Efficacy and Safety of Tisagenlecleucel in Adult Patients With Refractory or Relapsed Follicular Lymphoma
- Registration Number
- NCT03568461
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 98
- Refractory or relapsed Follicular Lymphoma (Grade 1, 2, 3A)
- Radiographically measurable disease at screening
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CTL019 tisagenlecleucel All patients who received tisagenlecleucel infusion.
- Primary Outcome Measures
Name Time Method Complete Response Rate (CRR) Per Independent Review Committee (IRC) Assessment 1 year 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).
- Secondary Outcome Measures
Name Time Method Humoral Immunogenicity 2 years Antibody titers specific to the tisagenlecleucel molecule prior to and following infusion.
AUC0-84d; Cellular Kinetic Parameter of Tisagenlecleucel 2 years The AUC from time zero to day 84, in peripheral blood (%\*days or days\*copies/ µg)
Overall Response Rate (ORR) Per IRC Assessment 1 year 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).
Tisagenlecleucel Transgene Concentration 2 years Transgene concentration as detected by qPCR in target tissue
Tmax; Cellular Kinetic Parameter of Tisagenlecleucel 2 years The time to reach maximum (peak) peripheral blood or other body fluid drug concentration after single dose administration (days)
T1/2; Cellular Kinetic Parameter of Tisagenlecleucel 2 years The half-life associated with the elimination phase slope of a semi logarithmic concentration-time curve (days) in peripheral blood
Summary Scores of PRO Measured by FACT-Lym Quality of Life Questionnaire 2 years Effect of tisagenlecleucel therapy on Patient reported outcomes
Tlast; Cellular Kinetic Parameter of Tisagenlecleucel 2 years The last observed measureable timepoint after dose administration
Progression Free Survival (PFS) 2 years Time from tisagenlecleucel infusion to first documented disease progression or death due to any cause
Summary Scores of PRO Measured by EQ-5D-3L Quality of Life Questionnaire 2 years Effect of tisagenlecleucel therapy on Patient reported outcomes
Duration of Response (DOR) Per IRC 1 year 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).
Overall Survival (OS) 2 years Time from tisagenlecleucel infusion to death due to any cause
Cmax; Cellular Kinetic Parameter of Tisagenlecleucel 2 years The maximum (peak) observed in peripheral blood or other body fluid drug concentration after single dose administration (% or copies/ µg)
AUC0-28; Cellular Kinetic Parameter of Tisagenlecleucel 2 years The AUC from time zero to day 28, in peripheral blood (%\*days or days\*copies/ µg)
Summary of Exposure of CD3+ Tisagenlecleucel Cells in Peripheral Blood 2 years In vivo cellular kinetics of CD3+ tisagenlecleucel cells detected by flow cytometry
Summary Scores of PRO Measured by SF-36v2 Quality of Life Questionnaire 2 years Effect of tisagenlecleucel therapy on Patient reported outcomes
Cellular Immunogenicity 2 years Presence of T lymphocytes activated by the tisagenlecleucel protein
Trial Locations
- Locations (11)
City of Hope National Medical Center
🇺🇸Duarte, California, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
H Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Uni of Chi Medi Ctr Hema and Onco
🇺🇸Chicago, Illinois, United States
Univ of Kansas Hosp and Med Ctr
🇺🇸Kansas City, Kansas, United States
Michigan Med University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Oregon Health Sciences University
🇺🇸Portland, Oregon, United States
University of Pennsylvania Clinical
🇺🇸Philadelphia, Pennsylvania, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Novartis Investigative Site
🇬🇧London, United Kingdom
Amsterdam UMC, locatie AMC
🇳🇱Amsterdam, Netherlands