Efficacy and Safety of Tisagenlecleucel in Adult Patients With Refractory or Relapsed Follicular Lymphoma

Follicular Lymphoma Clinical Trial

— ELARA  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03568461
• Other study ID #: CCTL019E2202
• Secondary ID: 2017-004385-94
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 12, 2018
• Est. completion date: May 22, 2025

Study information

• Verified date: November 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 98
• Est. completion date: May 22, 2025
• Est. primary completion date: November 24, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Follicular Lymphoma
• Lymphoma
• Lymphoma, Follicular

Intervention

Biological:
• tisagenlecleucel
Tisagenlecleucel is single infusion.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Camperdown
Australia	Novartis Investigative Site	Herston	Queensland
Australia	Novartis Investigative Site	Melbourne	Victoria
Austria	Novartis Investigative Site	Linz
Belgium	Novartis Investigative Site	Gent
France	Novartis Investigative Site	Paris 10
France	Novartis Investigative Site	Pierre Benite
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Ulm
Italy	Novartis Investigative Site	Bologna	BO
Italy	Novartis Investigative Site	Milano	MI
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Sapporo city	Hokkaido
Japan	Novartis Investigative Site	Sendai city	Miyagi
Netherlands	Amsterdam UMC, locatie AMC	Amsterdam
Norway	Novartis Investigative Site	Oslo
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Sevilla	Andalucia
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	London
United States	Michigan Med University of Michigan	Ann Arbor	Michigan
United States	University of Chicago Medical Center Hematology and Oncology	Chicago	Illinois
United States	City of Hope National Medical Center Dept.ofCityofHopeMedicalCtr(1)	Duarte	California
United States	MD Anderson Cancer Center SC	Houston	Texas
United States	University of Kansas Hospital and Medical Center DeptofUofKansas CancerCenter-2	Kansas City	Kansas
United States	University of Pennsylvania Clinical Perelman Center for Adv Med	Philadelphia	Pennsylvania
United States	Oregon Health Sciences University .	Portland	Oregon
United States	UCSF Medical Center .	San Francisco	California
United States	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  France,  Germany,  Italy,  Japan,  Netherlands,  Norway,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Response Rate (CRR) Per Independent Review Committee (IRC) Assessment	Complete response rate was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) recorded from tisagenlecleucel infusion until progressive disease or start of new anticancer therapy, whichever came first. CRR was determined by an independent review committee (IRC) and was based on Lugano 2014 classification response criteria. The radiological response is first obtained from CT and PET studies according to the Lugano 2014 criteria. CT response is based on anatomical measurements of index/non-index/new lesions and spleen length. The possible response outcomes are complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). PET response based on a 5-point scale (5PS) or Deauville score. The possible outcomes for PET response are complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD).	1 year
Secondary	Overall Response Rate (ORR) Per IRC Assessment	Overall response rate is defined as the percentage of participants with a best overall disease response of complete response (CR) or partial response (PR). Response was evaluated per Lugano 2014 classification response criteria. The radiological response is first obtained from CT and PET studies according to the Lugano 2014 criteria. CT response is based on anatomical measurements of index/non-index/new lesions and spleen length. The possible response outcomes are complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). PET response based on a 5-point scale (5PS) or Deauville score. The possible outcomes for PET response are complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (NMR), or progressive metabolic disease (PMD).	1 year
Secondary	Duration of Response (DOR) Per IRC	Duration of response (DOR) applied only to participants whose best overall disease response was CR or PR. It is defined as the time from the date of first documented disease response (CR or PR) to the date of first documented progression or death due to follicular lymphoma (FL).	1 year
Secondary	Progression Free Survival (PFS)	Time from tisagenlecleucel infusion to first documented disease progression or death due to any cause	2 years
Secondary	Overall Survival (OS)	Time from tisagenlecleucel infusion to death due to any cause	2 years
Secondary	Tisagenlecleucel Transgene Concentration	Transgene concentration as detected by qPCR in target tissue	2 years
Secondary	Cmax; Cellular Kinetic Parameter of Tisagenlecleucel	The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (% or copies/ µg)	2 years
Secondary	Tmax; Cellular Kinetic Parameter of Tisagenlecleucel	The time to reach maximum (peak) peripheral blood or other body fluid drug concentration after single dose administration (days)	2 years
Secondary	AUC0-28; Cellular Kinetic Parameter of Tisagenlecleucel	The AUC from time zero to day 28, in peripheral blood (%*days or days*copies/ µg)	2 years
Secondary	AUC0-84d; Cellular Kinetic Parameter of Tisagenlecleucel	The AUC from time zero to day 84, in peripheral blood (%*days or days*copies/ µg)	2 years
Secondary	T1/2; Cellular Kinetic Parameter of Tisagenlecleucel	The half-life associated with the elimination phase slope of a semi logarithmic concentration-time curve (days) in peripheral blood	2 years
Secondary	Tlast; Cellular Kinetic Parameter of Tisagenlecleucel	The last observed measureable timepoint after dose administration	2 years
Secondary	Summary of Exposure of CD3+ Tisagenlecleucel Cells in Peripheral Blood	In vivo cellular kinetics of CD3+ tisagenlecleucel cells detected by flow cytometry	2 years
Secondary	Humoral Immunogenicity	Antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.	2 years
Secondary	Cellular Immunogenicity	Presence of T lymphocytes activated by the tisagenlecleucel protein	2 years
Secondary	Summary Scores of PRO Measured by SF-36v2 Quality of Life Questionnaire	Effect of tisagenlecleucel therapy on Patient reported outcomes	2 years
Secondary	Summary Scores of PRO Measured by EQ-5D-3L Quality of Life Questionnaire	Effect of tisagenlecleucel therapy on Patient reported outcomes	2 years
Secondary	Summary Scores of PRO Measured by FACT-Lym Quality of Life Questionnaire	Effect of tisagenlecleucel therapy on Patient reported outcomes	2 years