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

January 27, 2023 updated by: Novartis Pharmaceuticals

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
10

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: 24 months
Month 24 is planned study end
24 months
Severity of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: 24 months
Month 24 is planned study end
24 months
Ibrutinib dose modification following tisagenlecleucel infusion
Time Frame: 24 months
Month 24 is planned study end
24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: 24 months
24 months
Overall Survival (OS)
Time Frame: 24 months
24 months
Overall Response Rate
Time Frame: 24 months
24 months
Response Rate
Time Frame: Month 3
3-months post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria
Month 3
Response Rate
Time Frame: Month 6
6-month post tisagenlecleucel infusion, assessed by local investigator according to Lugano criteria
Month 6
Duration of Response
Time Frame: 24 months
24 months
Tisagenlecleucel transgene concentrations
Time Frame: 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.
24 months
Cellular kinetics of Tisagenlecleucel (Cmax)
Time Frame: 24 months
Cmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
24 months
Cellular kinetics of Tisagenlecleucel (Tmax)
Time Frame: 24 months
Tmax cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
24 months
Cellular kinetics of Tisagenlecleucel (AUC)
Time Frame: 24 months
AUC cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
24 months
Cellular kinetics of Tisagenlecleucel (Clast)
Time Frame: 24 month
Clast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
24 month
Cellular kinetics of Tisagenlecleucel (Tlast)
Time Frame: 24 month
Tlast cellular kinetics parameter (via qPCR) for tisagenlecleucel in the presence of ibrutinib
24 month
Anti-drug antibody (ADA) response to Tisagenlecleucel (humoral immunogenicity)
Time Frame: 24 months
Pre-existing and treatment related immunogenicity (humoral) of tisagenlecleucel will be characterized by flow cytometry
24 months
Anti- tisagenlecleucel t-cell response (cellular immunogenicity)
Time Frame: 24 months
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
Time Frame: 24 months
24 months
Characterize efficacy of tisagenlecleucel in the presence of ADA and/or anti-tisagenlecleucel t-cell response
Time Frame: 24 month
24 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 11, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 13, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 13, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 15, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 31, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 27, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings