A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Subjects With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study (NIMBUS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Celgene Corporation
ClinicalTrials.gov Identifier:
NCT01311687
First received: March 8, 2011
Last updated: November 5, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to compare efficacy and safety of pomalidomide in combination with low-dose dexamethasone versus high-dose dexamethasone in subjects with refractory or relapsed and refractory multiple myeloma.


Condition Intervention Phase
Multiple Myeloma
Drug: pomalidomide
Drug: dexamethasone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone Versus High-Dose Dexamethasone in Subjects With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study

Resource links provided by NLM:


Further study details as provided by Celgene Corporation:

Primary Outcome Measures:
  • Time to disease progression or death [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Number of months between randomization and disease progression based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study


Secondary Outcome Measures:
  • Adverse events [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Number of participants with adverse events

  • Number of patients alive or dead [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
    Number of patients alive or dead

  • Number of patients with response according to International Myeloma Working Group (IMWG) Uniform response criteria [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Number of patients with response according to the Independent Response Adjudication Committee (IRAC) based on the IMWG criteria

  • Number of patients with response according to European Group for Blood and Marrow Transplantation (EBMT) criteria [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Number of patients with response according to the Independent Response Adjudication Committee (IRAC) based on the EBMT criteria

  • Time to progression [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Time from randomization to the first documented progression confirmed by the Independent Response Adjudication Committee (IRAC)

  • Time to IMWG or EBMT response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Time from randomization to the initial documented response based on IMWG or EBMT criteria

  • Time from response to disease progression [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Time from the initial documented response to confirmed disease progression

  • Time to increased hemoglobin value [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Time to increased hemoglobin value

  • Time to improvement of bone pain [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Time to improvement of bone pain

  • Time to improvement of renal function [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Time to improvement of renal function

  • Time to improvement of Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Time to improvement of ECOG performance status

  • Change from baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients with Multiple Myeloma (EORTC QLQ-MY20) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Change from baseline in the EORTC QLQ-MY20 Module

  • Change from baseline in the European Organization for Research and Treatment of Cancer Cancer Quality of Life Questionnaire for Patients with Cancer (EORTC QLQ-C30) Module [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Change from baseline in the EORTC QLQ-C30 Module

  • Change from baseline in the European Quality of Life-5 Dimensions (EQ-5D) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Change from baseline in the descriptive system of the EQ-5D


Estimated Enrollment: 426
Study Start Date: March 2011
Estimated Study Completion Date: December 2014
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral Pomalidomide plus Low-Dose Dexamethasone

For Subjects ≤ 75 years of age:

4 mg pomalidomide will be administered by mouth on Days 1-21 of each 28-day treatment cycle until disease progression and 40 mg low-dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression

For Subjects > 75 years of age:

4 mg pomalidomide will be administered by mouth on Days 1-21 of each 28-day treatment cycle until disease progression and 20 mg low dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression

Drug: pomalidomide
4 mg pomalidomide will be administered by mouth on Days 1-21 of each 28-day treatment cycle until disease progression
Other Name: CC-4047
Drug: dexamethasone

For Subjects ≤ 75 years of age:

40 mg of low-dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression

For Subjects > 75 years of age:

20 mg low-dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression

Active Comparator: High-Dose Dexamethasone

For Subjects ≤ 75 years of age:

40 mg high-dose dexamethasone will be administered by mouth once per day on Days 1 through 4, 9 through 12, and 17 through 20 of a 28-day cycle until disease progression

For Subjects > 75 years of age:

20 mg high-dose dexamethasone will be administered by mouth once per day on Days 1 through 4, 9 through 7, and 17 through 20 of a 28-day cycle until disease progression

Drug: dexamethasone

For Subjects ≤ 75 years of age:

40 mg of low-dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression

For Subjects > 75 years of age:

