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Diffuse Large B-cell LymphomaPhase 1NCT03876028

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

A Phase 1 study testing Tisagenlecleucel and Ibrutinib in people with Diffuse Large B-cell Lymphoma, run by Novartis Pharmaceuticals at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diffuse Large B-cell Lymphoma
What is being tested?
Tisagenlecleucel and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
2 sitesUnited States
Study dates
11 Jun 2019to 1 Nov 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 9Show fewer
  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Pennsylvania, Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

  • H Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida, 33612

Other trials in United States

About this study

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

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.

Being tested
Tisagenlecleucel, Ibrutinib
Keywords
Lymphoma, Diffuse Large B-cell lymphoma, DLBCL, r/r Diffuse Large B-cell Lymphoma, relapsed/refractory DLBCL, CTL019, Tisagenlecleucel, Ibrutinib
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TisagenlecleucelBiological

    Infusion

  • IbrutinibDrug

    Oral (tablets or capsules)

Study groups in NCT03876028
Study groupRoleWhat they receive
Ibrutinib (before leukapheresis) + TisagenlecleucelExperimentalPatients will start ibrutinib treatment before leukapheresis
Receives: Biological: Tisagenlecleucel; Drug: Ibrutinib
Ibrutinib (after leukapheresis) + TisagenlecleucelExperimentalPatients will start ibrutinib treatment after leukapheresis.
Receives: Biological: Tisagenlecleucel; Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Month 24 is planned study end

    Measured: 24 months

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

    Month 24 is planned study end

    Measured: 24 months

  3. Ibrutinib dose modification following tisagenlecleucel infusion

    Month 24 is planned study end

    Measured: 24 months

Secondary outcomes (16)

  1. Response Rate

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

    Measured: Month 3

  2. Response Rate

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

    Measured: Month 6

  3. Overall Response Rate

    Measured: 24 months

  4. Duration of Response

    Measured: 24 months

  5. Progression Free Survival (PFS)

    Measured: 24 months

  6. Overall Survival (OS)

    Measured: 24 months

  7. 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.

    Measured: 24 months

  8. Cellular kinetics of Tisagenlecleucel (Cmax)

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

    Measured: 24 months

  9. Cellular kinetics of Tisagenlecleucel (Tmax)

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

    Measured: 24 months

  10. Cellular kinetics of Tisagenlecleucel (AUC)

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

    Measured: 24 months

  11. Cellular kinetics of Tisagenlecleucel (Clast)

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

    Measured: 24 month

  12. Cellular kinetics of Tisagenlecleucel (Tlast)

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

    Measured: 24 month

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

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

    Measured: 24 months

  14. 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

    Measured: 24 months

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

    Measured: 24 months

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

    Measured: 24 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2019
  2. Study start11 Jun 2019
  3. Primary completion1 Nov 2021
  4. Study completion1 Nov 2021

Why it stopped: Business reasons

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Parallel groups
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)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03876028
Sponsor's protocol ID
CCTL019L12101C
Status last verified
Jan 2023
First submitted
13 Mar 2019
Last updated
31 Jan 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Chavez JC, Napier E, Bondanza A, Lewandowski A, Mataraza J, Quinn D, Kwon P, Locke FL, Engels B, Awasthi R, Georgala P, Leyk M, Hynds D, Moschetta M, Schuster SJ. Tisagenlecleucel in combination with ibrutinib in adults with relapsed and/or refractory large B-cell lymphomas. Blood Neoplasia. 2025 Oct 24;3(1):100176. doi: 10.1016/j.bneo.2025.100176. eCollection 2026 Feb.

    PubMed 41536778

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tisagenlecleucel and Ibrutinib in people with Diffuse Large B-cell Lymphoma, run by Novartis Pharmaceuticals at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Business reasons). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (AEs) and serious adverse events (SAEs) (time frame: 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03876028, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2023.

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