NCT03568461 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2026-07-09

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

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Complete Response Rate (CRR) Per Independent Review Committee (IRC) Assessment

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outcome · POSTED

Overall Response Rate (ORR) Per IRC Assessment

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outcome · POSTED

Duration of Response (DOR) Per IRC Assessment

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outcome · POSTED

Duration of Response (DOR) for Complete Response (CR) Only Per IRC Assessment

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outcome · POSTED

Progression Free Survival (PFS) Per IRC Assessment

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Tisagenlecleucel Transgene Concentration Levels as Measured by Quantitative Polymerase Chain Reaction (qPCR) Method, by Clinical Response Per IRC Assessment

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outcome · POSTED

Cmax; Cellular Kinetic Parameter of Tisagenlecleucel Transgene Levels by qPCR, Based on Clinical Response IRC Assessment

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outcome · POSTED

Tmax; Cellular Kinetic Parameter of Tisagenlecleucel Transgene Levels by qPCR, Based on Clinical Response by IRC Assessment

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outcome · POSTED

AUC0-28d and AUC0-84d; Cellular Kinetic Parameter of Tisagenlecleucel Transgene Levels by qPCR, Based on Clinical Response by IRC Assessment

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outcome · POSTED

AUC0-28d and AUC0-84d; Cellular Kinetic Parameter for Tisagenlecleucel by Flow Cytometry, Based on Clinical Response by IRC Assessment

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outcome · POSTED

Cmax; Cellular Kinetic Parameter for Tisagenlecleucel by Flow Cytometry, Based on Clinical Response by IRC Assessment

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outcome · POSTED

Summary of Exposure of CD3+ Tisagenlecleucel Cells in Peripheral Blood for Tmax

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outcome · POSTED

Humoral Immunogenicity: Number of Participants With Anti-mCAR19 Antibodies, Per IRC Assessment

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outcome · POSTED

Cellular Immunogenicity: Percentage of Interferon Gamma (IFNg+) Cells by Flow Cytometry Per IRC Assessment

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outcome · POSTED

Summary Scores of Patient-reported Outcome (PRO) Measured by SF-36v2 Quality of Life Questionnaire by Visit

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outcome · POSTED

Summary Scores of PRO Measured by SF-36v2 Quality of Life Questionnaire Reported by Change From Baseline

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outcome · POSTED

Health Status Measured by EQ-5D-3L Questionnaire

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outcome · POSTED

Summary Scores of PRO Measured by EQ-VAS Quality of Life Questionnaire by Visit

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outcome · POSTED

Summary Scores of PRO Measured by EQ-VAS Quality of Life Questionnaire Reported by Change From Baseline

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outcome · POSTED

Summary Scores of PRO Measured by FACT-Lym Quality of Life Questionnaire

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outcome · POSTED

Summary Scores of PRO Measured by FACT-Lym Quality of Life Questionnaire Reported by Change From Baseline

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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.
healthy Volunteers: false
maximum Age: 100 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
All patients who received tisagenlecleucel infusion.
intervention Names
Biological: tisagenlecleucel
label
CTL019
type
EXPERIMENTAL

interventions

arm Group Labels
CTL019
description
Tisagenlecleucel is single infusion.
name
tisagenlecleucel
other Names
CTL019
type
BIOLOGICAL

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 98
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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).
measure
Complete Response Rate (CRR) Per Independent Review Committee (IRC) Assessment
time Frame
1 year

