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
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ClinicalTrials.gov Identifier: NCT01776840 |
Recruitment Status :
Active, not recruiting
First Posted : January 28, 2013
Results First Posted : July 26, 2022
Last Update Posted : April 25, 2024
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Sponsor:
Janssen Research & Development, LLC
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Janssen Research & Development, LLC
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Tracking Information | ||||
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First Submitted Date ICMJE | January 24, 2013 | |||
First Posted Date ICMJE | January 28, 2013 | |||
Results First Submitted Date ICMJE | June 30, 2022 | |||
Results First Posted Date ICMJE | July 26, 2022 | |||
Last Update Posted Date | April 25, 2024 | |||
Actual Study Start Date ICMJE | May 16, 2013 | |||
Actual Primary Completion Date | June 30, 2021 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Progression-free Survival (PFS) [ Time Frame: Up to 97 months ] Progression-free survival (PFS) is 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 is first reported. Disease assessments were based on the 2007 Revised Response Criteria for Malignant Lymphoma. PD is 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 diameter of previously identified node 1 cm in short axis).
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Original Primary Outcome Measures ICMJE |
Progression-free survival [ Time Frame: Up to the end-of-study visit until 265 progression-free survival events have been observed (up to 7 years after the last patient is randomized) ] | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | 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 | |||
Official Title ICMJE | A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, PCI-32765 (Ibrutinib), in Combination With Bendamustine and Rituximab (BR) in Subjects With Newly Diagnosed Mantle Cell Lymphoma | |||
Brief 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. | |||
Detailed Description | This is a randomized (individuals assigned to study treatment by chance), double blind (neither physician nor participant knows the treatment that the participant receives), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study to compare the efficacy and safety of ibrutinib given in combination with bendamustine and rituximab (BR) with BR alone in participants newly diagnosed with mantle cell lymphoma (MCL) who are 65 years of age or older. Approximately 520 participants will be randomly assigned in a 1:1 ratio and stratified by simplified Mantle Cell Lymphoma International Prognostic Index (MIPI) score (low risk [0-3] versus intermediate risk [4-5] versus high risk [6-11]). The treatment phase will extend from randomization until discontinuation of all study treatment or the clinical cutoff for the end of study. A cycle is defined as 28 days. All participants will receive open-label (identity of assigned study drug will be known) BR background therapy for a maximum of 6 cycles; participants with a complete response or partial response will continue to receive open-label background therapy with rituximab maintenance every second cycle for a maximum of 12 additional doses. In addition to the background therapy, all participants will receive blinded study drug (ibrutinib or placebo). Participants randomized to treatment Arm A will receive placebo capsules and participants randomized to treatment Arm B will receive ibrutinib capsules. Study drug will be administered daily and continuously until disease progression, unacceptable toxicity, or study end. Participants with stable disease after initial chemoimmunotherapy (BR+ibrutinib/placebo) should continue treatment with ibrutinib/placebo until disease progression, unacceptable toxicity, or study end. Participants with progressive disease must discontinue all study treatment. For participants who discontinue background therapy and do not have progressive disease, treatment with study drug will continue until disease progression or unacceptable toxicity or the clinical cutoff for the final analysis of progression-free survival (PFS). Participants receiving BR, rituximab, or ibrutinib at the clinical cutoff for the final analysis of PFS will continue open-label treatment until disease progression or unacceptable toxicity. Placebo will be stopped when the study is unblinded for the clinical cutoff for the final analysis of PFS. The posttreatment follow-up phase will begin once a participant discontinues bendamustine and rituximab and study drug. Participants who discontinue for reasons other than disease progression must continue to have disease evaluations as outlined in the protocol. Participants who discontinue due to disease progression will be followed for survival and subsequent anti-MCL therapy. The posttreatment follow-up phase will continue until death, lost to follow up, consent withdrawal, or study end, whichever occurs first. Four clinical cutoffs are planned. The first 3 clinical cutoffs will occur when approximately 134, 180, and 265 PFS events have been observed, respectively. The interim analyses and the final analysis of PFS will take place at these 3 clinical cutoffs, respectively; participant treatment assignment will be unblinded and placebo treatment will be stopped at the clinical cutoff for the final analysis of PFS. Treatment unblinding and stopping of placebo treatment could occur before the planned final analysis of PFS if recommended by the independent Data Monitoring Committee (DMC) after an interim analysis. The last cutoff will occur at the end of study, when 60% of the randomized participants have died or the Sponsor terminates the study, whichever comes first. Efficacy assessments will be conducted in accordance with the Revised Response Criteria for Malignant Lymphoma. Safety will be monitored throughout the study and summarized. Blood samples will be drawn for assessment of pharmacokinetic parameters. Blood and bone marrow will be collected for assessment of minimal residual disease and biomarker studies. | |||
Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 3 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Triple (Participant, Care Provider, Investigator) Primary Purpose: Treatment |
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Condition ICMJE | Mantle Cell Lymphoma | |||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Wang ML, Jurczak W, Jerkeman M, Trotman J, Zinzani PL, Belada D, Boccomini C, Flinn IW, Giri P, Goy A, Hamlin PA, Hermine O, Hernandez-Rivas JA, Hong X, Kim SJ, Lewis D, Mishima Y, Ozcan M, Perini GF, Pocock C, Song Y, Spurgeon SE, Storring JM, Walewski J, Zhu J, Qin R, Henninger T, Deshpande S, Howes A, Le Gouill S, Dreyling M; SHINE Investigators. Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma. N Engl J Med. 2022 Jun 30;386(26):2482-2494. doi: 10.1056/NEJMoa2201817. Epub 2022 Jun 3. | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Active, not recruiting | |||
Actual Enrollment ICMJE |
523 | |||
Original Estimated Enrollment ICMJE |
520 | |||
Estimated Study Completion Date ICMJE | May 15, 2024 | |||
Actual Primary Completion Date | June 30, 2021 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 65 Years and older (Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, Ireland, Israel, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Puerto Rico, Russian Federation, Slovakia, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States | |||
Removed Location Countries | Chile, Colombia, Czech Republic, Hong Kong, Peru, Portugal, Singapore | |||
Administrative Information | ||||
NCT Number ICMJE | NCT01776840 | |||
Other Study ID Numbers ICMJE | CR100967 PCI-32765MCL3002 ( Other Identifier: Janssen Research & Development, LLC ) U1111-1137-0389 ( Other Identifier: Universal Trial Number ) 2012-004056-11 ( EudraCT Number ) |
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Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | Janssen Research & Development, LLC | |||
Original Responsible Party | Same as current | |||
Current Study Sponsor ICMJE | Janssen Research & Development, LLC | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE | Pharmacyclics LLC. | |||
Investigators ICMJE |
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PRS Account | Janssen Research & Development, LLC | |||
Verification Date | April 2024 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |