Japanese Phase 1 Study to Evaluate Tolerated Dose, Safety, and Efficacy of Pomalidomide in Patients With Refractory or Relapsed and Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to determine the tolerated dose of pomalidomide and also to evaluate the pharmacokinetics, safety and efficacy of pomalidomide in patients with refractory or relapsed and refractory multiple myeloma.

Official Title
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A Phase 1, Multicenter, Open-label, Dose-escalation Study in Japan to Determine the Tolerated Dose and to Evaluate the Safety, Efficacy, and Pharmacokinetics of Pomalidomide Alone or in Combination With Dexamethasone in Patients With Refractory or Relapsed and Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: pomalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be ≥ 20 years of age at the time of signing the informed consent document The subject must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures are conducted. Must be able to adhere to the study visit schedule and other protocol requirements Subjects must have documented diagnosis of multiple myeloma and have measurable disease All subjects must have had at least 2 prior lines of anti-myeloma therapy. Induction therapy followed by stem cell transplant and consolidation/maintenance will be considered as one line All subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last anti-myeloma therapy. Primary refractory: Subjects who have never achieved any response better than progressive disease (PD) to any previous line of anti-myeloma therapy. Relapsed and refractory: Subjects who have relapsed after having achieved at least stable disease (SD) to at least one prior regimen and then developed progressive disease (PD) on or within 60 days of completing their last anti-myeloma therapy. Subjects must have also undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of bortezomib (either in separate regimens or within the same regimen). All subjects must have received adequate prior alkylator therapy. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2. Exclusion Criteria: Pregnant or breastfeeding females Hypersensitivity to thalidomide, lenalidomide, or dexamethasone ≥ Grade 3 rash during prior thalidomide or lenalidomide therapy Patients unable or unwilling to undergo antithrombotic prophylactic treatment will not be eligible to participate in this study Any of the following laboratory abnormalities: Absolute neutrophil count (ANC) < 1,000/µL Platelet count < 75,000/µL for patients in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count < 30,000/µL for patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells Creatinine Clearance < 45 mL/min according to Cockcroft-Gault formula Corrected serum calcium > 14 mg/dL (> 3.5 mmol/L) Hemoglobin < 8 g/dL (< 4.9 mmol/L; prior RBC transfusion or recombinant human erythropoietin use is permitted) Serum glutamic oxaloacetic transaminase (SGOT) /aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT) /alanine aminotransferase (ALT) > 3.0 x upper limit of normal (ULN) Serum total bilirubin > 2.0 mg/dL (34.2 μmol/L); or ≥ 3.0 x upper limit of normal (ULN) for subjects with hereditary benign hyperbilirubinaemia Peripheral neuropathy ≥ Grade 2 Patients who received any of the following within the last 14 days of initiation of study treatment: Plasmapheresis Major surgery (kyphoplasty is not considered major surgery) Radiation therapy Use of any anti-myeloma drug therapy

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pomalidomide<br>Patients will receive pomalidomide orally on Days 1-21 of each 28-day cycle until when/if a discontinuation criterion, e.g., disease progression, development of an unacceptable toxicity, voluntary withdrawal, or pomalidomide is in market for the target indication. | Drug: pomalidomide<br>* 2 mg or 4mg oral pomalidomide once per day on Days 1-21 of a 28-day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events | Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events | Up to 28 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) | Maximum observed plasma concentration (Cmax) | Up to 28 days | 
| Time to maximum observed plasma concentration (tmax) | Time to maximum observed plasma concentration (tmax) | Up 28 days | 
| Area under the plasma concentration-time curve (AUC0-t) | Area under the plasma concentration-time curve (AUC0-t) | Up to 28 days | 
| Apparent total plasma clearance (CL/F) | Apparent total plasma clearance (CL/F) | Up to 28 days | 
| Apparent total volume of distribution (Vz/F) | Apparent total volume of distribution (Vz/F) | Up to 28 days | 
| Estimate of the terminal elimination half-life in plasma (t1/2) | Estimate of the terminal elimination half-life in plasma (t1/2) | Up to 28 days | 
| Safety (the number of participants with adverse events, incidence, severity, causality) | Safety (the number of participants with adverse events, incidence, severity, causality) | Up to 2 years | 
| Progression-free survival | Progression-free survival | Up to 28 days | 
| Myeloma response | Myeloma response | Up to 28 days | 
| Time to Response | Time to Response | Up to 28 days | 
| Duration of Response | Duration of Response | Up to 28 days |