Multiple MyelomaPhase 1/2NCT01962792
Study of BTK Inhibitor, Ibrutinib in Combination With Carfilzomib in Subjects With Relapsed and Refractory Multiple Myeloma
A Phase 1/2 study testing Ibrutinib, Carfilzomib and Dexamethasone in people with Multiple Myeloma, run by Pharmacyclics LLC. at 17 sites in 2 countries.
Trial summary
A MULTICENTER PHASE 1/2B STUDY OF THE BRUTON'S TYROSINE KINASE INHIBITOR, IBRUTINIB (PCI-32765), IN COMBINATION WITH CARFILZOMIB (KYPROLIS™) IN SUBJECTS 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, Carfilzomib and Dexamethasone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 17 sitesin 2 countries
- Study dates
- Dec 2013to Mar 2019
- Phase
- Phase 1/2
- 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
- Measurable disease of MM as defined by at least ONE of the following:
- Serum monoclonal protein (SPEP) ≥1 g/dL
- Urine M-protein ≥200 mg/24 hrs
- Serum free light chain (SFLC): involved FLC ≥10 mg/dL (≥100 mg/L) AND abnormal kappa to lambda serum free light chain ratio
- Relapsed or relapsed and refractory MM after receiving at least 2 previous therapies, including an immunomodulator and bortezomib and had either no response or documented disease progression (according to IMWG criteria) to the most recent treatment regimen
- Adequate hematologic, hepatic, and renal function
Show all 12Show fewer
- ECOG performance status of 0-2
- Must meet all inclusion criteria defined in main study and in addition the following criteria must be met:
- Subject must have received a regimen containing carfilzomib in combination with dexamethasone as their most recent line of therapy and have:
- Achieved less than a partial response (<PR) following at least 4 cycles and are without evidence of progression disease (PD).
- OR
- Disease progression following an initial confirmed response of MR or better to the combination (according to IMWG response criteria).
Who cannot join
- Subject must not have primary refractory disease
- Plasma cell leukemia, primary amyloidosis or POEMS syndrome
- Unable to swallow capsules or disease significantly affecting gastrointestinal function
- Requires anti-coagulation with warfarin or a vitamin K antagonist
- Requires treatment with strong CYP3A inhibitors
- Must not meet any exclusion criteria defined in main study except for exclusion criteria "Subject must not have primary refractory disease" which is related to prior carfilzomib
Trial locations and contacts
17 sites in 2 countries.
17 sites in 2 countries
United States16 sites
MUSC Hollings Cancer Center
Charleston, South Carolina, 29425
Carolinas Healthcare System
Charlotte, North Carolina, 28204
University of Cincinnati
Cincinnati, Ohio, 45267
Cleveland Clinic
Cleveland, Ohio, 44195
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Colorado Blood Cancer Institute
Denver, Colorado, 80218
City of Hope
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27705
University of California Los Angeles
Los Angeles, California, 90095
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232
New York Presbyterian Hospital - Weill-Cornell
New York, New York, 10021
Mount Sinai Hospital
New York, New York, 10029
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Virginia Commonwealth University
Richmond, Virginia, 23298
Methodist Healthcare System
San Antonio, Texas, 78229
About this study
Official title: A Multicenter Phase 1/2b Study of the Bruton's Tyrosine Kinase Inhibitor, Ibrutinib (PCI-32765), in Combination With Carfilzomib (Kyprolis™) in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
A MULTICENTER PHASE 1/2B STUDY OF THE BRUTON'S TYROSINE KINASE INHIBITOR, IBRUTINIB (PCI-32765), IN COMBINATION WITH CARFILZOMIB (KYPROLIS™) IN SUBJECTS WITH RELAPSED OR RELAPSED AND REFRACTORY MULTIPLE MYELOMA
Read the detailed description
Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoietic 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. PCI-32765 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 PCI-32765 in combination with carfilzomib (Kyprolis™) with and without dexamethasone in subjects with relapsed or relapsed and refractory multiple myeloma (MM).
- Conditions
- Multiple Myeloma
- Being tested
- Ibrutinib, Carfilzomib, Dexamethasone
- Keywords
- PCI-32765, Multiple Myeloma, Relapsed Refractory Multiple Myeloma, Bruton's Tyrosine Kinase, Carfilzomib, 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
CarfilzomibDrug
DexamethasoneDrug
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 - Dose Finding | Experimental | Ibrutinib PO 560mg + Carfilzomib IV 20/27mg/m2 + Dexamethasone PO 20mg Receives: Drug: Ibrutinib; Drug: Carfilzomib; Drug: Dexamethasone |
| Phase 2b - Main Study | Experimental | Ibrutinib PO 560mg + Carfilzomib IV 20/36mg/m2 + Dexamethasone PO 20mg Receives: Drug: Ibrutinib; Drug: Carfilzomib; Drug: Dexamethasone |
| Phase 2b - Sub-study | Experimental | Ibrutinib PO 840 mg + Carfilzomib IV 20/36 mg/m2 + Dexamethasone PO 20 mg Receives: Drug: Ibrutinib; Drug: Carfilzomib; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
-To evaluate the overall response (ORR) of ibrutinib in combination with carfilzomib and dexamethasone.
