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

Phase 1
Completed
Conditions
Multiple Myeloma
Interventions
Registration Number
NCT01568294
Lead Sponsor
Celgene
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
pomalidomidepomalidomidePatients 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.
Primary Outcome Measures
NameTimeMethod
Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse EventsUp to 28 Days

Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events

Secondary Outcome Measures
NameTimeMethod
Estimate of the terminal elimination half-life in plasma (t1/2)Up to 28 days

Estimate of the terminal elimination half-life in plasma (t1/2)

Area under the plasma concentration-time curve (AUC0-t)Up to 28 days

Area under the plasma concentration-time curve (AUC0-t)

Myeloma responseUp to 28 days

Myeloma response

Maximum observed plasma concentration (Cmax)Up to 28 days

Maximum observed plasma concentration (Cmax)

Apparent total plasma clearance (CL/F)Up to 28 days

Apparent total plasma clearance (CL/F)

Apparent total volume of distribution (Vz/F)Up to 28 days

Apparent total volume of distribution (Vz/F)

Safety (the number of participants with adverse events, incidence, severity, causality)Up to 2 years

Safety (the number of participants with adverse events, incidence, severity, causality)

Progression-free survivalUp to 28 days

Progression-free survival

Time to maximum observed plasma concentration (tmax)Up 28 days

Time to maximum observed plasma concentration (tmax)

Duration of ResponseUp to 28 days

Duration of Response

Time to ResponseUp to 28 days

Time to Response

Trial Locations

Locations (8)

Nagoya City University Hospital

🇯🇵

Nagoya, Aichi, Japan

National Cancer Center Hospital

🇯🇵

Tyuuou, Tokyo, Japan

Niigata Cancer Center Hospital

🇯🇵

Niigata, Japan

Kameda General Hospital

🇯🇵

Kamogawa, Japan

Okayama Medical Center

🇯🇵

Okayama, Japan

Tokai University Hospital

🇯🇵

Isehara, Kanagawa, Japan

Saitama Medical Center, Saitama Medical University

🇯🇵

Kawagoe, Saitama, Japan

Kyusyu University Hospital

🇯🇵

Fukuoka, Japan

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