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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Follicular Lymphoma

Intervention / Treatment
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* Biological: tisagenlecleucel


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CTL019<br>All patients who received tisagenlecleucel infusion. | Biological: tisagenlecleucel<br>* Tisagenlecleucel is single infusion.<br>* Other names: CTL019;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Progression Free Survival (PFS) | Time from tisagenlecleucel infusion to first documented disease progression or death due to any cause | 2 years | 
| Overall Survival (OS) | Time from tisagenlecleucel infusion to death due to any cause | 2 years | 
| Tisagenlecleucel Transgene Concentration | Transgene concentration as detected by qPCR in target tissue | 2 years | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Tlast; Cellular Kinetic Parameter of Tisagenlecleucel | The last observed measureable timepoint after dose administration | 2 years | 
| Summary of Exposure of CD3+ Tisagenlecleucel Cells in Peripheral Blood | In vivo cellular kinetics of CD3+ tisagenlecleucel cells detected by flow cytometry | 2 years | 
| Humoral Immunogenicity | Antibody titers specific to the tisagenlecleucel molecule prior to and following infusion. | 2 years | 
| Cellular Immunogenicity | Presence of T lymphocytes activated by the tisagenlecleucel protein | 2 years | 
| Summary Scores of PRO Measured by SF-36v2 Quality of Life Questionnaire | Effect of tisagenlecleucel therapy on Patient reported outcomes | 2 years | 
| Summary Scores of PRO Measured by EQ-5D-3L Quality of Life Questionnaire | Effect of tisagenlecleucel therapy on Patient reported outcomes | 2 years | 
| Summary Scores of PRO Measured by FACT-Lym Quality of Life Questionnaire | Effect of tisagenlecleucel therapy on Patient reported outcomes | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Refractory or relapsed Follicular Lymphoma, Refractory, Relapsed, Follicular lymphoma, CTL019, Tisagenlecleucel, Chimeric antigen receptor, CAR19, CAR-T