by timepoints and by clinical responses, cellular kinetic parameters will be derived using non-compartmental analysis from time course of transgene levels and will be summarized by clinical responses.	5 years
Secondary	Replication competent lentivirus (RCL) by VSV-g qPCR in participants receiving tisagenlecleucel	This is to assess presence of (Replication competent lentivirus) RCL in participants receiving tisagenlecleucel by VSV-g qPCR	5 years