This trial is active, not recruiting.

Condition multiple myeloma
Treatment carfilzomib
Phase phase 2
Target proteasome
Sponsor Onyx Therapeutics, Inc.
Start date September 2007
End date November 2011
Trial size 155 participants
Trial identifier NCT00530816, PX-171-004


Approximately 155 evaluable subjects with relapsed multiple myeloma will be enrolled to evaluate the best overall response rate, safety and tolerability of carfilzomib in this phase 2 study. Patients must have previously received one to three prior therapies and were relapsed to the most recently received therapy.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
In Cycle 1, subjects will receive carfilzomib 20 mg/m2 IV on Days 1, 2, 8, 9, 15, and 16. If all doses are administered and well-tolerated over the 28-day cycle beginning with Cycle 2 the dose will escalate to 27 mg/m2 IV on Days 1, 2, 8, 9, 15, and 16 for all subsequent cycles.
IV push twice weekly for three weeks followed by 12 days of rest. 28 days = 1 cycle. A maximum of 12 cycles will be administered.

Primary Outcomes

Best Overall Response Rate
time frame: 2 to 12 months

Secondary Outcomes

Safety and Tolerability, Clinical Benefit Response, Time to Progression, Duration of Response, Progression Free Survival, best Overall Response Rate throughout the study, and Overall Survival
time frame: 2 to 12 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: Disease Related - Multiple myeloma - Subjects must have measurable disease, defined as one or more of the following: - Serum M-protein ≥ 1 g/dL - Urine M-protein ≥ 200 mg/24 hours - Subjects must have been responsive (i.e., achieve an MR or better) to standard, first line therapy - Relapsed and/or refractory or progressive disease after at least one, but no more than three, prior therapeutic treatments or regimens for multiple myeloma. Refractory disease is defined as ≤ 25% response or progression during therapy or within 60 days after completion of therapy. Induction therapy and stem cell transplant will be considered as one regimen Demographic - Males and females ≥18 years of age - Life expectancy of more than three months - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 Laboratory - 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 - Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing - Total WBC count ≥ 2,000/mm3, absolute neutrophil count > 1,000/mm3, hemoglobin ≥ 8.0 g/dL, and platelet count > 50,000/mm3 - Subjects should be platelet transfusion independent - Screening ANC should be independent of G-CSF or GM-CSF support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks - Subjects may receive RBC transfusion or receive supportive care such as erythropoietin and darbepoetin in accordance with institutional guidelines - Calculated or measured creatinine clearance of ≥ 30 mL/minute, calculated using the formula of Cockcroft and Gault [(140 - Age) X Mass (kg) / (72 X Creatinine mg/dL)]. Multiply result by 0.85 if female. - Serum creatinine ≤ 2 mg/dL Ethical / Other - Written informed consent in accordance with federal, local, and institutional guidelines - 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. Male subjects must use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a female of child-bearing potential. - Subjects must be able to receive outpatient treatment and laboratory monitoring at the institute that administers agent. Exclusion Criteria: Disease Related - Multiple Myeloma IgM - Subjects previously treated with any proteasome inhibitor (under Amendment 2) - Subjects must not be primary refractory to standard first-line therapy - Subjects with non-secretory multiple myeloma, defined as < 1 g/dL M-protein in serum, < 200 mg/24 hr M-protein in urine - Subjects with disease measurable only by serum free light chain (SFLC) analysis - Glucocorticoid therapy (prednisone >10 mg/day orally or equivalent) within the last three weeks - POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) - Plasma cell leukemia - Chemotherapy with approved or investigative anticancer therapeutics, including steroid therapy, within the three weeks prior to first dose - Radiation therapy or immunotherapy in the previous four weeks; localized radiation therapy within 1 week prior to first dose - Participation in an investigational therapeutic study within three weeks or within five drug half-lives (t1/2) prior to first dose, whichever time is greater - Prior treatment with carfilzomib Concurrent Conditions - Major surgery within three weeks before Day 1 - Congestive heart failure (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months - Acute active infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first dose - Known or suspected HIV infection or subjects who are HIV seropositive - Active hepatitis A, B, or C infection - 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 < Gleason Grade 6 with stable PSA - Subjects with treatment related myelodysplastic syndrome - Significant neuropathy (Grade 3, 4 or Grade 2 with pain) at the time of study initiation - Subjects with known contraindication 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 - Any clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent Ethical / Other - Female subjects who are pregnant or lactating - Serious psychiatric or medical conditions that could interfere with treatment

Additional Information

Official title An Open-Label, Single-Arm, Phase 2 Study of Carfilzomib in Patients With Relapsed Multiple Myeloma
Trial information was received from ClinicalTrials.gov and was last updated in August 2012.
Information provided to ClinicalTrials.gov by Onyx Pharmaceuticals.