Clinical trial NCT03568461: Efficacy and Safety of Tisagenlecleucel in Adult Patients With Refractory or Relapsed Follicular Lymphoma
Official title: A Phase II, Single Arm, Multicenter Open Label Trial to Determine the Efficacy and Safety of Tisagenlecleucel (CTL019) in Adult Patients With Refractory or Relapsed Follicular Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Follicular Lymphoma
Keywords: Refractory or relapsed Follicular Lymphoma
Refractory
Relapsed
Follicular lymphoma
CTL019
Tisagenlecleucel
Chimeric antigen receptor
CAR19
CAR-T
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-06-26
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multi-center, phase II study to determine the efficacy and safety of tisagenlecleucel in adult patients with relapsed or refractory FL.

Detailed description: This single-arm, open label study had the following sequential phases: Screening, Pretreatment, Treatment and Follow-up. In the Pre-treatment phase, the patient could undergo bridging therapy (optional) and lymphodepleting (LD) chemotherapy. Treatment and Follow-up Phase included tisagenlecleucel infusion, and safety and efficacy follow-up for at least 24 months. For all the patients who received tisagenlecleucel infusion, additional survival follow-up was to be performed to determine survival status every 3 months.

Eligibility criteria: Inclusion Criteria:

* Refractory or relapsed Follicular Lymphoma (Grade 1, 2, 3A)
* Radiographically measurable disease at screening

Exclusion Criteria:

* Evidence of histologic transformation
* Follicular Lymphoma Grade 3B
* Prior anti-CD19 therapy
* Prior gene therapy
* Prior adoptive T cell therapy
* Prior allogeneic hematopoietic stem cell transplant
* Active CNS involvement by malignancy

Other protocol-defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Complete Response Rate (CRR) Per Independent Review Committee (IRC) Assessment
timeFrame: 1 year
Secondary outcomes:
measure: Overall Response Rate (ORR) Per IRC Assessment
timeFrame: 1 year
measure: Duration of Response (DOR) Per IRC
timeFrame: 1 year
measure: Progression Free Survival (PFS)
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Tisagenlecleucel Transgene Concentration
timeFrame: 2 years
measure: Cmax; Cellular Kinetic Parameter of Tisagenlecleucel
timeFrame: 2 years
measure: Tmax; Cellular Kinetic Parameter of Tisagenlecleucel
timeFrame: 2 years
measure: AUC0-28; Cellular Kinetic Parameter of Tisagenlecleucel
timeFrame: 2 years
measure: AUC0-84d; Cellular Kinetic Parameter of Tisagenlecleucel
timeFrame: 2 years
measure: T1/2; Cellular Kinetic Parameter of Tisagenlecleucel
timeFrame: 2 years
measure: Tlast; Cellular Kinetic Parameter of Tisagenlecleucel
timeFrame: 2 years
measure: Summary of Exposure of CD3+ Tisagenlecleucel Cells in Peripheral Blood
timeFrame: 2 years
measure: Humoral Immunogenicity
timeFrame: 2 years
measure: Cellular Immunogenicity
timeFrame: 2 years
measure: Summary Scores of PRO Measured by SF-36v2 Quality of Life Questionnaire
timeFrame: 2 years
measure: Summary Scores of PRO Measured by EQ-5D-3L Quality of Life Questionnaire
timeFrame: 2 years
measure: Summary Scores of PRO Measured by FACT-Lym Quality of Life Questionnaire
timeFrame: 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Chicago
country: United States
facility: Uni of Chi Medi Ctr Hema and Onco
state: Illinois
city: Kansas City
country: United States
facility: Univ of Kansas Hosp and Med Ctr
state: Kansas
city: Ann Arbor
country: United States
facility: Michigan Med University of Michigan
state: Michigan
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Clinical
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Camperdown
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Herston
country: Australia
facility: Novartis Investigative Site
city: Linz
country: Austria
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Paris 10
country: France
facility: Novartis Investigative Site
city: Pierre Benite
country: France
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sendai city
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, locatie AMC
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Salles G, Schuster SJ, Dreyling M, Fischer L, Kuruvilla J, Patten PEM, von Tresckow B, Smith SM, Jimenez-Ubieto A, Davis KL, Anjos C, Chu J, Zhang J, Lobetti Bodoni C, Thieblemont C, Fowler NH, Dickinson M, Martinez-Lopez J, Wang Y, Link BK. Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma. Blood Adv. 2022 Nov 22;6(22):5835-5843. doi: 10.1182/bloodadvances.2022008150.
citation: Fowler NH, Dickinson M, Dreyling M, Martinez-Lopez J, Kolstad A, Butler J, Ghosh M, Popplewell L, Chavez JC, Bachy E, Kato K, Harigae H, Kersten MJ, Andreadis C, Riedell PA, Ho PJ, Perez-Simon JA, Chen AI, Nastoupil LJ, von Tresckow B, Ferreri AJM, Teshima T, Patten PEM, McGuirk JP, Petzer AL, Offner F, Viardot A, Zinzani PL, Malladi R, Zia A, Awasthi R, Masood A, Anak O, Schuster SJ, Thieblemont C. Tisagenlecleucel in adult relapsed or refractory follicular lymphoma: the phase 2 ELARA trial. Nat Med. 2022 Feb;28(2):325-332. doi: 10.1038/s41591-021-01622-0. Epub 2021 Dec 17.