A Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib Given in Combination With Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma
CompletedPhase 3Results postedLast updated 8 July 2025
What this trial tests
Phase 3 trial testing Bendamustine in Mantle Cell Lymphoma in 523 participants. Completed in 24 June 2024.
65 and older, any sex, with Mantle Cell Lymphoma. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Progression-free Survival (PFS)Primary· Up to 97 months
Progression-free survival (PFS) was defined as the interval between the date of randomization to the date of disease progression (PD) or relapse from complete response (CR) or death, whichever was first reported. Disease assessments were based on the 2007 Revised Response Criteria for Malignant Lymphoma. PD was defined as any new lesion or increase by 50 percent (%) of previously involved sites from nadir (PD criteria: Appearance of new nodal lesion 1.5 centimeters \[cm\] in any axis, 50% increase in sum of product of diameters \[SPD\] of greater than \[\>\] 1 node or 50% increase in longest d
Group
Value
95% CI
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
52.9
43.7 – 71.0
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
80.6
61.9 – NA
Overall SurvivalSecondary· From randomization (Day -3) up to 121 months
Overall survival was defined as the time from the date of randomization to the date of the participant's death. Kaplan-Meier estimate was used.
Group
Value
95% CI
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
95.9
86.1 – 115.3
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
104.3
81.1 – NA
Complete Response RateSecondary· Up to 97 months
Complete response (CR) rate was defined as the percentage of participants who achieve CR (based on investigator assessment) on or prior to the initiation of subsequent anticancer therapy. Criteria for CR: disappearance of all evidence of disease; mass of any size permitted if positron emission tomography (PET) negative; regression to normal size on computed tomography (CT); spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy.
Group
Value
95% CI
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
57.6
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
65.5
Time-to-Next TreatmentSecondary· Up to 97 months
Time-to-next treatment was measured from the date of randomization to the start date of any anti-mantle cell lymphoma (anti-MCL) treatment subsequent to the study treatment.
Group
Value
95% CI
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
92.0
71.5 – NA
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
NA
NA – NA
Percentage of Participants With Overall ResponseSecondary· Up to 97 months
Percentage of participants with overall response was defined as the portion of participants who achieved CR or PR. Criteria for CR: disappearance of all evidence of disease; mass of any size permitted if PET negative; regression to normal size on CT; spleen and liver: not palpable, nodules disappeared; bone marrow: infiltrate cleared on repeat biopsy. Criteria for PR: greater than or equal to (\>=) 50% decrease in sum of the diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions.
Group
Value
95% CI
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
88.5
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
89.7
Minimal Residual Disease (MRD)-Negative Response RateSecondary· Up to 97 months
Minimal residual disease negative rate was defined as the percentage of participants with a best overall response of CR with MRD-negative disease status (that is, \<5 mantle cell lymphoma \[MCL\] cell per 10,000 leukocytes for detection using the MRD assay), as assessed by flow cytometry of a bone marrow and/or peripheral blood sample.
Group
Value
95% CI
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
56.5
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
62.1
Time to Worsening (TTW) in the Lymphoma (Lym) Subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) QuestionnaireSecondary· Up to 97 months
Time to worsening in the Lymphoma subscale of the FACT-Lym, defined as the interval from the date of randomization to the start date of worsening of participant symptoms. Worsening was defined by a 5-point decrease from baseline, death, or a missing assessment due to being "too ill", whichever occurred first. FACT-Lym Lymphoma subscale contains 15 questions, scores from 0 to 4 for each question (higher the worse). Lymphoma subscale score was the total of reverse scores, ranged 0 to 60. Higher scores indicated a better quality of life.
Group
Value
95% CI
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
22.2
9.3 – 34.0
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
17.4
8.3 – 27.6
Duration of Response (DoR)Secondary· Up to 97 months
Duration of Response (DoR) was defined as the interval between the date of initial documentation of a response including PR and the date of first documented evidence of PD or death
Group
Value
95% CI
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
63.5
47 – 76.9
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
81
64.2 – NA
Duration of Complete Response (DoCR)Secondary· Up to 97 months
Duration of complete response (DoCR) was defined as the interval between the date of initial documentation of a CR and the date of first documented evidence of PD or death whichever occurs first.
