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.
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
Drug | Synonyms | Arms |
---|
Tisagenlecleucel | | Ibrutinib (after leukapheresis) + Tisagenlecleucel |
Ibrutinib | | Ibrutinib (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
Name | Type | Description | Interventions |
---|
Ibrutinib (before leukapheresis) + Tisagenlecleucel | Experimental | Patients will start ibrutinib treatment before leukapheresis | - Tisagenlecleucel
- Ibrutinib
|
Ibrutinib (after leukapheresis) + Tisagenlecleucel | Experimental | Patients 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: | Active, not 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
July 27, 2021