20 mg low-dose dexamethasone will be administered by mouth once per day on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be ≥ 18 years of age
  • Subjects must have documented diagnosis of multiple myeloma and have measurable disease
  • Subjects must have undergone prior treatment with ≥ 2 treatment lines of anti-myeloma therapy
  • Subjects must have either refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy
  • All subjects must have received at least 2 consecutive cycles of prior treatment that included lenalidomide and bortezomib
  • All subjects must have failed treatment with both lenalidomide and bortezomib in one of the following ways: 1) Documented progressive disease on or within 60 days of completing treatment with lenalidomide and/or bortezomib, or 2) In case of prior response [≥ partial response (PR)] to lenalidomide or bortezomib, subjects must have relapsed within 6 months after stopping treatment with lenalidomide and/or bortezomib-containing regimens, or 3) Subjects who have not had a ≥ minimal response (MR) and have developed intolerance/toxicity after a minimum of two cycles of lenalidomide- and/or bortezomib-containing regimen
  • Patients must have received adequate prior alkylator therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
  • Females of childbearing potential (FCBP) must not become pregnant for 28 days prior to initiation of study drug, during the study, and for 28 days after discontinuation
  • Females must agree to abstain from breastfeeding during study participation and 28 days after study drug discontinuation
  • Males must agree to use a latex condom during any sexual during the study and for 28 days following discontinuation from this study
  • Males must also agree to refrain from donating semen or sperm while on pomalidomide and for 28 days after discontinuation from this study

Exclusion Criteria:

  • Any of the following laboratory abnormalities:

    • Absolute neutrophil count (ANC) < 1,000/μL
    • Platelet count < 75,000/ μL for subjects in whom < 50% of bone marrow nucleated cells are plasma cells
    • Creatinine Clearance < 45 mL/min
    • Corrected serum calcium > 14 mg/dL
    • Hemoglobin ≤ 8 g/dL
    • Serum glutamic oxaloacetic transaminase (SGOT)/ aspartate aminotransferase (AST) or Transaminase, serum glutamic pyruvic (SGPT)/ alanine aminotransferase (ALT) > 3.0 x upper limit of normal (ULN)
    • Serum total bilirubin > 2.0 mg/dL
  • Previous therapy with Pomalidomide
  • Hypersensitivity to thalidomide, lenalidomide, or dexamethasone
  • Resistance to high-dose dexamethasone used in the last line of therapy
  • Peripheral neuropathy ≥ Grade 2
  • Subjects who received an allogeneic bone marrow or allogeneic peripheral blood stem cell transplant
  • Subjects who are planning for or who are eligible for stem cell transplant
  • Subjects with any one of the following: 1) Congestive heart failure, 2) Myocardial infarction within 12 months prior to starting study treatment, 3) Unstable or poorly controlled angina pectoris, including Prinzmetal variant angina pectoris
  • Subjects who received any of the following within the last 14 days of initiation of study treatment: 1) Plasmapheresis, 2) Major surgery, 3) Radiation therapy, 4) Use of any anti-myeloma drug therapy
  • Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of treatment
  • Subjects with conditions requiring chronic steroid or immunosuppressive treatment
  • Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
  • Incidence of gastrointestinal disease that may significantly alter the absorption of pomalidomide
  • Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subjects from signing the informed consent form
  • Pregnant or breastfeeding females
  • Known Human Immunodeficiency Virus (HIV) positivity or active infectious hepatitis A, B or C
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01311687

  Show 93 Study Locations
Sponsors and Collaborators
Celgene Corporation
Investigators
Study Director: Mohamed Zaki, MD, PhD Celgene Corporation
  More Information

No publications provided

Responsible Party: Celgene Corporation
ClinicalTrials.gov Identifier: NCT01311687     History of Changes
Other Study ID Numbers: CC-4047-MM-003, 2010-019820-30
Study First Received: March 8, 2011
Last Updated: November 5, 2013
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Greece: National Organization of Medicines
Italy: The Italian Medicines Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Russia: Ministry of Health of the Russian Federation
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Celgene Corporation:
Myeloma
Multiple Myeloma
Relapsed Multiple Myeloma
Relapsed and Refractory Multiple Myeloma
Refractory Myeloma
Resistant Multiple Myeloma
Treatment-resistant Multiple Myeloma
Pomalidomide
Lenalidomide-resistant
Bortezomib-resistant

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones

ClinicalTrials.gov processed this record on April 16, 2014