Clinical trial NCT03630159: Study of Tisagenlecleucel in Combination With Pembrolizumab in r/r Diffuse Large B-cell Lymphoma Patients
Official title: Phase Ib Study of Tisagenlecleucel in Combination With Pembrolizumab in Relapsed/Refractory (r/r) Diffuse Large B-cell Lymphoma (DLBCL) Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diffuse Large B-cell Lymphoma
Keywords: Lymphoma tisagenlecleucel
Diffuse Large B-cell Lymphoma
CTL019
PORTIA
DLBCL
tisagenlecleucel
pembrolizumab
r/r Diffuse large B-cell Lymphoma
relapsed/refractory Diffuse large B-cell Lymphoma
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-08-14
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percent of participants recieving pembrolizumab per protocol schedule
timeFrame: 21 days after first pembrolizumab infusion
measure: Dose Timing part: Incidence of dose limiting toxicities (DLTs)
timeFrame: 21 days after first pembrolizumab infusion
measure: Expansion part: Overall response rate (ORR)
timeFrame: 3 month post tisagenlecleucel infusion
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: 24 months
measure: Progression Free Survival (PFS)
timeFrame: 24 months
measure: Overall Survival (OS)
timeFrame: 24 months
measure: In vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues by qPCR and flow cytometry
timeFrame: 24 months
measure: Impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel by qPCR and flow cytometry
timeFrame: 24 months
measure: Immunogenicity measured by antibody titres specific to tisagenlecleucel molecule and by the presence of T lymphocytes activated by the tisagenlecleucel protein
timeFrame: 24 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University School of Medicine SC CTL019
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center Hematology and Oncology
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Hospital and Medical Center U of Kansas Cancer Center
state: Kansas
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Jaeger U, Worel N, McGuirk JP, Riedell PA, Fleury I, Du Y, Han X, Pearson D, Redondo S, Waller EK. Safety and efficacy of tisagenlecleucel plus pembrolizumab in patients with r/r DLBCL: phase 1b PORTIA study results. Blood Adv. 2023 Jun 13;7(11):2283-2286. doi: 10.1182/bloodadvances.2022007779.
citation: Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.