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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 : Recruiting
First Posted : March 15, 2019
Last Update Posted : October 16, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Diffuse Large B-cell Lymphoma Biological: Tisagenlecleucel Drug: Ibrutinib Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
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
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
Actual Study Start Date : June 11, 2019
Estimated Primary Completion Date : July 13, 2022
Estimated Study Completion Date : July 13, 2022


Arm Intervention/treatment
Experimental: Ibrutinib (before leukapheresis) + Tisagenlecleucel
Patients will start ibrutinib treatment before leukapheresis
Biological: Tisagenlecleucel
Infusion

Drug: Ibrutinib
Oral (tablets or capsules)

Experimental: Ibrutinib (after leukapheresis) + Tisagenlecleucel
Patients will start ibrutinib treatment after leukapheresis.
Biological: Tisagenlecleucel
Infusion

Drug: Ibrutinib
Oral (tablets or capsules)




Primary Outcome Measures :
  1. Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 24 months ]
    Month 24 is planned study end

  2. Severity of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 24 months ]
    Month 24 is planned study end

  3. Ibrutinib dose modification following tisagenlecleucel infusion [ Time Frame: 24 months ]
    Month 24 is planned study end


Secondary Outcome Measures :
  1. Response Rate [ Time Frame: Month 3 ]
    3-months post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria

  2. Response Rate [ Time Frame: Month 6 ]
    6-month post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria

  3. Overall Response Rate [ Time Frame: 24 months ]
  4. Duration of Response [ Time Frame: 24 months ]
  5. Progression Free Survival (PFS) [ Time Frame: 24 months ]
  6. Overall Survival (OS) [ Time Frame: 24 months ]
  7. 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.

  8. Cellular kinetics of Tisagenlecleucel (Cmax) [ Time Frame: 24 months ]
    Cmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

  9. Cellular kinetics of Tisagenlecleucel (Tmax) [ Time Frame: 24 months ]
    Tmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

  10. Cellular kinetics of Tisagenlecleucel (AUC) [ Time Frame: 24 months ]
    AUC cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

  11. Cellular kinetics of Tisagenlecleucel (Clast) [ Time Frame: 24 month ]
    Clast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

  12. Cellular kinetics of Tisagenlecleucel (Tlast) [ Time Frame: 24 month ]
    Tlast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

  13. 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

  14. 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

  15. Characterize cellular kinetic parameters in the presence of ADA and/or anti-tisagenlecleucel t-cell response [ Time Frame: 24 months ]
  16. Characterize efficacy of tisagenlecleucel in the presence of ADA and/or anti-tisagenlecleucel t-cell response [ Time Frame: 24 month ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03876028


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Florida
H Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Brooke Olmo    813-745-5221    Brook.Olmo@moffitt.org   
Principal Investigator: Julio Chavez         
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact    215-662-6394      
Principal Investigator: Stephen Schuster         
Sponsors and Collaborators
Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03876028     History of Changes
Other Study ID Numbers: CCTL019L12101C
First Posted: March 15, 2019    Key Record Dates
Last Update Posted: October 16, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Lymphoma
Diffuse Large B-cell lymphoma
DLBCL
r/r Diffuse Large B-cell Lymphoma
relapsed/refractory DLBCL
CTL019
Tisagenlecleucel
Ibrutinib
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin