Safety Study of the Proteasome Inhibitor PR-171 (Carfilzomib for Injection) in Patients With Hematological Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00150462
First received: September 6, 2005
Last updated: January 3, 2014
Last verified: January 2014

September 6, 2005
January 3, 2014
September 2005
October 2009   (final data collection date for primary outcome measure)
To evaluate the safety and tolerability of carfilzomib (PR-171), including determination of its Dose Limiting Toxicity (DTL) and Maximum Tolerated Dose (MTD). [ Time Frame: Up to 12 months. ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00150462 on ClinicalTrials.gov Archive Site
To determine the pharmacodynamics (PDn) of carfilzomib. [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
Not Provided
 
Safety Study of the Proteasome Inhibitor PR-171 (Carfilzomib for Injection) in Patients With Hematological Malignancies
A Phase I Study of the Safety and Pharmacokinetics of Escalating Intravenous Doses of the Proteasome Inhibitor PR-171 in Patients With Hematological Malignancies

The purpose of this study is to test the safety of an investigational new drug called PR-171 at different dose levels on hematological cancers such as Multiple Myeloma, Non-hodgkin's Lymphoma, Hodgkin's Disease, or Waldenstrom's Macroglobulinemia. PR-171 is a proteasome inhibitor, an enzyme responsible for degrading a wide variety of cellular proteins.

Not Provided
Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Waldenstrom's Macroglobulinemia
  • Drug: PR-171 for injection (carfilzomib)
    IV push twice weekly for 3 weeks of a 28 day cycle.
    Other Name: carfilzomib
  • Drug: Dexamethasone
Experimental: PR-171 (carfilzomib) with dexamethasone

Carfilzomib will be administered by intravenous bolus twice weekly for 3 weeks on Days 1, 2, 8, 9, 15, and 16 in a 4-week cycle with a starting dose of 1.2 mg/m2.

PR-171 (carfilzomib) +Dex Expansion Cohort:

Patients will also receive 40 mg oral dexamethasone on Days 1-4 and 15-18 in a 4-week cycle.

Dose Escalation Phase:

Cohorts of 3 patients will receive carfilzomib in a dose-escalating fashion.

PR-171 (carfilzomib) + Dex Expansion Cohort:

Patients will receive carfilzomib at the MTD on Days 1, 2, 8, 9, 15, and 16 and dexamethasone as an oral dose of 40 mg on Days 1-4 and 15-18.

Interventions:
  • Drug: PR-171 for injection (carfilzomib)
  • Drug: Dexamethasone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
48
September 2010
October 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Written informed consent in accordance with federal, local, and institutional guidelines
  2. Males and females ≥18 years of age
  3. Histologically confirmed diagnosis of one of the hematologic malignancies below:

    Waldenström's Macroglobulinemia

  4. Subjects who are refractory or relapsed following at least two prior therapies
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 2 (See Appendix 6: ECOG Performance Status subjects with ECOG of 3 based solely on bone pain may be included)
  6. Adequate cardiovascular function without symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months
  7. Adequate hepatic function, with bilirubin <2.0 times the upper limit of normal, and AST and ALT of <3.0 times the upper limit of normal
  8. Total WBC count ≥ 2,000/mm3, ANC ≥ 1000/mm3, hemoglobin ≥8.0 g/dL, and platelet count ≥50,000/mm3

    • Screening ANC should be independent of G-CSF or GM-CSF support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks)
    • Subjects receiving supportive care including erythropoietin, darbepoetin and/or bisphosphonates can continue to do so, but must be transfusion independent; subjects receiving erythropoietic support must remain on the same dose for the first 28 days of study participation
  9. An estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockroft and Gault (140-Age)X Mass (kg)/(72 X creatinine mg/dL) X 0.85 (if female)
  10. Serum creatinine ≤ 2.0 mg/dL
  11. Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing
  12. Female subjects of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test. Male subjects must use an effective barrier method of contraception throughout the study and for three months following the last dose if sexually active with a female of child-bearing potential.

Exclusion Criteria:

  1. Female subjects who are pregnant or lactating
  2. Subjects who are transfusion dependent
  3. Subjects with NHL or HL who have received steroid therapy in the previous seven days
  4. Subjects with MM or Waldenström's Macroglobulinemia who have received steroid therapy in the previous three weeks, except for MM subjects in the Carfilzomib + DEX Expansion Cohort, where previous treatment with dexamethasone will be allowed. The dose and schedule of administration of dexamethasone will be adjusted to that used in the protocol
  5. Radiation, chemotherapy, or immunotherapy in the previous four weeks, or subjects who, in the judgment of the Investigator, have not recovered from the effects of previous therapy
  6. For the Dose Escalation period, subjects who have received prior radioimmunotherapy with anti-CD20 monoclonal antibodies such as Bexxar® or Zevalin®; subjects treated with these products will be allowed in the Dose Expansion period
  7. Subjects who have received allogeneic stem cell transplant therapy
  8. Subjects with NHL or HL who have received autologous stem cell transplant therapy and have relapsed within 100 days of therapy
  9. Rituxan therapy within three months before Day 1 unless there is evidence of disease progression
  10. Major surgery within three weeks before Day 1
  11. Congestive heart failure (CHF) (New York Heart Association class III to IV)
  12. Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
  13. Subjects who are known or suspected of having HIV infection or who are HIV seropositive
  14. Active hepatitis A, B, or C infection; or positive for Hep C RNA or hepBsAG
  15. Non-hematologic malignancy within the past three years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer with stable prostate specific antigen (PSA) levels for three years
  16. Subjects with treatment-related myelodysplastic disorder
  17. Subjects with known brain metastasis (active CNS disease only)
  18. Serious psychiatric or medical conditions that could interfere with treatment
  19. Participation in an investigational therapeutic study within one month prior to Day 1
  20. Significant neurotoxicity (Grade 2 or higher with pain) at the time of study initiation
  21. Concurrent therapy with approved or investigative anticancer therapeutics
  22. Subjects with previous hypersensitivity to bortezomib injection
  23. Subjects with contraindications to receiving allopurinol
  24. Subjects in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment
  25. Subjects with known or suspected amyloidosis
  26. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00150462
PX-171-002
No
Onyx Pharmaceuticals
Onyx Pharmaceuticals
Not Provided
Study Director: Mai Le, MD Onyx Pharmaceuticals
Onyx Pharmaceuticals
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP