TriangleNCT01478581 · REGISTRY CONDITION SEARCH
Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2020-03-10
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)
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
The Clinical Benefit Response (CBR)
To Evaluate the Efficacy of PCI-32765 by Assessing ORR
Pharmacokinetics (PK). (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Maximum Observed Plasma Concentration (Cmax)
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Time to Maximum Observed Plasma Concentration (Tmax).
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).
Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Terminal Elimination Half-life (t1/2,Term).
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)
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)
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)
Duration of Clinical Benefit Response (DCB)
Duration of Response (DOR)
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Diagnosis of symptomatic MM with measurable disease, defined here as having at least one of the following: 1. Serum monoclonal protein (M-protein) ≥0.5 g/dL as determined by serum protein electrophoresis (SPEP) 2. Urine M-protein ≥200 mg/24 hrs 3. 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. Exclusion Criteria: * 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. * 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- PCI-32765 420 mg per day
- intervention Names
- Drug: PCI-32765
- label
- Cohort 1
- type
- EXPERIMENTAL
- description
- PCI-32765 560 mg per day, 40 mg dexamethasone (oral) once per week
- intervention Names
- Drug: PCI-32765
- Drug: Dexamethasone
- label
- Cohort 2
- type
- EXPERIMENTAL
- description
- PCI-32765 840 mg per day
- intervention Names
- Drug: PCI-32765
- label
- Cohort 3
- type
- EXPERIMENTAL
- description
- PCI-32765 840 mg per day, 40 mg dexamethasone (oral) once per week
- intervention Names
- Drug: PCI-32765
- Drug: Dexamethasone
- label
- Cohort 4
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Cohort 1
- Cohort 2
- Cohort 3
- Cohort 4
- name
- PCI-32765
- other Names
- Ibrutinib
- type
- DRUG
- arm Group Labels
- Cohort 2
- Cohort 4
- name
- Dexamethasone
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 92
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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
- measure
- The Clinical Benefit Response (CBR)
- time Frame
- From the date of first study treatment until disease progression per IMWG, up to 60 months
- secondary Outcomes
- description
- 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.
- measure
- 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
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- 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.
- measure
- 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.
- description
- DCB is defined as the time from first observation of response to the time of disease progression.
- measure
- Duration of Clinical Benefit Response (DCB)
- time Frame
- From the date of first study treatment until disease progression per IMWG, up to 60 months
- description
- 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.
- measure
- Duration of Response (DOR)
- time Frame
- up to 3 Years
Full study description
- brief 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)
- 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.
Source references
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice