Clinical trial NCT05888493: A Phase III Trial Comparing Tisagenlecleucel to Standard of Care (SoC) in Adult Participants With r/r Follicular Lymphoma
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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Follicular Lymphoma (FL)
Keywords: relapsed or refractory follicular lymphoma
r/r
FL
CAR-T
tisagenlecleucel
CTL019
phase III
standard of care
SOC
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-06-05
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-free survival (PFS) determined by blinded independent review committee (BIRC)
timeFrame: 5 years
Secondary outcomes:
measure: Complete response rate (CRR) as assessed by BIRC (Key Secondary)
timeFrame: 5 years
measure: Overall response rate (ORR) by BIRC
timeFrame: 5 years
measure: Overall survival (OS)
timeFrame: 5 years
measure: Time to next anti-lymphoma treatment (TTNT)
timeFrame: 5 years
measure: Duration of Response (DOR)
timeFrame: 5 years
measure: Pre-existing (prior to treatment) and treatment-induced anti-mCAR antibodies (humoral immunogenicity)
timeFrame: 5 years
measure: Anti-mCAR, T cell response, as measured by IFNγ expression (cellular immunogenicity)
timeFrame: 5 years
measure: CAR transgene levels, as measured by quantitative polymerase chain reaction (qPCR), in peripheral blood, bone marrow (and other tissues, if available)
timeFrame: 5 years
measure: Replication competent lentivirus (RCL) by VSV-g qPCR in participants receiving tisagenlecleucel
timeFrame: 5 years
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: TRIHEALTH Good Samarithan Hospital
state: Ohio
city: Camperdown
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Clayton
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Ostrava
country: Czechia
facility: Novartis Investigative Site
state: Poruba
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Gliwice
country: Poland
facility: Novartis Investigative Site
state: Slaskie
city: Poznan
country: Poland
facility: Novartis Investigative Site
state: Wielkopolskie
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Bucharest
country: Romania
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
state: Slovak Republic
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Santander
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: El Palmar
country: Spain
facility: Novartis Investigative Site
state: Murcia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: