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

Primary Purpose

Diffuse Large B-cell Lymphoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Tisagenlecleucel
Pembrolizumab
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Emory University School of Medicine SC CTL019
  • University of Chicago Medical Center Hematology and Oncology
  • University of Kansas Hospital and Medical Center U of Kansas Cancer Center
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tisagenlecleucel+Pembrolizumab

Arm Description

Outcomes

Primary Outcome Measures

Percent of participants recieving pembrolizumab per protocol schedule
Dose Timing part: Incidence of dose limiting toxicities (DLTs)
Expansion part: Overall response rate (ORR)

Secondary Outcome Measures

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

Full Information

First Posted
August 1, 2018
Last Updated
August 11, 2022
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03630159
Brief Title
Study of Tisagenlecleucel in Combination With Pembrolizumab in r/r Diffuse Large B-cell Lymphoma Patients
Acronym
PORTIA
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

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
October 9, 2018 (Actual)
Primary Completion Date
July 20, 2021 (Actual)
Study Completion Date
July 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Masking Description
None (Open label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tisagenlecleucel+Pembrolizumab
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Tisagenlecleucel
Other Intervention Name(s)
CTL019
Intervention Description
Gene modified autologous T cells
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
anti PD-1
Primary Outcome Measure Information:
Title
Percent of participants recieving pembrolizumab per protocol schedule
Time Frame
21 days after first pembrolizumab infusion
Title
Dose Timing part: Incidence of dose limiting toxicities (DLTs)
Time Frame
21 days after first pembrolizumab infusion
Title
Expansion part: Overall response rate (ORR)
Time Frame
3 month post tisagenlecleucel infusion
Secondary Outcome Measure Information:
Title
Duration of Response (DOR)
Time Frame
24 months
Title
Progression Free Survival (PFS)
Time Frame
24 months
Title
Overall Survival (OS)
Time Frame
24 months
Title
In vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues by qPCR and flow cytometry
Time Frame
24 months
Title
Impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel by qPCR and flow cytometry
Time Frame
24 months
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Emory University School of Medicine SC CTL019
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Chicago Medical Center Hematology and Oncology
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Kansas Hospital and Medical Center U of Kansas Cancer Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Novartis Investigative Site
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
36044388
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.
Results Reference
derived
PubMed Identifier
34515338
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.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17956
Description
Novartis results database
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1106
Description
A Plain Language Trial Summary is available on novctrd.com

Learn more about this trial

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

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