Clinical Trials /

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

NCT03876028

Description:

A multi-center, open-label, phase Ib study to evaluate the safety and tolerability of the administration of tisagenlecleucel in combination with ibrutinib in patients with r/r DLBCL who have received two or more lines of systemic therapy, including an anti-CD20 and anthracycline based chemotherapy, and who have progressed after or are not candidates for ASCT.

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 Ibrutinib in r/r Diffuse Large B-cell Lymphoma Patients
  • Official Title: A Phase Ib, Multicenter Study to Determine the Safety and Tolerability of Tisagenlecleucel in Combination With Ibrutinib in Adult Patients With Relapsed and/or Refractory Diffuse Large B-cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: CCTL019L12101C
  • NCT ID: NCT03876028

Conditions

  • Diffuse Large B-cell Lymphoma

Interventions

DrugSynonymsArms
TisagenlecleucelIbrutinib (after leukapheresis) + Tisagenlecleucel
IbrutinibIbrutinib (after leukapheresis) + Tisagenlecleucel

Purpose

A multi-center, open-label, phase Ib study to evaluate the safety and tolerability of the administration of tisagenlecleucel in combination with ibrutinib in patients with r/r DLBCL who have received two or more lines of systemic therapy, including an anti-CD20 and anthracycline based chemotherapy, and who have progressed after or are not candidates for ASCT.

Trial Arms

NameTypeDescriptionInterventions
Ibrutinib (before leukapheresis) + TisagenlecleucelExperimentalPatients will start ibrutinib treatment before leukapheresis
  • Tisagenlecleucel
  • Ibrutinib
Ibrutinib (after leukapheresis) + TisagenlecleucelExperimentalPatients will start ibrutinib treatment after leukapheresis.
  • Tisagenlecleucel
  • Ibrutinib

Eligibility Criteria

        Inclusion Criteria:

          1. Confirmed DLBCL as per the local histopathological assessment.

          2. Relapsed or refractory disease having received 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 ineligible for or not consenting to ASCT.

          3. Measurable disease at time of enrollment.

          4. Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at
             screening.

          5. Adequate renal, liver, and bone marrow, organ function, and minimum level of pulmonary
             reserve.

        Exclusion Criteria:

          1. Patients with Richter's transformation, Burkitt's lymphoma, and primary DLBCL of the
             CNS.

          2. Prior anti-CD19 directed therapy.

          3. Prior gene therapy.

          4. Prior adoptive T cell therapy.

          5. Prior ibrutinib therapy within the 30 days prior to screening.

          6. 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.

          7. Prior allogeneic HSCT

          8. . Significant cardiac abnormality including history of myocardial infarction within 6
             months prior to screening as detailed in the study protocol.

        Other eligibility criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame:24 months
Safety Issue:
Description:Month 24 is planned study end

Secondary Outcome Measures

Measure:Response Rate
Time Frame:Month 3
Safety Issue:
Description:3-months post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria
Measure:Response Rate
Time Frame:Month 6
Safety Issue:
Description:6-month post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria
Measure:Overall Response Rate
Time Frame:24 months
Safety Issue:
Description:
Measure:Duration of Response
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:Tisagenlecleucel transgene concentrations
Time Frame:24 months
Safety Issue:
Description:qPCR will be used to measure tisagenlecleucel transgene concentrations in available tissue, such as peripheral blood, bone marrow, tumor/lymph node tissue, and/or CSF.
Measure:Cellular kinetics of Tisagenlecleucel (Cmax)
Time Frame:24 months
Safety Issue:
Description:Cmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
Measure:Cellular kinetics of Tisagenlecleucel (Tmax)
Time Frame:24 months
Safety Issue:
Description:Tmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
Measure:Cellular kinetics of Tisagenlecleucel (AUC)
Time Frame:24 months
Safety Issue:
Description:AUC cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
Measure:Cellular kinetics of Tisagenlecleucel (Clast)
Time Frame:24 month
Safety Issue:
Description:Clast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
Measure:Cellular kinetics of Tisagenlecleucel (Tlast)
Time Frame:24 month
Safety Issue:
Description:Tlast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
Measure:Anti-drug antibody (ADA) response to Tisagenlecleucel (humoral immunogenicity)
Time Frame:24 months
Safety Issue:
Description:Pre-existing and treatment related immunogenicity (humoral) of tisagenlecleucel will be characterized by flow cytometry
Measure:Anti- tisagenlecleucel t-cell response (cellular immunogenicity)
Time Frame:24 months
Safety Issue:
Description:Pre-existing and treatment related immunogenicity (cellular) of tisagenlecleucel will be characterized IFN-g staining and flow cytometry
Measure:Characterize cellular kinetic parameters in the presence of ADA and/or anti-tisagenlecleucel t-cell response
Time Frame:24 months
Safety Issue:
Description:
Measure:Characterize efficacy of tisagenlecleucel in the presence of ADA and/or anti-tisagenlecleucel t-cell response
Time Frame:24 month
Safety Issue:
Description:

Details

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

Trial Keywords

  • Lymphoma
  • Diffuse Large B-cell lymphoma
  • DLBCL
  • r/r Diffuse Large B-cell Lymphoma
  • relapsed/refractory DLBCL
  • CTL019
  • Tisagenlecleucel
  • Ibrutinib

Last Updated

January 17, 2020