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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: pomalidomide

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-8582
    • Kyusyu University Hospital
  • Kamogawa, Japan, 296-1602
    • Kameda General Hospital
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Okayama, Japan, 701-1192
    • Okayama Medical Center
  • Aichi
    • Nagoya, Aichi, Japan, 467-8602
      • Nagoya City University Hospital
  • Kanagawa
    • Isehara, Kanagawa, Japan, 259-1193
      • Tokai University Hospital
  • Saitama
    • Kawagoe, Saitama, Japan, 350-8550
      • Saitama Medical Center, Saitama Medical University
  • Tokyo
    • Tyuuou, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pomalidomide; 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; 2 mg or 4mg oral pomalidomide once per day on Days 1-21 of a 28-day cycle

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Toru Sasaki, Celgene K.K

Publications and helpful links

General Publications

• Matsue K, Iwasaki H, Chou T, Tobinai K, Sunami K, Ogawa Y, Kurihara M, Midorikawa S, Zaki M, Doerr T, Iida S. Pomalidomide alone or in combination with dexamethasone in Japanese patients with refractory or relapsed and refractory multiple myeloma. Cancer Sci. 2015 Nov;106(11):1561-7. doi: 10.1111/cas.12772. Epub 2015 Nov 4.
• Mark TM, Forsberg PA, Rossi AC, Pearse RN, Pekle KA, Perry A, Boyer A, Tegnestam L, Jayabalan D, Coleman M, Niesvizky R. Phase 2 study of clarithromycin, pomalidomide, and dexamethasone in relapsed or refractory multiple myeloma. Blood Adv. 2019 Feb 26;3(4):603-611. doi: 10.1182/bloodadvances.2018028027.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2012
• Primary Completion (Actual): July 8, 2015
• Study Completion (Actual): July 8, 2015

Study Registration Dates

• First Submitted: March 29, 2012
• First Submitted That Met QC Criteria: March 30, 2012
• First Posted (Estimate): April 2, 2012

Study Record Updates

• Last Update Posted (Actual): November 12, 2019
• Last Update Submitted That Met QC Criteria: November 7, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Pomalidomide
• Other Study ID Numbers: CC-4047-MM-004