Clinical trial NCT02902965: Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed/Relapsed and Refractory Multiple Myeloma
Official title: An Open-label Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Bruton's Tyrosine Kinase
Bortezomib
Dexamethasone
Ibrutinib
Lead sponsor: Pharmacyclics Switzerland GmbH
Sponsor class: INDUSTRY
Collaborators: name: Janssen Research & Development, LLC
First posted: 2016-09-16
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Subjects with multiple myeloma (MM) who have received 1-3 prior lines of therapy and have demonstrated disease progression since the completion of the most recent treatment regimen. (Subjects may have received prior bortezomib exposure if it does not meet the exclusion criteria for prior proteasome inhibitor use)
* Measurable disease defined by at least one of the following:

  * Serum monoclonal protein (SPEP) ≥1 g/dL (for subjects with immunoglobulin A (IgA), immunoglobulin D (IgD), immunoglobulin E (IgE) or immunoglobulin M (IgM) multiple myeloma SPEP ≥0.5 g/dL)
  * Urine monoclonal protein (UPEP) ≥200 mg by 24 hour urine electrophoresis
* Adequate hematologic, hepatic and renal function
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤2

Exclusion Criteria:

* Subject must not have primary refractory disease
* Refractory or non-responsive to prior proteasome inhibitor (PI) therapy (bortezomib or carfilzomib)
* Peripheral neuropathy Grade ≥2 or Grade 1 with pain at Screening
* Plasma cell leukemia, primary amyloidosis, or POEMS syndrome
* Unable to swallow capsules or disease significantly affecting gastrointestinal function
* Requires treatment with strong CYP3A inhibitors
* Women who are pregnant or breast feeding

Primary outcomes:
measure: Median Progression-Free Survival (PFS)
timeFrame: 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.
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 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.
measure: Progression Free Survival (PFS) at Landmark Points - 20 Months
timeFrame: 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.
measure: Duration of Response (DOR)
timeFrame: The median time on study was 19.6 months (range: 0.16+, 24.64).
measure: Overall Survival (OS) at 24 Months
timeFrame: 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.
measure: Time to Progression (TTP)
timeFrame: The median time on study was 19.6 months (range: 0.16+, 24.64).
measure: Safety and Tolerability of Ibrutinib in Combination With Bortezomib and Dexamethasone as Measured by the Number of Participants With Adverse Events.
timeFrame: 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).
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno
city: Nový Hradec Králové
country: Czechia
facility: Fakultní nemocnice Hradec Králové
city: Ostrava-Poruba
country: Czechia
facility: Fakultní nemocnice Ostrava
city: Praha 2
country: Czechia
facility: Všeobecná fakultní nemocnice v Praha
city: Berlin
country: Germany
facility: Helios-Kliniken Berlin-Buch
city: Berlin
country: Germany
facility: Vivantes Klinikum Spandau
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: München
country: Germany
facility: Klinikum der Universität München Campus Grosshadern
city: Athens
country: Greece
facility: 251 General Air Force Hospital
city: Athens
country: Greece
facility: General Hospital of Athens "Alexandra"
city: Athens
country: Greece
facility: General Hospital of Athens "Evangelismos"
city: Athens
country: Greece
facility: General Hospital of Athens "LAIKO"
city: Patras
country: Greece
facility: University General Hospital of Patra
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki "G. Papanikolau"
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo della Sofferenza
state: Foggia
city: Bologna
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
city: Meldola (FC)
country: Italy
facility: Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci
city: Rimini
country: Italy
facility: Ospedale degli Infermi
city: Terni
country: Italy
facility: Azienda Ospedaliera S. Maria di Terni
city: Mostoles
country: Spain
facility: Hospital Universitario Rey Juan Carlos
state: Madrid
city: A Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Badalona
country: Spain
facility: ICO Badalona-Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medicine Faculty
city: Kayseri
country: Turkey
facility: Erciyes University Medical Faculty
city: Samsun
country: Turkey
facility: Ondokuz Mayis Univ. Med. Fac.
Study officials:
affiliation: Pharmacyclics Switzerland GmbH
name: Bernhard Hauns, MD
role: STUDY_DIRECTOR
References: