Study of the Safety and Pharmacokinetics of Carfilzomib in Subjects With Relapsed and Refractory Multiple Myeloma and Varying Degrees of Renal Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier:
NCT00721734
First received: July 22, 2008
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to assess the influence of renal impairment on carfilzomib in subjects with Multiple Myeloma (MM).


Condition Intervention Phase
Multiple Myeloma
Renal Insufficiency
Drug: Carfilzomib for Injection, PR-171
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 2 Study of the Safety and Pharmacokinetics of Carfilzomib in Subjects With Relapsed and Refractory Multiple Myeloma and Varying Degrees of Renal Function

Resource links provided by NLM:


Further study details as provided by Onyx Pharmaceuticals:

Primary Outcome Measures:
  • To assess the influence of renal impairment on the pharmacokinetics (PK) of carfilzomib in subjects with Multiple Myeloma (MM) [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: September 2008
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: carfilzomib Drug: Carfilzomib for Injection, PR-171
Carfilzomib, will be administered intravenously (IV) on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle.

  Eligibility

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

Inclusion Criteria:

  1. Written informed consent in accordance with federal, local, and institutional guidelines
  2. Males and females ≥ 18 years of age
  3. Multiple Myeloma
  4. Documented relapsed or progressive disease (PD) after receiving at least two prior treatment regimens (induction therapy with autologous stem cell transplant and maintenance is considered a single regimen), and must have achieved a minimal response or better to at least one of the regimens
  5. Current measurable disease, as indicated by one or more of the following:

    • Serum M-protein ≥ 0.5 g/dL
    • Urine M-protein ≥ 200 mg/24 hours
    • Serum Free Light Chain assay : Involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal
  6. Life expectancy of more than three months
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  8. Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN) and alanine aminotransferase (ALT) < 3 times ULN
  9. Total white blood cell (WBC) count ≥ 2,000/mm3
  10. Absolute neutrophil count (ANC) ≥ 1,000/mm3
  11. Hemoglobin ≥ 7 gm/dL

    • Subjects may receive red blood cell (RBC) transfusions or supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines
  12. Platelet count ≥ 30,000/ mm3
  13. Female subjects of child-bearing potential must have a negative serum pregnancy test within seven days of the first dose and agree to use dual methods of contraception during and for 3 months following last dose of drug. Post menopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from a pregnancy test
  14. Male subjects must use an effective barrier method of contraception during study and for three months following the last dose if sexually active with a female of child-bearing potential

Exclusion Criteria:

  1. Glucocorticoid therapy in a dose equivalent to prednisone ≥ 20 mg/day within 14 days prior to first dose of study drug
  2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  3. Plasma cell leukemia
  4. Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy dose as defined above, within 14 days prior to first dose of study drug or antibody therapy within 6 weeks prior to first dose of study drug
  5. Radiation therapy or immunotherapy within 3 weeks prior to first dose; localized radiation therapy within 1 week prior to first dose
  6. Participation in an investigational therapeutic study within 14 days prior to first dose of study drug
  7. Prior carfilzomib treatment
  8. Pregnant or lactating females
  9. Major surgery within 3 weeks prior to first dose of study drug
  10. Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities or myocardial infarction in the three months prior to first dose of study drug
  11. Uncontrolled hypertension
  12. Recent history of acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose of study drug
  13. Known or suspected HIV infection, known HIV seropositivity
  14. Active hepatitis A, B, or C infection
  15. Other malignancy within the past 3 years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer < Gleason Grade 7 with stable prostate specific antigen (PSA) levels
  16. Any clinically significant medical or psychiatric disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
  17. Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose and/or within 14 days prior to enrollment
  18. Subjects in whom the required program of oral hydration and intravenous fluid hydration is contraindicated, e.g., due to preexisting pulmonary or cardiac impairment
  19. Subjects with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis
  20. Subjects with a known contraindication to receiving dexamethasone or allopurinol
  21. Receipt of granulocyte- and granulocyte/ macrophage- colony stimulating factor (G-CSF and GM-CSF) within 1 week prior to first dose of study drug
  22. Receipt of pegylated G-CSF within 2 weeks prior to first dose of study drug
  23. RBC and platelet transfusions within 7 days prior to first dose of study drug
  24. Subjects with known or suspected cardiac amyloidosis
  25. Subjects with myelodysplastic syndrome
  26. Subjects undergoing peritoneal dialysis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00721734

Locations
United States, California
University of California- San Francisco
San Francisco, California, United States, 94143
United States, Maryland
University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Cornell University
New York, New York, United States, 10021
Sponsors and Collaborators
Onyx Therapeutics, Inc.
Investigators
Study Director: Alvin Wong, PharmD Onyx Therapeutics, Inc.
  More Information

No publications provided

Responsible Party: Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier: NCT00721734     History of Changes
Other Study ID Numbers: PX-171-005
Study First Received: July 22, 2008
Last Updated: November 12, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Onyx Pharmaceuticals:
Myeloma
Renal Insufficiency
Proteasome
Hematological
carfilzomib
PR-171

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Renal Insufficiency
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
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on April 16, 2014