Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed/Relapsed and Refractory Multiple Myeloma

NCT02902965 | Completed Phase 2 Results

• 1 other identifier: PCYC-1139-CA
• Study Type: interventional
• Target: 74
• Locations: 6 countries
• Sites: 33

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.

Conditions

Multiple Myeloma

Keywords

Bruton's Tyrosine Kinase; Bortezomib; Dexamethasone; Ibrutinib

Outcome Measures

Primary Outcomes (1)

• 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.

  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 (6)

• Overall Response Rate (ORR)

  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

  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 median time on study was 19.6 months (range: 0.16+, 24.64).

• Overall Survival (OS) at 24 Months

  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.

• Time to Progression (TTP)

  The median time on study was 19.6 months (range: 0.16+, 24.64).

Study Arms (1)

Ibrutinib+ Bortezomib+ Dexamethasone

EXPERIMENTAL

Drug: Ibrutinib; Drug: Bortezomib; Drug: Dexamethasone

Interventions

Ibrutinib DRUG

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

Also known as: Imbruvica

Ibrutinib+ Bortezomib+ Dexamethasone

Bortezomib DRUG

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

Also known as: Velcade

Ibrutinib+ Bortezomib+ Dexamethasone

Dexamethasone DRUG

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.

Ibrutinib+ Bortezomib+ Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Pharmacyclics Switzerland GmbH: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (33)

Fakultní nemocnice Brno

Brno, Czechia

Location

Fakultní nemocnice Hradec Králové

Nový Hradec Králové, Czechia

Location

Fakultní nemocnice Ostrava

Ostrava-Poruba, Czechia

Location

Všeobecná fakultní nemocnice v Praha

Prague, Czechia

Location

Helios-Kliniken Berlin-Buch

Berlin, Germany

Location

Vivantes Klinikum Spandau

Berlin, Germany

Location

Universitätsklinikum Jena

Jena, Germany

Location

Klinikum der Universität München Campus Grosshadern

München, Germany

Location

251 General Air Force Hospital

Athens, Greece

Location

General Hospital of Athens "Alexandra"

Athens, Greece

Location

General Hospital of Athens "Evangelismos"

Athens, Greece

Location

General Hospital of Athens "LAIKO"

Athens, Greece

Location

University General Hospital of Patra

Pátrai, Greece

Location

General Hospital of Thessaloniki "G. Papanikolau"

Thessaloniki, Greece

Location

IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, Foggia, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, Italy

Location

Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori

Meldola (FC), Italy

Location

Ospedale Santa Maria delle Croci

Ravenna, Italy

Location

Ospedale degli Infermi

Rimini, Italy

Location

Azienda Ospedaliera S. Maria di Terni

Terni, Italy

Location

Hospital Universitario Rey Juan Carlos

Móstoles, Madrid, Spain

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, Spain

Location

ICO Badalona-Hospital Germans Trias i Pujol

Badalona, Spain

Location

Hospital Clínic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, Spain

Location

Clinica Universidad de Navarra

Pamplona, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Hospital Universitario Dr. Peset

Valencia, Spain

Location

Ankara University Medical Faculty

Ankara, Turkey (Türkiye)

Location

Dokuz Eylul University Medicine Faculty

Izmir, Turkey (Türkiye)

Location

Erciyes University Medical Faculty

Kayseri, Turkey (Türkiye)

Location

Ondokuz Mayis Univ. Med. Fac.

Samsun, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ibrutinib; Bortezomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Dr. Bernhard Hauns, Medical Monitor
• Organization: Pharmacyclics Switzerland GmbH

bhauns@pcyc.com

+41 52 556 0800

Study Officials

• Bernhard Hauns, MD

  Pharmacyclics Switzerland GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2016
• First Posted: September 16, 2016
• Study Start: September 20, 2016
• Primary Completion: October 26, 2018
• Study Completion: October 26, 2018
• Last Updated: March 16, 2020
• Results First Posted: January 2, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (9); TU (4); DE (4); IT (6); GR (6); CZ (4)