secondary Outcomes

description
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).
measure
Overall Response Rate (ORR) Per IRC Assessment
time Frame
1 year
description
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). DOR was estimated using the Kaplan-Meier method.
measure
Duration of Response (DOR) Per IRC Assessment
time Frame
approx. 60 months
description
Duration of response (DOR) applied only to participants whose best overall disease response was complete response (CR) only. It is defined as the time from the date of first documented disease response (CR only) to the date of first documented progression or death due to follicular lymphoma (FL). DOR was estimated using the Kaplan-Meier method.
measure
Duration of Response (DOR) for Complete Response (CR) Only Per IRC Assessment
time Frame
approx. 60 months
description
Progression free survival is the time from tisagenlecleucel infusion to first documented disease progression or death due to any cause. PFS was estimated using the Kaplan-Meier method.
measure
Progression Free Survival (PFS) Per IRC Assessment
time Frame
up to 61.7 months
description
Overall Survival is the time from tisagenlecleucel infusion to death due to any cause. OS was estimated using the Kaplan-Meier method.
measure
Overall Survival (OS)
time Frame
up to 65.8 months
description
This is the summary of cellular kinetic concentrations for tisagenlecleucel (CTL019) transgene levels in peripheral blood and bone marrow following infusion.
measure
Tisagenlecleucel Transgene Concentration Levels as Measured by Quantitative Polymerase Chain Reaction (qPCR) Method, by Clinical Response Per IRC Assessment
time Frame
Month 60 (peripheral blood), Month 6 (bone marrow)
description
Cmax is the maximum (peak) observed in peripheral blood after single dose administration. Actual sampling times were taken into consideration for the calculation of cellular kinetic parameters parameters.
measure
Cmax; Cellular Kinetic Parameter of Tisagenlecleucel Transgene Levels by qPCR, Based on Clinical Response IRC Assessment
time Frame
up to 60 months after infusion
description
Tmax is the time to reach maximum (peak) peripheral blood after single dose administration (days). Actual sampling times were taken into consideration for the calculation of cellular kinetic parameters.
measure
Tmax; Cellular Kinetic Parameter of Tisagenlecleucel Transgene Levels by qPCR, Based on Clinical Response by IRC Assessment
time Frame
up to 60 months after infusion
description
AUC0-28 is the area under curve (AUC) from time zero to day 28 in peripheral blood. AUC0-84d is the AUC from time zero to day 84 in peripheral blood. Actual sampling times were taken into consideration for the calculation of cellular kinetic parameters.
measure
AUC0-28d and AUC0-84d; Cellular Kinetic Parameter of Tisagenlecleucel Transgene Levels by qPCR, Based on Clinical Response by IRC Assessment
time Frame
0 to 28 days after infusion, 0 to 84 days after infusion
description
Exposure is summarized as area under the curve (AUC) from time 0 to 28 days (AUC0-28d) and from time to 84 days (AUC0-84d). The cellular kinetic parameters were estimated from the percentages of CD3+/CTL019+ cells obtained from flow cytometry. Flow cytometry measures the surface expression of chimeric antigen receptors (CARs) on T cells.
measure
AUC0-28d and AUC0-84d; Cellular Kinetic Parameter for Tisagenlecleucel by Flow Cytometry, Based on Clinical Response by IRC Assessment
time Frame
AUC0-28d: from time of infusion to 28 days post-dose; AUC0-84d: from time of infusion to 84 days post-infusion
description
Cmax is the maximum (peak) observed in peripheral blood after single dose administration. Actual sampling times were taken into consideration for the calculation of cellular kinetic parameters parameters.
measure
Cmax; Cellular Kinetic Parameter for Tisagenlecleucel by Flow Cytometry, Based on Clinical Response by IRC Assessment
time Frame
From pre-dose until 60 months after infusion
description
In vivo cellular kinetics of CD3+/CTL019+ levels tisagenlecleucel cells detected by flow cytometry base on best overall response (BOR). The cellular kinetic parameters were estimated from the percentages of CD3+/CTL019+ cells obtained from flow cytometry. Flow cytometry measures the surface expression of chimeric antigen receptors (CARs) on T cells.
measure
Summary of Exposure of CD3+ Tisagenlecleucel Cells in Peripheral Blood for Tmax
time Frame
From pre-dose until 60 months after infusion

Full study description

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.

Source references

references

citation
Dreyling M, Fowler NH, Dickinson 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, Maria Ferreri AJ, Teshima T, Patten PEM, McGuirk JP, Petzer AL, Offner F, Viardot A, Zinzani PL, Malladi R, Paule I, Zia A, Awasthi R, Han X, Germano D, O'Donovan D, Ramos R, Maier HJ, Masood A, Thieblemont C, Schuster SJ. Durable response after tisagenlecleucel in adults with relapsed/refractory follicular lymphoma: ELARA trial update. Blood. 2024 Apr 25;143(17):1713-1725. doi: 10.1182/blood.2023021567.
pmid
38194692
type
DERIVED
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.
pmid
35973192
type
DERIVED
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.
pmid
34921238
type
DERIVED