Study of Tisagenlecleucel in Combination With Pembrolizumab in r/r Diffuse Large B-cell Lymphoma Patients
- Conditions
- Diffuse Large B-cell Lymphoma
- Interventions
- Biological: TisagenlecleucelDrug: Pembrolizumab
- Registration Number
- NCT03630159
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
A multi-center, open-label, phase Ib study to evaluate the safety and efficacy of the administration of tisagenlecleucel in combination with pembrolizumab in patients with r/r DLBCL who have received 2 or more lines of systemic therapy, including an anti-CD20 and anthracycline based chemotherapy and having failed to or are not candidates for ASCT. The study will consist of 2 parts: dose timing selection part and expansion part.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- Confirmed DLBCL per local histopathology assessment.
- Relapsed or refractory disease after having recieved 2 or more lines of systemic therapy, including anti-CD20 and anthracycline based chemotherapy, and either having progressed after (or relapsed after) ASCT, or being not candidates for or not consenting to ASCT.
- Measurable disease at time of enrollment
- ECOG performance status that is either 0 or 1 at screening.
- Patients with Richter's transformation, and Burkitt lymphoma, and primary DLBCL of CNS.
- Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy.
- Patients with active CNS involvement are excluded, except if the CNS involvement has been effectively treated and provided that local treatment was >4 weeks before enrollment.
- Prior allogeneic HSCT.
- Unstable angina and/or myocardial infarction and/or coronary artery bypass graft (CABG), or stroke within 6 months prior to screening, and/or impaired cardiac function or clinically significant cardiac disease
- Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibodies, other immune checkpoint inhibitors.
- History of interstitial lung disease or (non-infectious) pneumonitis that required oral or intravenous steroids (other than COPD exacerbation) or current pneumonitis.
Other protocol-defined inclusion/exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tisagenlecleucel+Pembrolizumab Tisagenlecleucel - Tisagenlecleucel+Pembrolizumab Pembrolizumab -
- Primary Outcome Measures
Name Time Method Percent of participants recieving pembrolizumab per protocol schedule 21 days after first pembrolizumab infusion Expansion part: Overall response rate (ORR) 3 month post tisagenlecleucel infusion Dose Timing part: Incidence of dose limiting toxicities (DLTs) 21 days after first pembrolizumab infusion
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) 24 months Impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel by qPCR and flow cytometry 24 months Duration of Response (DOR) 24 months Progression Free Survival (PFS) 24 months Immunogenicity measured by antibody titres specific to tisagenlecleucel molecule and by the presence of T lymphocytes activated by the tisagenlecleucel protein 24 months In vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues by qPCR and flow cytometry 24 months
Trial Locations
- Locations (4)
Emory University School of Medicine SC CTL019
🇺🇸Atlanta, Georgia, United States
University of Kansas Hospital and Medical Center U of Kansas Cancer Center
🇺🇸Kansas City, Kansas, United States
University of Chicago Medical Center Hematology and Oncology
🇺🇸Chicago, Illinois, United States
Novartis Investigative Site
🇨🇦Montreal, Quebec, Canada