Safety Study of the Proteasome Inhibitor PR-171 (Carfilzomib for Injection) in Patients With Hematological Malignancies
This study has been completed.
Sponsor:
Onyx Pharmaceuticals
Information provided by (Responsible Party):
Onyx Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00150462
First received: September 6, 2005
Last updated: August 30, 2011
Last verified: August 2011
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Purpose
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.
Condition | Intervention | Phase |
---|---|---|
Waldenstrom's Macroglobulinemia |
Drug: PR-171 for injection (carfilzomib) |
Phase 1 |
Study Type: | Interventional |
Study Design: | Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
Official Title: | A Phase I Study of the Safety and Pharmacokinetics of Escalating Intravenous Doses of the Proteasome Inhibitor PR-171 in Patients With Hematological Malignancies |
Resource links provided by NLM:
Further study details as provided by Onyx Pharmaceuticals:
Primary Outcome Measures:
- 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 ]
Secondary Outcome Measures:
- To determine the pharmacodynamics (PDn) of carfilzomib. [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
Enrollment: | 48 |
Study Start Date: | September 2005 |
Study Completion Date: | September 2010 |
Primary Completion Date: | October 2009 (Final data collection date for primary outcome measure) |
Intervention Details:
-
Drug: PR-171 for injection (carfilzomib)
IV push twice weekly for three weeks 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:
- Written informed consent in accordance with federal, local, and institutional guidelines
- Males and females ≥18 years of age
Histologically confirmed diagnosis of one of the hematologic malignancies below:
Waldenström's Macroglobulinemia
- Subjects who are refractory or relapsed following at least two prior therapies
- 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)
- Adequate cardiovascular function without symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months
- 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
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
- 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)
- Serum creatinine ≤ 2.0 mg/dL
- Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing
- 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:
- Female subjects who are pregnant or lactating
- Subjects who are transfusion dependent
- Subjects with NHL or HL who have received steroid therapy in the previous seven days
- 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
- 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
- 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
- Subjects who have received allogeneic stem cell transplant therapy
- Subjects with NHL or HL who have received autologous stem cell transplant therapy and have relapsed within 100 days of therapy
- Rituxan therapy within three months before Day 1 unless there is evidence of disease progression
- Major surgery within three weeks before Day 1
- Congestive heart failure (CHF) (New York Heart Association class III to IV)
- Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
- Subjects who are known or suspected of having HIV infection or who are HIV seropositive
- Active hepatitis A, B, or C infection; or positive for Hep C RNA or hepBsAG
- 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
- Subjects with treatment-related myelodysplastic disorder
- Subjects with known brain metastasis (active CNS disease only)
- Serious psychiatric or medical conditions that could interfere with treatment
- Participation in an investigational therapeutic study within one month prior to Day 1
- Significant neurotoxicity (Grade 2 or higher with pain) at the time of study initiation
- Concurrent therapy with approved or investigative anticancer therapeutics
- Subjects with previous hypersensitivity to bortezomib injection
- Subjects with contraindications to receiving allopurinol
- 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
- Subjects with known or suspected amyloidosis
- Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00150462
Locations
United States, California | |
Tower Cancer Research Foundation | |
Beverly Hills, California, United States, 90211-1850 | |
United States, Florida | |
H. Lee Moffitt Cancer Center and Research Institute | |
Tampa, Florida, United States, 33612 | |
United States, New York | |
Memorial Sloan Kettering Cancer Center | |
New York, New York, United States, 10021 | |
Herbert Irving Comprehensive Cancer Center, Columbia University | |
New York, New York, United States, 10032 | |
Weil Medical College of Cornell University | |
New York, New York, United States, 10021 |
Sponsors and Collaborators
Onyx Pharmaceuticals
Investigators
Study Director: | Mai Le, MD | Onyx Pharmaceuticals |
More Information
No publications provided
Keywords provided by Onyx Pharmaceuticals:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on October 16, 2012
No publications provided
Responsible Party: | Onyx Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT00150462 History of Changes |
Other Study ID Numbers: | PX-171-002 |
Study First Received: | September 6, 2005 |
Last Updated: | August 30, 2011 |
Health Authority: | United States: Food and Drug Administration |
Keywords provided by Onyx Pharmaceuticals:
Hematological Proteasome Myeloma Lymphoma |
Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia Hematologic Neoplasms Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias |
Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Neoplasms by Site |
ClinicalTrials.gov processed this record on October 16, 2012