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

NCT03876028 | Terminated Phase 1 FDA Drug

• 1 other identifier: CCTL019L12101C
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (16)

• Response Rate

  Month 3

• Response Rate

  Month 6

• Overall Response Rate

  24 months

• Duration of Response

  24 months

• Progression Free Survival (PFS)

  24 months

Study Arms (2)

Ibrutinib (before leukapheresis) + Tisagenlecleucel

EXPERIMENTAL

Patients will start ibrutinib treatment before leukapheresis

Biological: Tisagenlecleucel; Drug: Ibrutinib

Ibrutinib (after leukapheresis) + Tisagenlecleucel

EXPERIMENTAL

Patients will start ibrutinib treatment after leukapheresis.

Biological: Tisagenlecleucel; Drug: Ibrutinib

Interventions

Tisagenlecleucel BIOLOGICAL

Infusion

Ibrutinib (after leukapheresis) + Tisagenlecleucel; Ibrutinib (before leukapheresis) + Tisagenlecleucel

Ibrutinib DRUG

Oral (tablets or capsules)

Ibrutinib (after leukapheresis) + Tisagenlecleucel; Ibrutinib (before leukapheresis) + Tisagenlecleucel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• 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.

  PMID: 41536778 DERIVED

Related Links

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

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma; Recurrence

Interventions

tisagenlecleucel; ibrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: "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."

Study Record Dates

• First Submitted: March 13, 2019
• First Posted: March 15, 2019
• Study Start: June 11, 2019
• Primary Completion: November 1, 2021
• Study Completion: November 1, 2021
• Last Updated: January 31, 2023

Record last verified: 2023-01

Locations

US (2)