Measured: up to 4 years
Secondary outcomes (3)
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 progressive disease, death, or date of censoring for the subjects who had not progressed/died. The censoring date was the last adequate tumor assessment date.
Measured: Up to 4 years
Overall Survival
Time from date of first dose of study treatment to the date of death from any cause
Measured: Up to 4 years
Progression Free Survival (PFS)
Time from date of first dose of study treatment to the date of first documented evidence of progressive disease, death or date of censoring for the subjects not progressed/died. The censoring date was the last adequate tumor assessment date.
Measured: Up to 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2013 (estimated)
- Study startDec 2013
- Primary completionMar 2019
- Study completionMar 2019
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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharmacyclics LLC.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01962792
- Sponsor's protocol ID
- PCYC-1119-CA
- Other IDs
- Ibrutinib (PCI-32765)
- Status last verified
- Nov 2021
- First submitted
- 27 Sep 2013
- Last updated
- 21 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase 1/2b Study of the Bruton's Tyrosine Kinase Inhibitor, Ibrutinib (PCI-32765), in Combination With Carfilzomib (Kyprolis™) in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01962792
- Acronym / sponsor ID
- PCYC-1119-CA
- Conditions
- Multiple Myeloma
- Keywords
- PCI-32765, Multiple Myeloma, Relapsed Refractory Multiple Myeloma, Bruton's Tyrosine Kinase, Carfilzomib, Dexamethasone, Ibrutinib
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Pharmacyclics LLC.Industry (pharma, biotech, devices)
- Study start
- Dec 2013 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 14 Oct 2013 (estimated)
- Results
- Posted 21 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A MULTICENTER PHASE 1/2B STUDY OF THE BRUTON'S TYROSINE KINASE INHIBITOR, IBRUTINIB (PCI-32765), IN COMBINATION WITH CARFILZOMIB (KYPROLIS™) IN SUBJECTS WITH RELAPSED OR RELAPSED AND REFRACTORY MULTIPLE MYELOMA
Detailed description
Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoietic 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. PCI-32765 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 PCI-32765 in combination with carfilzomib (Kyprolis™) with and without dexamethasone in subjects with relapsed or relapsed and refractory multiple myeloma (MM).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase 1 - Dose Finding | Experimental | Drug: Ibrutinib, Drug: Carfilzomib, Drug: DexamethasoneIbrutinib PO 560mg + Carfilzomib IV 20/27mg/m2 + Dexamethasone PO 20mg |
| Phase 2b - Main Study | Experimental | Drug: Ibrutinib, Drug: Carfilzomib, Drug: DexamethasoneIbrutinib PO 560mg + Carfilzomib IV 20/36mg/m2 + Dexamethasone PO 20mg |
| Phase 2b - Sub-study | Experimental | Drug: Ibrutinib, Drug: Carfilzomib, Drug: DexamethasoneIbrutinib PO 840 mg + Carfilzomib IV 20/36 mg/m2 + Dexamethasone PO 20 mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Measurable disease of MM as defined by at least ONE of the following:
- Relapsed or relapsed and refractory MM after receiving at least 2 previous therapies, including an immunomodulator and bortezomib and had either no response or documented disease progression (according to IMWG criteria) to the most recent treatment regimen
- Adequate hematologic, hepatic, and renal function
- ECOG performance status of 0-2
- Must meet all inclusion criteria defined in main study and in addition the following criteria must be met:
Key exclusion criteria (6 listed)
- Subject must not have primary refractory disease
- Plasma cell leukemia, primary amyloidosis or POEMS syndrome
- Unable to swallow capsules or disease significantly affecting gastrointestinal function
- Requires anti-coagulation with warfarin or a vitamin K antagonist
- Requires treatment with strong CYP3A inhibitors
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 |
|---|---|---|
| Ibrutinib | Drug | Phase 1 - Dose Finding, Phase 2b - Main Study, Phase 2b - Sub-study |
| Carfilzomib | Drug | Phase 1 - Dose Finding, Phase 2b - Main Study, Phase 2b - Sub-study |
| Dexamethasone | Drug | Phase 1 - Dose Finding, Phase 2b - Main Study, Phase 2b - Sub-study |
Primary outcome
Overall Response Rate (ORR)
Time frame: up to 4 years
-To evaluate the overall response (ORR) of ibrutinib in combination with carfilzomib and dexamethasone.
3 secondary outcomes
Duration of Response (DOR)
Time frame: Up to 4 years
Overall Survival
Time frame: Up to 4 years
Progression Free Survival (PFS)
Time frame: Up to 4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ibrutinib, Carfilzomib and Dexamethasone in people with Multiple Myeloma, run by Pharmacyclics LLC. at 17 sites in 2 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 12 inclusion and 6 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 21 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Canada. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 21 Dec 2021). 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?
Overall Response Rate (ORR) (time frame: up to 4 years). 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 21 Dec 2021.