This is a Phase 2 open-label study to evaluate the efficacy and safety of ibrutinib in combination with bortezomib and dexamethasone for patients with relapsed or relapsed and refractory multiple myeloma.
Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoeitic cells other than T cells and is necessary for downstream signal transduction from various hematopoietic receptors including the B cell receptor as well as some Fc, chemokine and adhesion receptors, and is crucial for both B cell development and osteoclastogenesis. Although down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from many myeloma patients and some cell lines. Ibrutinib is a potent and specific inhibitor of Btk currently in Phase 2 and 3 clinical trials. The current study is designed and intended to determine the safety and efficacy of ibrutinib in combination with bortezomib and dexamethasone in subjects with relapsed/relapsed and refractory multiple myeloma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
74
Ibrutinib 840 mg orally, once daily continuously starting day 1 of cycle 1 until confirmed disease progression, unacceptable toxicity or other protocol specified reason for discontinuation
Cycles 1-8: (21-day cycle): Bortezomib 1.3 mg/m\^2 sub-cutaneously on days 1, 4, 8, and 11 of each Cycle Cycles 9-12: (42-day cycle): Bortezomib 1.3 mg/m\^2 sub-cutaneously on days 1, 8, 22 and 29 of each Cycle
Cycles 1-8: (21-day cycle): Dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11 and 12 of each cycle Cycles 9-12: (42-day cycle): Dexamethasone 20 mg orally on days 1, 2, 8, 9, 22, 23, 29 and 30 of each cycle Cycles 13+ (28-day cycle): Dexamethasone 40 mg orally once weekly Dose adjustment of dexamethasone to 10 mg on days specified during cycles 1-12 and 20 mg weekly during cycles 13+ is recommended for subjects \>75 years of age. Following implementation of Protocol Amendment 4, dexamethasone administration was reduced to Days 1, 4, 8 and 11 during each 21-day cycle (Cycles 1-8) and on Days 1, 8, 22, 29 on each 42-day cycle (Cycles 9-12) and unchanged thereafter.
Median Progression-Free Survival (PFS)
The primary efficacy endpoint of this study is mPFS. Progression free survival is defined as the time from the date of first dose of study treatment to confirmed disease progression or death from any cause, whichever occurs first.
Time frame: The median time on study was 19.6 months (range: 0.16+, 24.64). Participants were evaluated for Progression-Free Survival (PFS) during their entire time on the study.
Overall Response Rate (ORR)
Overall Response Rate is the percentage of participants who achieve a PR or better over the course of the study but prior to initiation of subsequent anti-cancer therapy
Time frame: The median time on study was 19.6 months (range: 0.16+, 24.64). Participants were evaluated for Overall Response (OR) during the entire time on the study.
Progression Free Survival (PFS) at Landmark Points - 20 Months
PFS at landmark points are the percentage of participants without progression (i.e., KM estimates) at the landmark time endpoints.
Time frame: The median time on study was 19.6 months (range: 0.16+, 24.64), with the 20 month Progression-Free Survival (PFS) rate presented based on Kaplan-Meier estimates.
Duration of Response (DOR)
The time interval between the date of initial documentation of a response (PR or better) and the date of first documented evidence of PD, death, or date of censoring for the participants not progressed/died. The censoring date is the last adequate tumor assessment date.
Time frame: The median time on study was 19.6 months (range: 0.16+, 24.64).
Overall Survival (OS) at 24 Months
As the median overall survival has not been reached, the data for the landmark analysis at 24 months are provided.
Time frame: The median time on study was 19.6 months (0.16+, 24.64), with the 24 month Overall Survival (OS) rate presented based on Kaplan-Meier estimates.
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Fakultní nemocnice Brno
Brno, Czechia
Fakultní nemocnice Hradec Králové
Nový Hradec Králové, Czechia
Fakultní nemocnice Ostrava
Ostrava-Poruba, Czechia
Všeobecná fakultní nemocnice v Praha
Prague, Czechia
Helios-Kliniken Berlin-Buch
Berlin, Germany
Vivantes Klinikum Spandau
Berlin, Germany
Universitätsklinikum Jena
Jena, Germany
Klinikum der Universität München Campus Grosshadern
München, Germany
251 General Air Force Hospital
Athens, Greece
General Hospital of Athens "Alexandra"
Athens, Greece
...and 23 more locations
Time to Progression (TTP)
Time from date of first dose of study treatment to the date of first documented evidence of PD or date of censoring for the participants not progressed. The censoring date is the last adequate tumor assessment date.
Time frame: The median time on study was 19.6 months (range: 0.16+, 24.64).
Safety and Tolerability of Ibrutinib in Combination With Bortezomib and Dexamethasone as Measured by the Number of Participants With Adverse Events.
Safety and tolerability of ibrutinib in combination with bortezomib and dexamethasone as measured by the frequency and type of adverse events graded using the NCI CTCAE v 4.03. Frequency and Type of Adverse Events are reported in the Adverse Events module
Time frame: From first dose of Ibrutinib to within 30 days of last dose for each participant or until study closure. This is the median treatment duration for Ibrutinib of 5.7 months (range: 0.1 - 23.7 months) +30 days (Adverse Events collection period).