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

Phase 1

Terminated

• Conditions: Diffuse Large B-cell Lymphoma
• Interventions: Biological: Tisagenlecleucel; Drug: Ibrutinib

• Registration Number: NCT03876028
• Lead Sponsor: 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-03-13
• Study First Submitted QC: 2019-03-13
• Study First Posted: 2019-03-15
• Study Start: 2019-06-11
• Primary Completion: 2021-11-01
• Study Completion: 2021-11-01
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-27
• Last Update Posted: 2023-01-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ibrutinib (after leukapheresis) + Tisagenlecleucel	Tisagenlecleucel	Patients will start ibrutinib treatment after leukapheresis.
Ibrutinib (before leukapheresis) + Tisagenlecleucel	Tisagenlecleucel	Patients will start ibrutinib treatment before leukapheresis
Ibrutinib (before leukapheresis) + Tisagenlecleucel	Ibrutinib	Patients will start ibrutinib treatment before leukapheresis
Ibrutinib (after leukapheresis) + Tisagenlecleucel	Ibrutinib	Patients will start ibrutinib treatment after leukapheresis.

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events (AEs) and serious adverse events (SAEs)	24 months	Month 24 is planned study end
Severity of adverse events (AEs) and serious adverse events (SAEs)	24 months	Month 24 is planned study end
Ibrutinib dose modification following tisagenlecleucel infusion	24 months	Month 24 is planned study end

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	24 months
Cellular kinetics of Tisagenlecleucel (Tmax)	24 months	Tmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
Cellular kinetics of Tisagenlecleucel (AUC)	24 months	AUC cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
Response Rate	Month 6	6-month post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria
Duration of Response	24 months
Cellular kinetics of Tisagenlecleucel (Clast)	24 month	Clast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
Tisagenlecleucel transgene concentrations	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.
Characterize efficacy of tisagenlecleucel in the presence of ADA and/or anti-tisagenlecleucel t-cell response	24 month
Overall Survival (OS)	24 months
Cellular kinetics of Tisagenlecleucel (Cmax)	24 months	Cmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
Anti-drug antibody (ADA) response to Tisagenlecleucel (humoral immunogenicity)	24 months	Pre-existing and treatment related immunogenicity (humoral) of tisagenlecleucel will be characterized by flow cytometry
Anti- tisagenlecleucel t-cell response (cellular immunogenicity)	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	24 months
Cellular kinetics of Tisagenlecleucel (Tlast)	24 month	Tlast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
Overall Response Rate	24 months

Trial Locations

Locations (2)

H Lee Moffitt Cancer Center and Research Institute; 🇺🇸 Tampa, Florida, United States

University of Pennsylvania, Abramson Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States