Multiple MyelomaPhase 2NCT01478581
Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
A Phase 2 study testing PCI-32765 and Dexamethasone in people with Multiple Myeloma, run by Pharmacyclics LLC. at 11 sites in United States.
Trial summary
The primary objective of this study is to determine the efficacy of PCI-32765, both as a single agent and in combination with dexamethasone, in subjects with relapsed or relapsed and refractory Multiple Myeloma (MM) 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?
- PCI-32765 and Dexamethasone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 11 sitesUnited States
- Study dates
- Mar 2012to Aug 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
- Diagnosis of symptomatic MM with measurable disease, defined here as having at least one of the following:
- Serum monoclonal protein (M-protein) ≥0.5 g/dL as determined by serum protein electrophoresis (SPEP)
- Urine M-protein ≥200 mg/24 hrs
- Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal
- Relapsed or relapsed and refractory MM after receiving at least 2 but no more than 5 previous lines of therapy, 1 of which must be an immunomodulator.
- Refractory myeloma (to most recent treatment) is defined as disease that is nonresponsive while on treatment or progressive disease within 60 days after the completion of preceding treatment. Nonresponsive disease is defined as either failure to achieve minimal response or development of progressive disease while on therapy.
- Men and women ≥18 years of age.
- ECOG performance status of ≤ 1.
Who cannot join
- Subject must not have primary refractory disease defined as disease that is nonresponsive in subjects who have never achieved a minor response (MR) or better with any therapy.
- Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome, osteosclerotic myeloma, or Crow-Fukase syndrome.
- Plasma cell leukemia.
- Primary amyloidosis.
- Certain exclusions on prior therapy.
- ANC <0.75 x 10^9/L independent of growth factor support.
Show all 12Show fewer
- Platelets <50 x 10^9/L) independent of transfusion support.
- AST or ALT ≥3.0 x upper limit of normal (ULN).
- Total bilirubin >2.5 x ULN, unless due to Gilbert's syndrome.
- Creatinine >2.5 mg/dL.
- Unable to swallow capsules or disease significantly affecting gastrointestinal function.
- Requires anti-coagulation with warfarin or a vitamin K antagonist. Requires treatment with strong CYP3A4/5 inhibitors.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
SITE-8
Ann Arbor, Michigan, 48109
SITE-5
Baltimore, Maryland, 21287
SITE-4
Boston, Massachusetts, 02215
SITE-11
Dallas, Texas, 75390
SITE-6
Hackensack, New Jersey, 07601
SITE-13
La Jolla, California, 92093
SITE-1
Nashville, Tennessee, 37203
SITE-10
New York, New York, 10029
SITE-3
New York, New York, 10065
SITE-9
Seattle, Washington, 98109
SITE-2
St Louis, Missouri, 63110
About this study
Official title: A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
The primary objective of this study is to determine the efficacy of PCI-32765, both as a single agent and in combination with dexamethasone, in subjects with relapsed or relapsed and refractory Multiple Myeloma (MM)
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 clinical trials. The current study is designed and intended to determine the effects of PCI-32765 in subjects with MM.
- Conditions
- Multiple Myeloma
- Being tested
- PCI-32765, Dexamethasone
- Keywords
- PCI-32765, Multiple Myeloma, Relapsed Refractory Multiple Myeloma, Bruton's Tyrosine Kinase
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCI-32765Drug
Also called Ibrutinib
DexamethasoneDrug
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | PCI-32765 420 mg per day Receives: Drug: PCI-32765 |
| Cohort 2 | Experimental | PCI-32765 560 mg per day, 40 mg dexamethasone (oral) once per week Receives: Drug: PCI-32765; Drug: Dexamethasone |
| Cohort 3 | Experimental | PCI-32765 840 mg per day Receives: Drug: PCI-32765 |
| Cohort 4 | Experimental | PCI-32765 840 mg per day, 40 mg dexamethasone (oral) once per week Receives: Drug: PCI-32765; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Clinical Benefit Response (CBR)
The clinical benefit response (CBR) rate, defined as the proportion of subjects who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or minimal response (MR) as assessed by the modified International Myeloma Working Group (IMWG) response criteria
Measured: From the date of first study treatment until disease progression per IMWG, up to 60 months
Secondary outcomes (10)
To Evaluate the Efficacy of PCI-32765 by Assessing ORR
The objective response rate, defined as the proportion of subjects who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), as assessed by the modified International Myeloma Working Group (IMWG) response criteria.
