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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Terminated

CT.gov ID

NCT03876028

Collaborator

(none)

Enrollment

Locations

Arms

28.7

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-cell Lymphoma	Biological: Tisagenlecleucel Drug: Ibrutinib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Parallel Assignment

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.""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."

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 11, 2019

Actual Primary Completion Date :

Nov 1, 2021

Actual Study Completion Date :

Nov 1, 2021

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Confirmed DLBCL as per the local histopathological assessment.
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.
Measurable disease at time of enrollment.
Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening.
Adequate renal, liver, and bone marrow, organ function, and minimum level of pulmonary reserve.

Exclusion Criteria:

Patients with Richter's transformation, Burkitt's lymphoma, and primary DLBCL of the CNS.
Prior anti-CD19 directed therapy.
Prior gene therapy.
Prior adoptive T cell therapy.
Prior ibrutinib therapy within the 30 days prior to screening.
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.
Prior allogeneic HSCT
. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	H Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
2	University of Pennsylvania, Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104