Phase 2
Completed N=92
Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
Source: ClinicalTrials.gov NCT01478581 ↗Enrolled (actual)
92
Serious AEs
33.7%
Results posted
Jun 2018
Primary outcomePrimary: The Clinical Benefit Response (CBR) — 1; 1; 0; 12 Participants
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)
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The Clinical Benefit Response (CBR) |
1; 1; 0; 12 | — |
| SECONDARY To Evaluate the Efficacy of PCI-32765 by Assessing ORR |
0; 1; 0; 2 | — |
| SECONDARY Pharmacokinetics (PK). (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Maximum Observed Plasma Concentration (Cmax) |
157; 103; 219; 166 | — |
| SECONDARY Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Time to Maximum Observed Plasma Concentration (Tmax). |
2.73; 2.32; 1.95; 2.25 | — |
| SECONDARY 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). |
1094; 723; 1423; 1230 | — |
| SECONDARY Pharmacokinetics (PK) (Assessed by Sampling and Testing for Drug and Metabolite Levels at Designated Time Points). Mean Terminal Elimination Half-life (t1/2,Term). |
7.76; 6.95; 8.42; 6.90 | — |
| SECONDARY 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) |
2.75; 1.90; 1.88; 1.31 | — |
| SECONDARY 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) |
0.952; 1.47; 1.39; 1.39 | — |
| SECONDARY 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) |
1.44; 2.21; 1.90; 1.96 | — |
| SECONDARY Duration of Clinical Benefit Response (DCB) |
27.6; 3.7; 11.5 | — |
| SECONDARY Duration of Response (DOR) |
3.7; 15.4 | — |
Eligibility Criteria
Inclusion Criteria
- 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.
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 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.
Data sourced from ClinicalTrials.gov (NCT01478581). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.