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

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ClinicalTrials.gov Identifier: NCT03876028
Recruitment Status : Not yet recruiting
First Posted : March 15, 2019
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE March 13, 2019
First Posted Date  ICMJE March 15, 2019
Last Update Posted Date March 15, 2019
Estimated Study Start Date  ICMJE March 27, 2019
Estimated Primary Completion Date May 25, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 13, 2019)
  • Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 24 months ]
    Month 24 is planned study end
  • Severity of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 24 months ]
    Month 24 is planned study end
  • Ibrutinib dose modification following tisagenlecleucel infusion [ Time Frame: 24 months ]
    Month 24 is planned study end
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2019)
  • Response Rate [ Time Frame: Month 3 ]
    3-months post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria
  • Response Rate [ Time Frame: Month 6 ]
    6-month post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria
  • Overall Response Rate [ Time Frame: 24 months ]
  • Duration of Response [ Time Frame: 24 months ]
  • Progression Free Survival (PFS) [ Time Frame: 24 months ]
  • Overall Survival (OS) [ Time Frame: 24 months ]
  • Tisagenlecleucel transgene concentrations [ Time Frame: 24 months ]
    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.
  • Cellular kinetics of Tisagenlecleucel (Cmax) [ Time Frame: 24 months ]
    Cmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
  • Cellular kinetics of Tisagenlecleucel (Tmax) [ Time Frame: 24 months ]
    Tmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
  • Cellular kinetics of Tisagenlecleucel (AUC) [ Time Frame: 24 months ]
    AUC cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
  • Cellular kinetics of Tisagenlecleucel (Clast) [ Time Frame: 24 month ]
    Clast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
  • Cellular kinetics of Tisagenlecleucel (Tlast) [ Time Frame: 24 month ]
    Tlast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
  • Anti-drug antibody (ADA) response to Tisagenlecleucel (humoral immunogenicity) [ Time Frame: 24 months ]
    Pre-existing and treatment related immunogenicity (humoral) of tisagenlecleucel will be characterized by flow cytometry
  • Anti- tisagenlecleucel t-cell response (cellular immunogenicity) [ Time Frame: 24 months ]
    Pre-existing and treatment related immunogenicity (cellular) of tisagenlecleucel will be characterized IFN-g staining and flow cytometry
  • Characterize cellular kinetic parameters in the presence of ADA and/or anti-tisagenlecleucel t-cell response [ Time Frame: 24 months ]
  • Characterize efficacy of tisagenlecleucel in the presence of ADA and/or anti-tisagenlecleucel t-cell response [ Time Frame: 24 month ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Tisagenlecleucel in Combination With Ibrutinib in r/r Diffuse Large B-cell Lymphoma Patients
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Parallel Assignment
Intervention Model Description:
"The study will enroll patients into two arms in parallel: Arm 1: Patients will start ibrutinib treatment before leukapheresis. Arm 2: Patients will start ibrutinib treatment after leukapheresis. Approximately 3-6 patients will be enrolled into each of the two arms in parallel. An early safety review will be performed after these patients have received sufficient ibrutinib treatment and tisagenlecleucel infusion, and have completed at least 21 days of follow up. Additional patients (up to 20 total) will be enrolled into both arms to further characterize the safety, tolerability and preliminary efficacy of ibrutinib in combination with tisagenlecleucel."
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diffuse Large B-cell Lymphoma
Intervention  ICMJE
  • Biological: Tisagenlecleucel
    Infusion
  • Drug: Ibrutinib
    Oral (tablets or capsules)
Study Arms  ICMJE
  • Experimental: Ibrutinib (before leukapheresis) + Tisagenlecleucel
    Patients will start ibrutinib treatment before leukapheresis
    Interventions:
    • Biological: Tisagenlecleucel
    • Drug: Ibrutinib
  • Experimental: Ibrutinib (after leukapheresis) + Tisagenlecleucel
    Patients will start ibrutinib treatment after leukapheresis.
    Interventions:
    • Biological: Tisagenlecleucel
    • Drug: Ibrutinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: March 13, 2019)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 25, 2022
Estimated Primary Completion Date May 25, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03876028
Other Study ID Numbers  ICMJE CCTL019L12101C
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Novartis
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP