NCT03630159

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Oct 2018

Typical duration for phase_1

Geographic Reach
3 countries

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 1, 2018

Completed
13 days until next milestone

First Posted

Study publicly available on registry

August 14, 2018

Completed
2 months until next milestone

Study Start

First participant enrolled

October 9, 2018

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 20, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 20, 2021

Completed
Last Updated

August 15, 2022

Status Verified

August 1, 2022

Enrollment Period

2.8 years

First QC Date

August 1, 2018

Last Update Submit

August 11, 2022

Conditions

Keywords

Lymphoma tisagenlecleucelDiffuse Large B-cell LymphomaCTL019PORTIADLBCLtisagenlecleucelpembrolizumabr/r Diffuse large B-cell Lymphomarelapsed/refractory Diffuse large B-cell Lymphoma

Outcome Measures

Primary Outcomes (3)

  • Percent of participants recieving pembrolizumab per protocol schedule

    21 days after first pembrolizumab infusion

  • Dose Timing part: Incidence of dose limiting toxicities (DLTs)

    21 days after first pembrolizumab infusion

  • Expansion part: Overall response rate (ORR)

    3 month post tisagenlecleucel infusion

Secondary Outcomes (6)

  • Duration of Response (DOR)

    24 months

  • Progression Free Survival (PFS)

    24 months

  • Overall Survival (OS)

    24 months

  • In vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues by qPCR and flow cytometry

    24 months

  • Impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel by qPCR and flow cytometry

    24 months

  • +1 more secondary outcomes

Study Arms (1)

Tisagenlecleucel+Pembrolizumab

EXPERIMENTAL
Biological: TisagenlecleucelDrug: Pembrolizumab

Interventions

Gene modified autologous T cells

Also known as: CTL019
Tisagenlecleucel+Pembrolizumab

anti PD-1

Tisagenlecleucel+Pembrolizumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Emory University School of Medicine SC CTL019

Atlanta, Georgia, 30322, United States

Location

University of Chicago Medical Center Hematology and Oncology

Chicago, Illinois, 60637, United States

Location

University of Kansas Hospital and Medical Center U of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

Novartis Investigative Site

Vienna, 1090, Austria

Location

Novartis Investigative Site

Montreal, Quebec, H1T 2M4, Canada

Location

Related Publications (2)

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

tisagenlecleucelpembrolizumab

Condition Hierarchy (Ancestors)

Lymphoma, B-CellLymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Masking Details
None (Open label)
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 1, 2018

First Posted

August 14, 2018

Study Start

October 9, 2018

Primary Completion

July 20, 2021

Study Completion

July 20, 2021

Last Updated

August 15, 2022

Record last verified: 2022-08

Data Sharing

IPD Sharing
Will not share

Locations