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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01568294
First received: March 29, 2012
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: pomalidomide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events [ Time Frame: Up to 28 Days ] [ Designated as safety issue: Yes ]
    Incidence of dose-limiting toxicity in accordance with Common Terminology Criteria for Adverse Events


Secondary Outcome Measures:
  • Maximum observed plasma concentration (Cmax) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration (Cmax)

  • Time to maximum observed plasma concentration (tmax) [ Time Frame: Up 28 days ] [ Designated as safety issue: No ]
    Time to maximum observed plasma concentration (tmax)

  • Area under the plasma concentration-time curve (AUC0-t) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve (AUC0-t)

  • Apparent total plasma clearance (CL/F) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Apparent total plasma clearance (CL/F)

  • Apparent total volume of distribution (Vz/F) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Apparent total volume of distribution (Vz/F)

  • Estimate of the terminal elimination half-life in plasma (t1/2) [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Estimate of the terminal elimination half-life in plasma (t1/2)

  • Safety (the number of participants with adverse events, incidence, severity, causality) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Safety (the number of participants with adverse events, incidence, severity, causality)

  • Progression-free survival [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Progression-free survival

  • Myeloma response [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Myeloma response

  • Time to Response [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Time to Response

  • Duration of Response [ Time Frame: Up to 28 days ] [ Designated as safety issue: No ]
    Duration of Response


Enrollment: 12
Study Start Date: April 2012
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01568294

Locations
Japan
Nagoya City University Hospital
Nagoya, Aichi, Japan, 467-8602
Tokai University Hospital
Isehara, Kanagawa, Japan, 259-1193
Saitama Medical Center, Saitama Medical University
Kawagoe, Saitama, Japan, 350-8550
National Cancer Center Hospital
Tyuuou, Tokyo, Japan, 104-0045
Kyusyu University Hospital
Fukuoka, Japan, 812-8582
Kameda General Hospital
Kamogawa, Japan, 296-1602
Niigata Cancer Center Hospital
Niigata, Japan, 951-8566
Okayama Medical Center
Okayama, Japan, 701-1192
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Toru Sasaki Celgene K.K
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01568294     History of Changes
Other Study ID Numbers: CC-4047-MM-004
Study First Received: March 29, 2012
Last Updated: December 13, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Pomalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014