Follicular Lymphoma (FL)Phase 3LEDANCT05888493
A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma
A Phase 3 study testing Tisagenlecleucel, Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles. and Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles in people with Follicular Lymphoma (FL), run by Novartis Pharmaceuticals at 30 sites in 11 countries.
Trial summary
This trial will compare tisagenlecleucel to standard of care in adult participants with relapsed or refractory (r/r) follicular lymphoma. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Follicular Lymphoma (FL)
- What is being tested?
- Tisagenlecleucel, Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles. and Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 109 participants
- Where
- 30 sitesin 11 countries
- Study dates
- 2 Oct 2023to 20 Feb 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years at the date of signing the informed consent form.
- Follicular lymphoma grade 1, 2, or 3A confirmed histologically after latest relapse (local assessment).
- Relapsed or refractory disease after a second or later line of systemic therapy including an anti-CD20 antibody and an alkylating agent.
- 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.
- ECOG performance status of 0, 1 or 2 at screening.
- Adequate hematologic, renal, hepatic and pulmonary organ function at screening.
- Must meet the institutional criteria to undergo leukapheresis (unless historical leukapheresis is available).
- Must be eligible for treatment with the selected standard of care regimen.
Who cannot join
- Follicular lymphoma grade 3B or evidence of histologic transformation.
- Prior treatment with anti-CD19 therapy, gene therapy, or adoptive T-cell therapy.
- Active CNS involvement by malignancy.
- Clinically significant active infection, presence of Human immunodeficiency virus (HIV) antibody or active hepatitis B or C.
- Active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré syndrome).
- Investigational medicinal product within the last 30 days or five half-lives (whichever is longer) prior to randomization.
- 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
Trial locations and contacts
30 sites in 11 countries.
30 sites in 11 countries
Spain8 sites
Novartis Investigative Site
Barcelona, 08035
Novartis Investigative Site
Córdoba, 14004
Novartis Investigative Site
El Palmar, Murcia, 30120
Novartis Investigative Site
L'Hospitalet de Llobregat, Barcelona, 08907
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Salamanca, 37007
Novartis Investigative Site
Santander, Cantabria, 39008
Novartis Investigative Site
Santiago Compostela, A Coruna, 15706
South Korea5 sites
Novartis Investigative Site
Seoul, 03080
Novartis Investigative Site
Seoul, 03722
Novartis Investigative Site
Seoul, 05505
Novartis Investigative Site
Seoul, 06351
Novartis Investigative Site
Seoul, 06591
Australia4 sites
Novartis Investigative Site
Camperdown, New South Wales, 2050
Novartis Investigative Site
Clayton, Victoria, 3168
Novartis Investigative Site
Melbourne, Victoria, 3004
Novartis Investigative Site
Nedlands, Western Australia, 6009
Poland4 sites
Novartis Investigative Site
Gdansk, 80-952
Novartis Investigative Site
Gliwice, Silesian Voivodeship, 44-101
Novartis Investigative Site
Lodz, 93-513
Novartis Investigative Site
Poznan, Greater Poland Voivodeship, 60-355
Taiwan3 sites
Novartis Investigative Site
Kaohsiung City, 83301
Novartis Investigative Site
Taichung, 407219
Novartis Investigative Site
Taipei, 10002
About this study
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)
This trial will compare tisagenlecleucel to standard of care in adult participants with relapsed or refractory (r/r) follicular lymphoma.
Read the detailed 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.
- Conditions
- Follicular Lymphoma (FL)
- Being tested
- Tisagenlecleucel, Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles., Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles, Lymphodepleting chemotherapy, Corticosteroids and/or Radiation (Bridging therapy)
- Keywords
- relapsed or refractory follicular lymphoma, r/r, FL, CAR-T, tisagenlecleucel, CTL019, phase III, standard of care, SOC
- Medical subject headings
- Lymphoma, Follicular, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TisagenlecleucelBiological
Also called CTL019
Tisagenlecleucel is a solution for infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells taken intravenously (i.v.).
Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles.Drug
Also called R2
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 cyclesDrug
Also called R-CHOP
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 chemotherapyDrug
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)
Corticosteroids and/or Radiation (Bridging therapy)Other
Corticosteroids and/or Radiation
| Study group | Role | What they receive |
|---|---|---|
| Tisagenlecleucel | Experimental | 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 Receives: Biological: Tisagenlecleucel; Drug: Lymphodepleting chemotherapy; Other: Corticosteroids and/or Radiation (Bridging therapy) |
| R2 or R-CHOP | Active comparator | 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. Receives: Drug: Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles.; Drug: Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 5 years
Secondary outcomes (8)
Complete response rate (CRR) as assessed by BIRC (Key Secondary)
CRR: The proportion of participants with BOR of complete response (CR)
Measured: 5 years
Overall response rate (ORR) by BIRC
ORR: The proportion of participants with BOR of either CR or partial response (PR)
Measured: 5 years
Overall survival (OS)
OS: Time from randomization to date of death due to any cause
Measured: 5 years
Time to next anti-lymphoma treatment (TTNT)
TTNT: Time from randomization until start of new anticancer therapy or death due to any cause.
Measured: 5 years
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
Measured: 5 years
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.
Measured: 5 years
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.
Measured: 5 years
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
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2023
- Study start2 Oct 2023
- Primary completion25 Jul 2028 (estimated)
- Study completion20 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Follicular Lymphoma (FL)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05888493
- Sponsor's protocol ID
- CCTL019E2301
- Other IDs
- 2023-503452-27-00, 2023
- Acronym
- LEDA
- Status last verified
- Apr 2026
- First submitted
- 1 May 2023
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT05888493
- Acronym / sponsor ID
- LEDA / CCTL019E2301
- Conditions
- Follicular Lymphoma (FL)
- Keywords
- relapsed or refractory follicular lymphoma, r/r, FL, CAR-T, tisagenlecleucel, CTL019, phase III, standard of care
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 109 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 2 Oct 2023 (actual)
- Primary completion
- 25 Jul 2028 (estimated)
- Study completion
- 20 Feb 2031 (estimated)
- First posted
- 5 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial will compare tisagenlecleucel to standard of care in adult participants with relapsed or refractory (r/r) follicular lymphoma.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tisagenlecleucel | Experimental | Biological: Tisagenlecleucel, Drug: Lymphodepleting chemotherapy, Other: Corticosteroids and/or Radiation (Bridging therapy)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 |
| R2 or R-CHOP | Active comparator | Drug: Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles., Drug: Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cyclesParticipants 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years at the date of signing the informed consent form.
- Follicular lymphoma grade 1, 2, or 3A confirmed histologically after latest relapse (local assessment).
- Relapsed or refractory disease after a second or later line of systemic therapy including an anti-CD20 antibody and an alkylating agent.
- 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.
- ECOG performance status of 0, 1 or 2 at screening.
Key exclusion criteria (8 listed)
- Follicular lymphoma grade 3B or evidence of histologic transformation.
- Prior treatment with anti-CD19 therapy, gene therapy, or adoptive T-cell therapy.
- Active CNS involvement by malignancy.
- Clinically significant active infection, presence of Human immunodeficiency virus (HIV) antibody or active hepatitis B or C.
- Active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré syndrome).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TisagenlecleucelAlso: CTL019Tisagenlecleucel is a solution for infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells taken intravenously (i.v.). | Biological | Tisagenlecleucel |
| Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles.Also: R2Lenalidomide 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 | Drug | R2 or R-CHOP |
| Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cyclesAlso: R-CHOPRituximab 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 | Drug | R2 or R-CHOP |
| Lymphodepleting chemotherapyFludarabine (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) | Drug | Tisagenlecleucel |
| Corticosteroids and/or Radiation (Bridging therapy)Corticosteroids and/or Radiation | Other | Tisagenlecleucel |
Primary outcome
Progression-free survival (PFS) determined by blinded independent review committee (BIRC)
Time frame: 5 years
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
8 secondary outcomes
Complete response rate (CRR) as assessed by BIRC (Key Secondary)
Time frame: 5 years
Overall response rate (ORR) by BIRC
Time frame: 5 years
Overall survival (OS)
Time frame: 5 years
Time to next anti-lymphoma treatment (TTNT)
Time frame: 5 years
Duration of Response (DOR)
Time frame: 5 years
Pre-existing (prior to treatment) and treatment-induced anti-mCAR antibodies (humoral immunogenicity)
Time frame: 5 years
CAR transgene levels, as measured by quantitative polymerase chain reaction (qPCR), in peripheral blood, bone marrow (and other tissues, if available)
Time frame: 5 years
Replication competent lentivirus (RCL) by VSV-g qPCR in participants receiving tisagenlecleucel
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2026.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
30 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tisagenlecleucel, Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles. and Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles in people with Follicular Lymphoma (FL), run by Novartis Pharmaceuticals at 30 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Spain, South Korea, Australia, Poland, Taiwan and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) determined by blinded independent review committee (BIRC) (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.