Phase 3
Completed N=523
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
Mantle Cell Lymphoma
Source: ClinicalTrials.gov NCT01776840 ↗
Enrolled (actual)
523
Serious AEs
69.0%
Results posted
Jul 2022
Primary outcomePrimary: Progression-free Survival (PFS) — 52.9; 80.6 months — p=0.011
◆ Published Evidence
Highly cited
210citations · ~53 / year
Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma.
Summary
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.
Linked Publications
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Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) |
52.9; 80.6 | 0.011 sig |
| SECONDARY Overall Survival |
95.9; 104.3 | — |
| SECONDARY Complete Response Rate |
57.6; 65.5 | — |
| SECONDARY Time-to-Next Treatment |
92.0; NA | — |
| SECONDARY Percentage of Participants With Overall Response |
88.5; 89.7 | — |
| SECONDARY Minimal Residual Disease (MRD)-Negative Response Rate |
56.5; 62.1 | — |
| SECONDARY Time to Worsening (TTW) in the Lymphoma (Lym) Subscale of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Questionnaire |
22.2; 17.4 | — |
| SECONDARY Duration of Response (DoR) |
63.5; 81 | — |
| SECONDARY Duration of Complete Response (DoCR) |
78.1; NA | — |
| SECONDARY Time to Response |
2.79; 2.79 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
257; 259 | — |
| SECONDARY Oral Plasma Clearance (CL/F) of Ibrutinib |
1123 | — |
| SECONDARY Oral Volume of Distribution at Steady State of Ibrutinib |
7286 | — |
| SECONDARY Area Under the Concentration Curve of Ibrutinib During 24 Hours After Dosing at Steady State |
425 | — |
| SECONDARY Minimum Observed Plasma Concentration of Ibrutinib |
3.90 | — |
| SECONDARY Maximum Observed Plasma Concentration of Ibrutinib |
74.5 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of mantle cell lymphoma (MCL) reviewed and approved by central laboratory: diagnosis must include morphology and expression of either cyclin D1 in association with other relevant markers (eg, CD19, CD20, PAX5 and CD5) or evidence of t(11;14) as assessed by cytogenetics, fluorescent in situ hybridization (FISH), or polymerase chain reaction (PCR)
- Clinical Stage II, III, or IV by Ann Arbor Classification
- At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
- No prior therapies for MCL
- Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
- Hematology and biochemical laboratory values within protocol-defined limits
- Agrees to protocol-defined use of effective contraception
- Negative blood or urine pregnancy test at screening
Exclusion Criteria
- Major surgery within 4 weeks of random assignment
- Known central nervous system lymphoma
- Diagnosed or treated for malignancy other than MCL, except: malignancy treated with curative intent and with no known active disease present for >=3 years before random assignment; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated cervical carcinoma in situ without evidence of disease
- Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant
- History of stroke or intracranial hemorrhage within 6 months prior to random assignment
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists
- Requires treatment with strong CYP3A inhibitors
- Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
- Vaccinated with live, attenuated vaccines within 4 weeks of random assignment
- Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antibiotics
- Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
Data sourced from ClinicalTrials.gov (NCT01776840) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.