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

August 11, 2022 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Wien, Austria, 1090
        • Novartis Investigative Site
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Novartis Investigative Site
  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University School of Medicine SC CTL019
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center Hematology and Oncology
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Hospital and Medical Center U of Kansas Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Tisagenlecleucel+Pembrolizumab
Biological: Tisagenlecleucel
Gene modified autologous T cells
Other Names:
  • CTL019
Drug: Pembrolizumab
anti PD-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percent of participants recieving pembrolizumab per protocol schedule
Time Frame: 21 days after first pembrolizumab infusion
21 days after first pembrolizumab infusion
Dose Timing part: Incidence of dose limiting toxicities (DLTs)
Time Frame: 21 days after first pembrolizumab infusion
21 days after first pembrolizumab infusion
Expansion part: Overall response rate (ORR)
Time Frame: 3 month post tisagenlecleucel infusion
3 month post tisagenlecleucel infusion

Secondary Outcome Measures

Outcome Measure
Time Frame
Progression Free Survival (PFS)
Time Frame: 24 months
24 months
Overall Survival (OS)
Time Frame: 24 months
24 months
Duration of Response (DOR)
Time Frame: 24 months
24 months
In vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues by qPCR and flow cytometry
Time Frame: 24 months
24 months
Impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel by qPCR and flow cytometry
Time Frame: 24 months
24 months
Immunogenicity measured by antibody titres specific to tisagenlecleucel molecule and by the presence of T lymphocytes activated by the tisagenlecleucel protein
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 9, 2018

Primary Completion (Actual)

July 20, 2021

Study Completion (Actual)

July 20, 2021

Study Registration Dates

First Submitted

August 1, 2018

First Submitted That Met QC Criteria

August 9, 2018

First Posted (Actual)

August 14, 2018

Study Record Updates

Last Update Posted (Actual)

August 15, 2022

Last Update Submitted That Met QC Criteria

August 11, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CCTL019J2101
  • 2018-000973-57 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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