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

Diffuse Large B-cell Lymphoma Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03876028
• Other study ID #: CCTL019L12101C
• Status: Terminated
• Phase: Phase 1
• Start date: June 11, 2019
• Est. completion date: November 1, 2021

Study information

• Verified date: January 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 10
• Est. completion date: November 1, 2021
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Biological:
• Tisagenlecleucel
Infusion

Drug:
• Ibrutinib
Oral (tablets or capsules)

Locations

Country	Name	City	State
United States	University of Pennsylvania, Abramson Cancer Center	Philadelphia	Pennsylvania
United States	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events (AEs) and serious adverse events (SAEs)	Month 24 is planned study end	24 months
Primary	Severity of adverse events (AEs) and serious adverse events (SAEs)	Month 24 is planned study end	24 months
Primary	Ibrutinib dose modification following tisagenlecleucel infusion	Month 24 is planned study end	24 months
Secondary	Response Rate	3-months post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria	Month 3
Secondary	Response Rate	6-month post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria	Month 6
Secondary	Overall Response Rate		24 months
Secondary	Duration of Response		24 months
Secondary	Progression Free Survival (PFS)		24 months
Secondary	Overall Survival (OS)		24 months
Secondary	Tisagenlecleucel transgene concentrations	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.	24 months
Secondary	Cellular kinetics of Tisagenlecleucel (Cmax)	Cmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib	24 months
Secondary	Cellular kinetics of Tisagenlecleucel (Tmax)	Tmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib	24 months
Secondary	Cellular kinetics of Tisagenlecleucel (AUC)	AUC cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib	24 months
Secondary	Cellular kinetics of Tisagenlecleucel (Clast)	Clast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib	24 month
Secondary	Cellular kinetics of Tisagenlecleucel (Tlast)	Tlast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib	24 month
Secondary	Anti-drug antibody (ADA) response to Tisagenlecleucel (humoral immunogenicity)	Pre-existing and treatment related immunogenicity (humoral) of tisagenlecleucel will be characterized by flow cytometry	24 months
Secondary	Anti- tisagenlecleucel t-cell response (cellular immunogenicity)	Pre-existing and treatment related immunogenicity (cellular) of tisagenlecleucel will be characterized IFN-g staining and flow cytometry	24 months
Secondary	Characterize cellular kinetic parameters in the presence of ADA and/or anti-tisagenlecleucel t-cell response		24 months
Secondary	Characterize efficacy of tisagenlecleucel in the presence of ADA and/or anti-tisagenlecleucel t-cell response		24 month

External Links

•   A Plain Language Trial Summary is available on novctrd.com
•   Study results