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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05888493




Registration number
NCT05888493
Ethics application status
Date submitted
1/05/2023
Date registered
5/06/2023

Titles & IDs
Public title
A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma
Scientific 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)
Secondary ID [1] 0 0
2023-503452-27-00
Secondary ID [2] 0 0
CCTL019E2301
Universal Trial Number (UTN)
Trial acronym
LEDA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Follicular Lymphoma (FL) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Tisagenlecleucel
Treatment: Drugs - Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles.
Treatment: Drugs - Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles
Treatment: Drugs - Lymphodepleting chemotherapy
Other interventions - Corticosteroids and/or Radiation (Bridging therapy)

Experimental: Tisagenlecleucel - 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

Active comparator: R2 or R-CHOP - 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.


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

Treatment: Drugs: 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

Treatment: Drugs: 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

Treatment: Drugs: 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 interventions: Corticosteroids and/or Radiation (Bridging therapy)
Corticosteroids and/or Radiation
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS) determined by blinded independent review committee (BIRC)
Timepoint [1] 0 0
5 years
Secondary outcome [1] 0 0
Complete response rate (CRR) as assessed by BIRC (Key Secondary)
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Overall response rate (ORR) by BIRC
Timepoint [2] 0 0
5 years
Secondary outcome [3] 0 0
Overall survival (OS)
Timepoint [3] 0 0
5 years
Secondary outcome [4] 0 0
Time to next anti-lymphoma treatment (TTNT)
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
Duration of Response (DOR)
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
Pre-existing (prior to treatment) and treatment-induced anti-mCAR antibodies (humoral immunogenicity)
Timepoint [6] 0 0
5 years
Secondary outcome [7] 0 0
Anti-mCAR, T cell response, as measured by IFN? expression (cellular immunogenicity)
Timepoint [7] 0 0
5 years
Secondary outcome [8] 0 0
CAR transgene levels, as measured by quantitative polymerase chain reaction (qPCR), in peripheral blood, bone marrow (and other tissues, if available)
Timepoint [8] 0 0
5 years
Secondary outcome [9] 0 0
Replication competent lentivirus (RCL) by VSV-g qPCR in participants receiving tisagenlecleucel
Timepoint [9] 0 0
5 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
7/02/2029
Actual
Sample size
Target
108
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Clayton
Recruitment hospital [2] 0 0
Novartis Investigative Site - Melbourne
Recruitment hospital [3] 0 0
Novartis Investigative Site - Nedlands
Recruitment hospital [4] 0 0
Novartis Investigative Site - Camperdown
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment postcode(s) [4] 0 0
NSW - Camperdown
Recruitment outside Australia
Country [1] 0 0
Czechia
State/province [1] 0 0
Poruba
Country [2] 0 0
Hungary
State/province [2] 0 0
Budapest
Country [3] 0 0
Korea, Republic of
State/province [3] 0 0
Seoul
Country [4] 0 0
Poland
State/province [4] 0 0
Slaskie
Country [5] 0 0
Poland
State/province [5] 0 0
Wielkopolskie
Country [6] 0 0
Poland
State/province [6] 0 0
Gdansk
Country [7] 0 0
Poland
State/province [7] 0 0
Lodz
Country [8] 0 0
Romania
State/province [8] 0 0
Bucharest
Country [9] 0 0
Singapore
State/province [9] 0 0
Singapore
Country [10] 0 0
Slovakia
State/province [10] 0 0
Slovak Republic
Country [11] 0 0
Spain
State/province [11] 0 0
Cantabria
Country [12] 0 0
Spain
State/province [12] 0 0
Castilla Y Leon
Country [13] 0 0
Spain
State/province [13] 0 0
Catalunya
Country [14] 0 0
Spain
State/province [14] 0 0
Murcia
Country [15] 0 0
Spain
State/province [15] 0 0
Barcelona
Country [16] 0 0
Spain
State/province [16] 0 0
Madrid
Country [17] 0 0
Taiwan
State/province [17] 0 0
Taichung
Country [18] 0 0
Taiwan
State/province [18] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.clinicalstudydatarequest.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05888493