Clinical trial NCT03876028: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Diffuse Large B-cell Lymphoma
Keywords: Lymphoma
Diffuse Large B-cell lymphoma
DLBCL
r/r Diffuse Large B-cell Lymphoma
relapsed/refractory DLBCL
CTL019
Tisagenlecleucel
Ibrutinib
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2019-03-15
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: PARALLEL
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."
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Incidence of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 24 months
measure: Severity of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 24 months
measure: Ibrutinib dose modification following tisagenlecleucel infusion
timeFrame: 24 months
Secondary outcomes:
measure: Response Rate
timeFrame: Month 3
measure: Response Rate
timeFrame: Month 6
measure: Overall Response Rate
timeFrame: 24 months
measure: Duration of Response
timeFrame: 24 months
measure: Progression Free Survival (PFS)
timeFrame: 24 months
measure: Overall Survival (OS)
timeFrame: 24 months
measure: Tisagenlecleucel transgene concentrations
timeFrame: 24 months
measure: Cellular kinetics of Tisagenlecleucel (Cmax)
timeFrame: 24 months
measure: Cellular kinetics of Tisagenlecleucel (Tmax)
timeFrame: 24 months
measure: Cellular kinetics of Tisagenlecleucel (AUC)
timeFrame: 24 months
measure: Cellular kinetics of Tisagenlecleucel (Clast)
timeFrame: 24 month
measure: Cellular kinetics of Tisagenlecleucel (Tlast)
timeFrame: 24 month
measure: Anti-drug antibody (ADA) response to Tisagenlecleucel (humoral immunogenicity)
timeFrame: 24 months
measure: Anti- tisagenlecleucel t-cell response (cellular immunogenicity)
timeFrame: 24 months
measure: Characterize cellular kinetic parameters in the presence of ADA and/or anti-tisagenlecleucel t-cell response
timeFrame: 24 months
measure: Characterize efficacy of tisagenlecleucel in the presence of ADA and/or anti-tisagenlecleucel t-cell response
timeFrame: 24 month
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Philadelphia
country: United States
facility: University of Pennsylvania, Abramson Cancer Center
state: Pennsylvania
Study officials:
References: