Trial Title:
A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma
NCT ID:
NCT05888493
Condition:
Follicular Lymphoma (FL)
Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Prednisone
Prednisolone
Cyclophosphamide
Rituximab
Doxorubicin
Vincristine
Lenalidomide
Tisagenlecleucel
Conditions: Keywords:
relapsed or refractory follicular lymphoma
r/r
FL
CAR-T
tisagenlecleucel
CTL019
phase III
standard of care
SOC
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Tisagenlecleucel
Description:
Tisagenlecleucel is a solution for infusion of 0.6 to 6 x 10^8 CAR-positive viable
T-cells taken intravenously (i.v.).
Arm group label:
Tisagenlecleucel
Other name:
CTL019
Intervention type:
Drug
Intervention name:
Lenalidomide and rituximab (R2) in 28-day cycles for up to 12 cycles.
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
Arm group label:
R2 or R-CHOP
Other name:
R2
Intervention type:
Drug
Intervention name:
Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone or prednisolone (R-CHOP) in 21-day cycles for 6 to 8 cycles
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
Arm group label:
R2 or R-CHOP
Other name:
R-CHOP
Intervention type:
Drug
Intervention name:
Lymphodepleting chemotherapy
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)
Arm group label:
Tisagenlecleucel
Intervention type:
Other
Intervention name:
Corticosteroids and/or Radiation (Bridging therapy)
Description:
Corticosteroids and/or Radiation
Arm group label:
Tisagenlecleucel
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.
Criteria for eligibility:
Criteria:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Novartis Investigative Site
Address:
City:
Clayton
Zip:
3168
Country:
Australia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Melbourne
Zip:
3004
Country:
Australia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Nedlands
Zip:
6009
Country:
Australia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Camperdown
Zip:
NSW
Country:
Australia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Ostrava
Zip:
708 52
Country:
Czechia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Budapest
Zip:
H-1097
Country:
Hungary
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Seoul
Zip:
03080
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Seoul
Zip:
03722
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Seoul
Zip:
05505
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Seoul
Zip:
06351
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Seoul
Zip:
06591
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Gliwice
Zip:
44-101
Country:
Poland
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Poznan
Zip:
60-569
Country:
Poland
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Gdansk
Zip:
80-952
Country:
Poland
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Lodz
Zip:
93 513
Country:
Poland
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Bucharest
Zip:
022328
Country:
Romania
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Singapore
Zip:
119074
Country:
Singapore
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Bratislava
Zip:
83310
Country:
Slovakia
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Cordoba
Zip:
14004
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Santander
Zip:
39008
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Salamanca
Zip:
37007
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Barcelona
Zip:
08035
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Hospitalet de LLobregat
Zip:
08907
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
El Palmar
Zip:
30120
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Barcelona
Zip:
08041
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Taichung
Zip:
407219
Country:
Taiwan
Status:
Recruiting
Facility:
Name:
Novartis Investigative Site
Address:
City:
Taipei
Zip:
10002
Country:
Taiwan
Status:
Recruiting
Start date:
October 2, 2023
Completion date:
January 18, 2031
Lead sponsor:
Agency:
Novartis Pharmaceuticals
Agency class:
Industry
Source:
Novartis
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05888493
