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

Primary Purpose

Diffuse Large B-cell Lymphoma

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Tisagenlecleucel

Ibrutinib

About this trial

This is an interventional treatment trial for Diffuse Large B-cell Lymphoma focused on measuring Lymphoma, Diffuse Large B-cell lymphoma, DLBCL, r/r Diffuse Large B-cell Lymphoma, relapsed/refractory DLBCL, CTL019, Tisagenlecleucel, Ibrutinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

H Lee Moffitt Cancer Center and Research Institute
University of Pennsylvania, Abramson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Ibrutinib (before leukapheresis) + Tisagenlecleucel

Ibrutinib (after leukapheresis) + Tisagenlecleucel

Arm Description

Patients will start ibrutinib treatment before leukapheresis

Patients will start ibrutinib treatment after leukapheresis.

Outcomes

Primary Outcome Measures

Incidence of adverse events (AEs) and serious adverse events (SAEs)

Month 24 is planned study end

Severity of adverse events (AEs) and serious adverse events (SAEs)

Month 24 is planned study end

Ibrutinib dose modification following tisagenlecleucel infusion

Month 24 is planned study end

Secondary Outcome Measures

Response Rate

3-months post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria

Response Rate

6-month post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria

Overall Response Rate

Duration of Response

Progression Free Survival (PFS)

Overall Survival (OS)

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.

Cellular kinetics of Tisagenlecleucel (Cmax)

Cmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

Cellular kinetics of Tisagenlecleucel (Tmax)

Tmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

Cellular kinetics of Tisagenlecleucel (AUC)

AUC cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

Cellular kinetics of Tisagenlecleucel (Clast)

Clast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

Cellular kinetics of Tisagenlecleucel (Tlast)

Tlast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

Anti-drug antibody (ADA) response to Tisagenlecleucel (humoral immunogenicity)

Pre-existing and treatment related immunogenicity (humoral) of tisagenlecleucel will be characterized by flow cytometry

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

Characterize cellular kinetic parameters in the presence of ADA and/or anti-tisagenlecleucel t-cell response

Characterize efficacy of tisagenlecleucel in the presence of ADA and/or anti-tisagenlecleucel t-cell response

Full Information

NCT ID

NCT03876028

First Posted

March 13, 2019

Last Updated

January 27, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03876028

Brief Title

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

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Terminated

Why Stopped

Business reasons

Study Start Date

June 11, 2019 (Actual)

Primary Completion Date

November 1, 2021 (Actual)

Study Completion Date

November 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

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."

Masking

None (Open Label)

Allocation

N/A

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ibrutinib (before leukapheresis) + Tisagenlecleucel

Arm Type

Experimental

Arm Description

Patients will start ibrutinib treatment before leukapheresis

Arm Title

Ibrutinib (after leukapheresis) + Tisagenlecleucel

Arm Type

Experimental

Arm Description

Patients will start ibrutinib treatment after leukapheresis.

Intervention Type

Biological

Intervention Name(s)

Tisagenlecleucel

Intervention Description

Infusion

Intervention Type

Drug

Intervention Name(s)

Ibrutinib

Intervention Description

Oral (tablets or capsules)

Primary Outcome Measure Information:

Title

Incidence of adverse events (AEs) and serious adverse events (SAEs)

Description

Month 24 is planned study end

Time Frame

24 months

Title

Severity of adverse events (AEs) and serious adverse events (SAEs)

Description

Month 24 is planned study end

Time Frame

24 months

Title

Ibrutinib dose modification following tisagenlecleucel infusion

Description

Month 24 is planned study end

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Response Rate

Description

3-months post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria

Time Frame

Month 3

Title

Response Rate

Description

6-month post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria

Time Frame

Month 6

Title

Overall Response Rate

Time Frame

24 months

Title

Duration of Response

Time Frame

24 months

Title

Progression Free Survival (PFS)

Time Frame

24 months

Title

Overall Survival (OS)

Time Frame

24 months

Title

Tisagenlecleucel transgene concentrations

Description

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.

Time Frame

24 months

Title

Cellular kinetics of Tisagenlecleucel (Cmax)

Description

Cmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

Time Frame

24 months

Title

Cellular kinetics of Tisagenlecleucel (Tmax)

Description

Tmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

Time Frame

24 months

Title

Cellular kinetics of Tisagenlecleucel (AUC)

Description

AUC cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

Time Frame

24 months

Title

Cellular kinetics of Tisagenlecleucel (Clast)

Description

Clast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

Time Frame

24 month

Title

Cellular kinetics of Tisagenlecleucel (Tlast)

Description

Tlast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib

Time Frame

24 month

Title

Anti-drug antibody (ADA) response to Tisagenlecleucel (humoral immunogenicity)

Description

Pre-existing and treatment related immunogenicity (humoral) of tisagenlecleucel will be characterized by flow cytometry

Time Frame

24 months

Title

Anti- tisagenlecleucel t-cell response (cellular immunogenicity)

Description

Pre-existing and treatment related immunogenicity (cellular) of tisagenlecleucel will be characterized IFN-g staining and flow cytometry

Time Frame

24 months

Title

Characterize cellular kinetic parameters in the presence of ADA and/or anti-tisagenlecleucel t-cell response

Time Frame

24 months

Title

Characterize efficacy of tisagenlecleucel in the presence of ADA and/or anti-tisagenlecleucel t-cell response

Time Frame

24 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Facility Information:

Facility Name

H Lee Moffitt Cancer Center and Research Institute

City

Tampa

State/Province

Florida

ZIP/Postal Code

33612

Country

United States

Facility Name

University of Pennsylvania, Abramson Cancer Center

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19104

Country

United States

12. IPD Sharing Statement

Links:

URL

https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17966

Description

Study results

URL

https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=1223

Description

A Plain Language Trial Summary is available on novctrd.com

Learn more about this trial

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

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