Study of Tisagenlecleucel in Combination With Pembrolizumab in r/r Diffuse Large B-cell Lymphoma Patients

Diffuse Large B-cell Lymphoma Clinical Trial

— PORTIA  

Official title:

Phase Ib Study of Tisagenlecleucel in Combination With Pembrolizumab in Relapsed/Refractory (r/r) Diffuse Large B-cell Lymphoma (DLBCL) Patients.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03630159
• Other study ID #: CCTL019J2101
• Secondary ID: 2018-000973-57
• Status: Completed
• Phase: Phase 1
• Start date: October 9, 2018
• Est. completion date: July 20, 2021

Study information

• Verified date: August 2022
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 20, 2021
• Est. primary completion date: July 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Biological:
• Tisagenlecleucel
Gene modified autologous T cells

Drug:
• Pembrolizumab
anti PD-1

Locations

Country	Name	City	State
Austria	Novartis Investigative Site	Wien
Canada	Novartis Investigative Site	Montreal	Quebec
United States	Emory University School of Medicine SC CTL019	Atlanta	Georgia
United States	University of Chicago Medical Center Hematology and Oncology	Chicago	Illinois
United States	University of Kansas Hospital and Medical Center U of Kansas Cancer Center	Kansas City	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of participants recieving pembrolizumab per protocol schedule		21 days after first pembrolizumab infusion
Primary	Dose Timing part: Incidence of dose limiting toxicities (DLTs)		21 days after first pembrolizumab infusion
Primary	Expansion part: Overall response rate (ORR)		3 month post tisagenlecleucel infusion
Secondary	Duration of Response (DOR)		24 months
Secondary	Progression Free Survival (PFS)		24 months
Secondary	Overall Survival (OS)		24 months
Secondary	In vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues by qPCR and flow cytometry		24 months
Secondary	Impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel by qPCR and flow cytometry		24 months
Secondary	Immunogenicity measured by antibody titres specific to tisagenlecleucel molecule and by the presence of T lymphocytes activated by the tisagenlecleucel protein		24 months

External Links

•   A Plain Language Trial Summary is available on novctrd.com
•   Novartis results database