Multiple MyelomaPhase 2NCT02902965
Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed/Relapsed and Refractory Multiple Myeloma
A Phase 2 study testing Ibrutinib, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Pharmacyclics Switzerland GmbH at 33 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Ibrutinib, Bortezomib and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 74 participants
- Where
- 33 sitesin 6 countries
- Study dates
- 20 Sep 2016to 26 Oct 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
33 sites in 6 countries.
33 sites in 6 countries
Spain9 sites
Complejo Hospitalario Universitario A Coruña
A Coruña
ICO Badalona-Hospital Germans Trias i Pujol
Badalona
Hospital Clínic i Provincial de Barcelona
Barcelona
Hospital Universitario Madrid Sanchinarro
Madrid
Hospital Universitario Rey Juan Carlos
Móstoles, Madrid
Clinica Universidad de Navarra
Pamplona
Hospital Universitario de Salamanca
Salamanca
Hospital Universitario Virgen del Rocio
Seville
Hospital Universitario Dr. Peset
Valencia
Greece6 sites
251 General Air Force Hospital
Athens
General Hospital of Athens "Alexandra"
Athens
General Hospital of Athens "Evangelismos"
Athens
General Hospital of Athens "LAIKO"
Athens
University General Hospital of Patra
Pátrai
General Hospital of Thessaloniki "G. Papanikolau"
Thessaloniki
Italy6 sites
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
Bologna
Istituto Scientifico Romagnolo Per lo Studio e la Cura dei Tumori
Meldola (FC)
Ospedale Santa Maria delle Croci
Ravenna
Ospedale degli Infermi
Rimini
IRCCS Ospedale Casa Sollievo della Sofferenza
San Giovanni Rotondo, Foggia
Azienda Ospedaliera S. Maria di Terni
Terni
Czechia4 sites
Fakultní nemocnice Brno
Brno
Fakultní nemocnice Hradec Králové
Nový Hradec Králové
Fakultní nemocnice Ostrava
Ostrava-Poruba
Všeobecná fakultní nemocnice v Praha
Prague
Germany4 sites
Helios-Kliniken Berlin-Buch
Berlin
Vivantes Klinikum Spandau
Berlin
Universitätsklinikum Jena
Jena
Klinikum der Universität München Campus Grosshadern
München
Turkey (Türkiye)4 sites
Ankara University Medical Faculty
Ankara
Dokuz Eylul University Medicine Faculty
Izmir
Erciyes University Medical Faculty
Kayseri
Ondokuz Mayis Univ. Med. Fac.
Samsun
About this study
Official title: An Open-label Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- Ibrutinib, Bortezomib, Dexamethasone
- Keywords
- Bruton's Tyrosine Kinase, Bortezomib, Dexamethasone, Ibrutinib
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called Imbruvica
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
BortezomibDrug
Also called Velcade
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
DexamethasoneDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Ibrutinib+ Bortezomib+ Dexamethasone | Experimental | Not described Receives: Drug: Ibrutinib; Drug: Bortezomib; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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)
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.
Measured: 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
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2016 (estimated)
- Study start20 Sep 2016
- Primary completion26 Oct 2018
- Study completion26 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 74 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmacyclics Switzerland GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Janssen Research & Development, LLC
- Responsible party
- Sponsor
- Investigators
- Bernhard Hauns, MD, Study director, Pharmacyclics Switzerland GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02902965
- Sponsor's protocol ID
- PCYC-1139-CA
- Status last verified
- Mar 2020
- First submitted
- 19 Aug 2016
- Last updated
- 16 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Study of Ibrutinib in Combination With Bortezomib and Dexamethasone in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02902965
- Acronym / sponsor ID
- PCYC-1139-CA
- Conditions
- Multiple Myeloma
- Keywords
- Bruton's Tyrosine Kinase, Bortezomib, Dexamethasone, Ibrutinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 74 participants (actual)
- Lead sponsor
- Pharmacyclics Switzerland GmbHIndustry (pharma, biotech, devices)
- Collaborators
- Janssen Research & Development, LLC
- Study start
- 20 Sep 2016 (actual)
- Primary completion
- 26 Oct 2018 (actual)
- Study completion
- 26 Oct 2018 (actual)
- First posted
- 16 Sep 2016 (estimated)
- Results
- Posted 2 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib+ Bortezomib+ Dexamethasone | Experimental | Drug: Ibrutinib, Drug: Bortezomib, Drug: Dexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
- Adequate hematologic, hepatic and renal function
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IbrutinibAlso: ImbruvicaIbrutinib 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 | Drug | Ibrutinib+ Bortezomib+ Dexamethasone |
| BortezomibAlso: VelcadeCycles 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 | Drug | Ibrutinib+ Bortezomib+ Dexamethasone |
| DexamethasoneCycles 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. | Drug | Ibrutinib+ Bortezomib+ Dexamethasone |
Primary outcome
Median Progression-Free Survival (PFS)
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.
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.
6 secondary outcomes
Overall Response Rate (ORR)
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
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)
Time frame: The median time on study was 19.6 months (range: 0.16+, 24.64).
Overall Survival (OS) at 24 Months
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.
Time to Progression (TTP)
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.
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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bernhard Hauns, MD study director
Pharmacyclics Switzerland GmbH
33 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ibrutinib, Bortezomib and Dexamethasone in people with Multiple Myeloma, run by Pharmacyclics Switzerland GmbH at 33 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in Spain, Greece, Italy, Czechia, Germany and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Progression-Free Survival (PFS) (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2020.