Measured: From the date of first study treatment until disease progression per IMWG, up to 60 months
Pharmacokinetics (PK). (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Maximum Observed Plasma Concentration (Cmax)
Ibrutinib and PCI-45227 concentrations were measurable following once-daily dosing of ibrutinib in subjects with MM. The following time-points were included: 0hr, 1hr, 2hr, 7hr, 24hr post-dose. Maximum observed plasma concentration of ibrutinib during the dosing interval on Day 8.
Measured: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Time to Maximum Observed Plasma Concentration (Tmax).
Ibrutinib and PCI-45227 concentrations were measurable following once-daily dosing of ibrutinib in subjects with MM. The following time-points were included: 0hr, 1hr, 2hr, 7hr, 24hr post-dose. Time to corresponding maximum observed plasma concentration of ibrutinib during the dosing interval on Day 8.
Measured: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h).
Ibrutinib and PCI-45227 concentrations were measurable following once-daily dosing of ibrutinib in subjects with MM. The following time-points were included: 0hr, 1hr, 2hr, 7hr, 24hr post-dose. Ibrutinib AUC0-24h calculated using linear trapezoidal summation after dosing from time 0 to 24 hours on Day 8.
Measured: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Terminal Elimination Half-life (t1/2,Term).
Ibrutinib and PCI-45227 concentrations were measurable following once-daily dosing of ibrutinib in subjects with MM. The following time-points were included: 0hr, 1hr, 2hr, 7hr, 24hr post-dose. Ibrutinib terminal elimination half-life associated with the terminal slope (λz) of the semi-logarithmic plasma concentration-time curve, calculated as 0.693/λz on Day 8.
Measured: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Accumulation Ratio for AUC0-24h (Acc. Ratio AUC0-24h)
Ibrutinib and PCI-45227 concentrations were measurable following once-daily dosing of ibrutinib in subjects with MM. The following time-points were included: 0hr, 1hr, 2hr, 7hr, 24hr post-dose. Acc. Ratio calculated as Day 8 ibrutinib AUC0-24h/ Day 1 ibrutinib AUC0-24h.
Measured: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Metabolite-to-Parent Ratio for Cmax (M/P Cmax)
Ibrutinib and PCI-45227 concentrations were measurable following once-daily dosing of ibrutinib in subjects with MM. The following time-points were included: 0hr, 1hr, 2hr, 7hr, 24hr post-dose. Calculated as (PCI-45227 Cmax/PCI-45227 molecular weight)/(ibrutinib Cmax/ibrutinib molecular weight) on Day 8.
Measured: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Metabolite-to-Parent Ratio for AUC0-24h (M/P AUC0-24h)
Ibrutinib and PCI-45227 concentrations were measurable following once-daily dosing of ibrutinib in subjects with MM. The following time-points were included: 0hr, 1hr, 2hr, 7hr, 24hr post-dose. Calculated as (PCI-45227 AUC0-24h/PCI-45227 molecular weight)/(ibrutinib AUC0-24h/ibrutinib molecular weight) on Day 8.
Measured: Procedure was performed up to 60 weeks.
Duration of Clinical Benefit Response (DCB)
DCB is defined as the time from first observation of response to the time of disease progression.
Measured: From the date of first study treatment until disease progression per IMWG, up to 60 months
Duration of Response (DOR)
The time interval between the date of initial documentation of a response and the date of first documented evidence of progressive disease, death, or date of censoring for the subjects not progressed/died. The censoring date is the last adequate tumor assessment date.
Measured: up to 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2011 (estimated)
- Study startMar 2012
- Primary completionAug 2018
- Study completionAug 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 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
- NCT01478581
- Sponsor's protocol ID
- PCYC-1111-CA
- Other IDs
- PCI-32765
- Status last verified
- Oct 2019
- First submitted
- 18 Nov 2011
- Last updated
- 10 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT01478581
- Acronym / sponsor ID
- PCYC-1111-CA
- Conditions
- Multiple Myeloma
- Keywords
- PCI-32765, Multiple Myeloma, Relapsed Refractory Multiple Myeloma, Bruton's Tyrosine Kinase
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- Pharmacyclics LLC.Industry (pharma, biotech, devices)
- Study start
- Mar 2012 (actual)
- Primary completion
- Aug 2018 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 23 Nov 2011 (estimated)
- Results
- Posted 26 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to determine the efficacy of PCI-32765, both as a single agent and in combination with dexamethasone, in subjects with relapsed or relapsed and refractory Multiple Myeloma (MM)
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 clinical trials. The current study is designed and intended to determine the effects of PCI-32765 in subjects with MM.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: PCI-32765PCI-32765 420 mg per day |
| Cohort 2 | Experimental | Drug: PCI-32765, Drug: DexamethasonePCI-32765 560 mg per day, 40 mg dexamethasone (oral) once per week |
| Cohort 3 | Experimental | Drug: PCI-32765PCI-32765 840 mg per day |
| Cohort 4 | Experimental | Drug: PCI-32765, Drug: DexamethasonePCI-32765 840 mg per day, 40 mg dexamethasone (oral) once per week |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of symptomatic MM with measurable disease, defined here as having at least one of the following:
- Relapsed or relapsed and refractory MM after receiving at least 2 but no more than 5 previous lines of therapy, 1 of which must be an immunomodulator.
- Refractory myeloma (to most recent treatment) is defined as disease that is nonresponsive while on treatment or progressive disease within 60 days after the completion of preceding treatment. Nonresponsive disease is defined as either failure to achieve minimal response or development of progressive disease while on therapy.
- Men and women ≥18 years of age.
- ECOG performance status of ≤ 1.
Key exclusion criteria (12 listed)
- Subject must not have primary refractory disease defined as disease that is nonresponsive in subjects who have never achieved a minor response (MR) or better with any therapy.
- Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome, osteosclerotic myeloma, or Crow-Fukase syndrome.
- Plasma cell leukemia.
- Primary amyloidosis.
- Certain exclusions on prior therapy.
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 |
|---|---|---|
| PCI-32765Also: Ibrutinib | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| Dexamethasone | Drug | Cohort 2, Cohort 4 |
Primary outcome
The Clinical Benefit Response (CBR)
Time frame: From the date of first study treatment until disease progression per IMWG, up to 60 months
The clinical benefit response (CBR) rate, defined as the proportion of subjects who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or minimal response (MR) as assessed by the modified International Myeloma Working Group (IMWG) response criteria
10 secondary outcomes
To Evaluate the Efficacy of PCI-32765 by Assessing ORR
Time frame: From the date of first study treatment until disease progression per IMWG, up to 60 months
Pharmacokinetics (PK). (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Maximum Observed Plasma Concentration (Cmax)
Time frame: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Time to Maximum Observed Plasma Concentration (Tmax).
Time frame: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h).
Time frame: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Terminal Elimination Half-life (t1/2,Term).
Time frame: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Accumulation Ratio for AUC0-24h (Acc. Ratio AUC0-24h)
Time frame: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Metabolite-to-Parent Ratio for Cmax (M/P Cmax)
Time frame: Procedure was performed up to 60 weeks.
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Metabolite-to-Parent Ratio for AUC0-24h (M/P AUC0-24h)
Time frame: Procedure was performed up to 60 weeks.
Duration of Clinical Benefit Response (DCB)
Time frame: From the date of first study treatment until disease progression per IMWG, up to 60 months
Duration of Response (DOR)
Time frame: up to 3 Years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2020.
- 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.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PCI-32765 and Dexamethasone in people with Multiple Myeloma, run by Pharmacyclics LLC. at 11 sites in United States.
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 8 inclusion and 12 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 10 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 11 sites in United States. 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 26 Jun 2018). 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?
The Clinical Benefit Response (CBR) (time frame: From the date of first study treatment until disease progression per IMWG, up to 60 months). 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 10 Mar 2020.