Group
Value
95% CI
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
78.1
65.6 – NA
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
NA
81.7 – NA
Time to ResponseSecondary· Up to 97 months
Time to response was defined as the interval between the date of randomization and the date of initial documentation of a response.
Group
Value
95% CI
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
2.79
1.9 – 11.2
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
2.79
2.1 – 10.1
Number of Participants With Treatment-emergent Adverse Events (TEAEs)Secondary· Placebo + BR (Treatment A): From first dose of study treatment (Day 1) up to 100.1 months; Ibrutinib + BR (Treatment B): From first dose of study treatment (Day 1) up to 117.2 months
Number of participants with TEAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. Treatment-emergent adverse events were defined as adverse events with onset or worsening on or after date of first dose of study treatment up to and including 30 days after date of last dose of study medication, or the initiation of subsequent anticancer therapy, whichever is earlier.
Group
Value
95% CI
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
257
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
259
Oral Plasma Clearance (CL/F) of IbrutinibSecondary· Pre-dose on Day 2 of Cycles 1, 2 and 3; and 1, 2 and 4 hours post-dose on Day 2 of Cycles 1 and 2
CL/F was defined as apparent total systemic clearance of ibrutinib after extravascular administration. Cl/F of Ibrutinib was determined using population pharmacokinetics (PopPK modeling).
Group
Value
95% CI
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
1123
± 4.83
Adverse events — posted to ClinicalTrials.gov
Time frame: All-cause mortality: From randomization (Day -3) up to 121 months; SAEs and Non SAEs: Placebo + BR (Treatment A): From first dose of study treatment (Day 1) up to 100.1 months; Ibrutinib + BR (Treatment B): From first dose of study treatment (Day 1) up to 117.2 months.
Reporting threshold: 5%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
Placebo + Bendamustine and Rituximab (BR) (Treatment A)
Serious: 157/260 (60%)
Deaths: 129/262
Ibrutinib + Bendamustine and Rituximab (BR) (Treatment B)
The purpose of this study is to evaluate the efficacy and safety of ibrutinib given in combination with bendamustine and rituximab in patients 65 years of age or older with newly diagnosed mantle cell lymphoma.
Publications & conference data
8 peer-reviewed publications reference this trial (live from Europe PMC):
NCT07225985 — Pralatrexate With Bendamustine and Total-Body Irradiation Followed by Donor Stem Cell Transplant for the Treatment of Re
· Phase 1, PHASE2
· not yet recruiting
NCT07189065 — A Study of Rocbrutinib in Participants With Relapse or Refractory Non-GCB Diffuse Large B-Cell Lymphoma
· Phase 2
· recruiting
NCT07169565 — Ibrutinib Followed by BR (Bendamustine and Rituximab) as a Time-Limited Therapy for Waldenström Macroglobulinemia
· Phase 1
· not yet recruiting
NCT06911502 — A Study to Compare the Efficacy and Safety of Golcadomide in Combination With Rituximab (Golca + R) vs Investigator's Ch
· Phase 3
· recruiting
NCT07003464 — Phase II Trial of Zanubrutinib, Obinutuzumab, Bendamustine (ZGB) as First-Line Therapy for Chronic Lymphocytic Leukemia:
· Phase 2
· not yet recruiting
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Currently open trials in the same condition.
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NCT06357676 — Glofitamab Plus Ibrutinib With Obinutuzumab for the Treatment of Patients With Mantle Cell Lymphoma, IGNITE MCL Trial
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NCT06854003 — BRAZAN: A Randomized Phase 2 Study of Bendamustine, Rituximab, Cytarabine (AraC) Induction With Zanubrutinib (BRAZAN) Fo
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Publications: Europe PMC API search by NCT ID, retrieved 9 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Janssen Research & Development, LLC
Last refreshed: 8 July 2025
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01776840.