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

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

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.

Study Overview

• Status: Terminated
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Biological: Tisagenlecleucel; Drug: Ibrutinib

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H Lee Moffitt Cancer Center and Research Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, Abramson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)		24 months
Overall Survival (OS)		24 months
Overall Response Rate		24 months
Response Rate	3-months post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria	Month 3
Response Rate	6-month post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria	Month 6
Duration of Response		24 months
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
Cellular kinetics of Tisagenlecleucel (Cmax)	Cmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib	24 months
Cellular kinetics of Tisagenlecleucel (Tmax)	Tmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib	24 months
Cellular kinetics of Tisagenlecleucel (AUC)	AUC cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib	24 months
Cellular kinetics of Tisagenlecleucel (Clast)	Clast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib	24 month
Cellular kinetics of Tisagenlecleucel (Tlast)	Tlast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib	24 month
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
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
Characterize cellular kinetic parameters in the presence of ADA and/or anti-tisagenlecleucel t-cell response		24 months
Characterize efficacy of tisagenlecleucel in the presence of ADA and/or anti-tisagenlecleucel t-cell response		24 month

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2019
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 1, 2021

Study Registration Dates

• First Submitted: March 13, 2019
• First Submitted That Met QC Criteria: March 13, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): January 31, 2023
• Last Update Submitted That Met QC Criteria: January 27, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: DLBCL; Lymphoma; Ibrutinib; CTL019; Tisagenlecleucel; Diffuse Large B-cell lymphoma; r/r Diffuse Large B-cell Lymphoma; relapsed/refractory DLBCL
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: CCTL019L12101C

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No