Clinical Trials /

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

NCT03630159

Description:

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.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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.

Clinical Trial IDs

  • ORG STUDY ID: CCTL019J2101
  • NCT ID: NCT03630159

Conditions

  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
TisagenlecleucelCTL019Tisagenlecleucel+Pembrolizumab
PembrolizumabTisagenlecleucel+Pembrolizumab

Purpose

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 Arms

NameTypeDescriptionInterventions
Tisagenlecleucel+PembrolizumabExperimental
  • Tisagenlecleucel
  • Pembrolizumab

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percent of participants recieving pembrolizumab per protocol schedule
Time Frame:21 days after first pembrolizumab infusion
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of Response (DOR)
Time Frame:24 months
Safety Issue:
Description:
Measure:Progression Free Survival (PFS)
Time Frame:24 months
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:24 months
Safety Issue:
Description:
Measure:In vivo cellular kinetics of tisagenlecleucel in blood, bone marrow, lymph nodes and other tissues by qPCR and flow cytometry
Time Frame:24 months
Safety Issue:
Description:
Measure:Impact of pembrolizumab dosing strategy on the cellular kinetics of tisagenlecleucel by qPCR and flow cytometry
Time Frame:24 months
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial 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

Last Updated

February 6, 2020