Back to resultsA Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma (LEDA)
Primary Purpose
Follicular Lymphoma (FL)
Status
Recruiting
Phase
Phase 3
Locations
Australia
Study Type
Interventional
Intervention
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)
Sponsored by
About this trial
This is an interventional treatment trial for Follicular Lymphoma (FL) focused on measuring relapsed or refractory follicular lymphoma, r/r, FL, CAR-T, tisagenlecleucel, CTL019, phase III, standard of care, SOC
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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
Sites / Locations
- Novartis Investigative SiteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Tisagenlecleucel
R2 or R-CHOP
Arm Description
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
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Complete response rate (CRR) as assessed by BIRC (Key Secondary)
CRR: The proportion of participants with BOR of complete response (CR)
Overall response rate (ORR) by BIRC
ORR: The proportion of participants with BOR of either CR or partial response (PR)
Overall survival (OS)
OS: Time from randomization to date of death due to any cause
Time to next anti-lymphoma treatment (TTNT)
TTNT: Time from randomization until start of new anticancer therapy or death due to any cause.
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
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.
Anti-mCAR, T cell response, as measured by IFNγ 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.
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05888493
Brief Title
A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2, 2023 (Actual)
Primary Completion Date
July 6, 2028 (Anticipated)
Study Completion Date
January 21, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma (FL)
Keywords
relapsed or refractory follicular lymphoma, r/r, FL, CAR-T, tisagenlecleucel, CTL019, phase III, standard of care, SOC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
108 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Tisagenlecleucel
Arm Type
Experimental
Arm Description
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
Arm Title
R2 or R-CHOP
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Tisagenlecleucel
Other Intervention Name(s)
CTL019
Intervention Description
Tisagenlecleucel is a solution for infusion of 0.6 to 6 x 10^8 CAR-positive viable T-cells taken intravenously (i.v.).
Intervention Type
Drug
Intervention Name(s)
Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles.
Other Intervention Name(s)
R2
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles
Other Intervention Name(s)
R-CHOP
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Lymphodepleting chemotherapy
Intervention Description
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)
Intervention Type
Other
Intervention Name(s)
Corticosteroids and/or Radiation (Bridging therapy)
Intervention Description
Corticosteroids and/or Radiation
Primary Outcome Measure Information:
Title
Progression-free survival (PFS) determined by blinded independent review committee (BIRC)
Description
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
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Complete response rate (CRR) as assessed by BIRC (Key Secondary)
Description
CRR: The proportion of participants with BOR of complete response (CR)
Time Frame
5 years
Title
Overall response rate (ORR) by BIRC
Description
ORR: The proportion of participants with BOR of either CR or partial response (PR)
Time Frame
5 years
Title
Overall survival (OS)
Description
OS: Time from randomization to date of death due to any cause
Time Frame
5 years
Title
Time to next anti-lymphoma treatment (TTNT)
Description
TTNT: Time from randomization until start of new anticancer therapy or death due to any cause.
Time Frame
5 years
Title
Duration of Response (DOR)
Description
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
Time Frame
5 years
Title
Pre-existing (prior to treatment) and treatment-induced anti-mCAR antibodies (humoral immunogenicity)
Description
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.
Time Frame
5 years
Title
Anti-mCAR, T cell response, as measured by IFNγ expression (cellular immunogenicity)
Description
Summarize cellular immunogenicity by pre-infusion and post-infusion timepoints, and correlate cellular immunogenicity signals with CAR expansion, efficacy, and safety endpoints.
Time Frame
5 years
Title
CAR transgene levels, as measured by quantitative polymerase chain reaction (qPCR), in peripheral blood, bone marrow (and other tissues, if available)
Description
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.
Time Frame
5 years
Title
Replication competent lentivirus (RCL) by VSV-g qPCR in participants receiving tisagenlecleucel
Description
This is to assess presence of (Replication competent lentivirus) RCL in participants receiving tisagenlecleucel by VSV-g qPCR
Time Frame
5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing URL
https://www.clinicalstudydatarequest.com
Learn more about this trial
A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma
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