Follicular Lymphoma
Conditions
Keywords
Refractory or relapsed Follicular Lymphoma, Refractory, Relapsed, Follicular lymphoma, CTL019, Tisagenlecleucel, Chimeric antigen receptor, CAR19, CAR-T
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.
Interventions
BIOLOGICALtisagenlecleucel
Tisagenlecleucel is single infusion.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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/
Countries
Australia, Austria, Belgium, France, Germany, Italy, Japan, Netherlands, Norway, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CTL019 All patients who received tisagenlecleucel infusion | 98 |
| Total | 98 |
Outcome results
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).
Time frame: 1 year
Population: Efficacy analysis set (EAS): All the patients who received tisagenlecleucel, and had measurable disease at baseline per IRC. Non-measurable disease at baseline is defined as absence of index lesion at baseline disease evaluation (i.e. no disease at baseline).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CTL019 | Complete Response Rate (CRR) Per Independent Review Committee (IRC) Assessment | 69.1 Percentage of participants |
Secondary
AUC0-28; Cellular Kinetic Parameter of Tisagenlecleucel
The AUC from time zero to day 28, in peripheral blood (%\*days or days\*copies/ µg)
Time frame: 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)
Time frame: 2 years
Secondary
Cellular Immunogenicity
Presence of T lymphocytes activated by the tisagenlecleucel protein
Time frame: 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)
Time frame: 2 years
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).
Time frame: 1 year
Secondary
Humoral Immunogenicity
Antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.
Time frame: 2 years
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).
Time frame: 1 year
Population: Efficacy analysis set (EAS): All the patients who received tisagenlecleucel, and had measurable disease at baseline per IRC. Non-measurable disease at baseline is defined as absence of index lesion at baseline disease evaluation (i.e. no disease at baseline).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CTL019 | Overall Response Rate (ORR) Per IRC Assessment | 86.2 Percentage or participants |
Secondary
Overall Survival (OS)
Time from tisagenlecleucel infusion to death due to any cause
Time frame: 2 years
Secondary
Progression Free Survival (PFS)
Time from tisagenlecleucel infusion to first documented disease progression or death due to any cause
Time frame: 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
Time frame: 2 years
Secondary
Summary Scores of PRO Measured by EQ-5D-3L Quality of Life Questionnaire
Effect of tisagenlecleucel therapy on Patient reported outcomes
Time frame: 2 years
Secondary
Summary Scores of PRO Measured by FACT-Lym Quality of Life Questionnaire
Effect of tisagenlecleucel therapy on Patient reported outcomes
Time frame: 2 years
Secondary
Summary Scores of PRO Measured by SF-36v2 Quality of Life Questionnaire
Effect of tisagenlecleucel therapy on Patient reported outcomes
Time frame: 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
Time frame: 2 years
Secondary
Tisagenlecleucel Transgene Concentration
Transgene concentration as detected by qPCR in target tissue
Time frame: 2 years
Secondary
Tlast; Cellular Kinetic Parameter of Tisagenlecleucel
The last observed measureable timepoint after dose administration
Time frame: 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)
Time frame: 2 years