This trial is active, not recruiting.

Condition multiple myeloma
Treatment carfilzomib
Phase phase 1/phase 2
Target proteasome
Sponsor Onyx Therapeutics, Inc.
Start date July 2012
End date December 2016
Trial size 123 participants
Trial identifier NCT01677858, 2012-002


This is a Phase 1/2, multicenter, single-arm, nonrandomized, open-label and dose-escalation study of weekly carfilzomib and dexamethasone (Cd-qw) for patients with progressive multiple myeloma. The Phase 1 dose escalation portion will enroll patients into sequential dose-escalating cohorts consisting of 3 patients each to establish the maximum tolerated dose (MTD) of carfilzomib administered weekly as a 30 minute intravenous (IV) infusion with dexamethasone. The Phase 2 portion will enroll patients using the MTD established for carfilzomib from the Phase 1 portion of the study. Dexamethasone will be administered IV or PO at the same dose and schedule as used in the Phase 1 portion of the study.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Phase 1: Carfilzomib will be administered as a 30-minute intravenous (IV) infusion on Days 1, 8, and 15 of each 28-day cycle. On only Day 1 of Cycle 1, all patients will receive carfilzomib at 20 mg/m2. All subsequent carfilzomib doses (45, 56, 70 or 88 mg/m2) will be administered according to the dose assignment for each cohort. Phase 2: using the MTD established for carfilzomib from the Phase 1 portion of the study (except on Cycle 1 Day 1 the carfilzomib dose will be 20 mg/m2); this arm will be administered drug on the same schedule as in Phase 1.

Primary Outcomes

Phase 1: Determine the Maximum Tolerated Dose
time frame: 12 months
Phase 2: Overall Response Rate
time frame: 18 months

Secondary Outcomes

Clinical Benefit Response Rate
time frame: 18 months
Progression Free Survival
time frame: 18 months
Time To Progression
time frame: 18 months
Duration of Response
time frame: 18 months

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: 1. Multiple myeloma with relapsing or progressive disease at study entry 2. Measurable disease, as defined by 1 or more of the following (assessed within 21 days prior to enrollment): 1. Serum M-protein ≥ 0.5 g/dL, or 2. Urine M-protein ≥ 200 mg/24 hours, or 3. Only in patients who do not meet a or b, then use serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa/lambda ratio 3. Prior treatment with 1 to 3 prior regimens for multiple myeloma for Phase 1 and Phase 2 (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy 4. Age ≥ 18 years 5. Life expectancy ≥ 6 months 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 7. Adequate hepatic function within 21 days prior to enrollment, with bilirubin < 1.5 × the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 × ULN 8. Left ventricular ejection fraction (LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated acquisition scan (MUGA) is acceptable if ECHO is not available 9. Absolute neutrophil count (ANC) ≥ 1000/mm3 within 21 days prior to enrollment. Screening ANC is to be independent of growth factor support for ≥ 1 week 10. Hemoglobin ≥ 8.0 g/dL within 21 days prior to enrollment. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed; however, most recent RBC transfusion must have been at least 7 days prior to obtaining screening hemoglobin 11. Platelet count ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma involvement in the bone marrow is > 50%) within 21 days prior to enrollment. Patients must not have received platelet transfusions for at least 7 days prior to obtaining the screening platelet count 12. Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min within 21 days prior to enrollment. Calculation are to be based on standard formula, such as the Cockcroft and Gault: [(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female 13. Written informed consent in accordance with federal, local, and institutional guidelines 14. Female patients of childbearing potential (FCBP) must have a negative serum pregnancy test within 21 days prior to enrollment and agree to use an effective method of contraception during and for 3 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations). Postmenopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from a pregnancy test 15. Male patients must agree to use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with an FCBP Exclusion Criteria: 1. Multiple myeloma of IgM subtype 2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 3. Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential) 4. Waldenström's macroglobulinemia 5. Amyloidosis 6. Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to enrollment 7. Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to enrollment 8. Treatment with bortezomib (Velcade®), thalidomide (Thalomid®) or lenalidomide (Revlimid®) within 21 days prior to enrollment 9. Focal radiation therapy within 7 days prior to enrollment. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to enrollment (ie, prior radiation must have been to < 30% of the bone marrow) 10. Immunotherapy within 21 days prior to enrollment 11. Major surgery within 21 days prior to enrollment 12. Active congestive heart failure (New York Heart Association [NYHA] Classes III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to enrollment 13. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at HBV), or antifungal agents within 14 days prior to enrollment 14. Known human immunodeficiency virus (HIV) seropositivity 15. Known hepatitis B or C virus infection (except for patients with HBV who are receiving and responding to HBV antiviral therapy: these patients are allowed) 16. Patients with known cirrhosis 17. Second malignancy within the past 3 years, except: 1. Adequately treated basal cell or squamous cell skin cancer 2. Carcinoma in situ of the cervix 3. Prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months 4. Breast carcinoma in situ with full surgical resection 5. Treated medullary or papillary thyroid cancer 18. Patients with myelodysplastic syndrome 19. Significant neuropathy (Grades 3 to 4) within 14 days prior to enrollment 20. Female patients who are pregnant or lactating 21. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) 22. Prior carfilzomib treatment 23. Prior participation in any Onyx-sponsored Phase 3 trial 24. Patients with contraindication to dexamethasone 25. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment 26. Ongoing graft-versus-host disease 27. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment 28. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment 29. Any other clinically significant medical disease or psychiatric condition that, in the Investigator's opinion, may interfere with protocol adherence or a patient's ability to give informed consent

Additional Information

Official title A Phase 1/2, Multicenter, Single-arm, Nonrandomized, Open-label and Dose-escalation Study of Weekly Carfilzomib and Dexamethasone (Cd-qw) for Patients With Progressive Multiple Myeloma.
Description This Phase 1/2 study in patients with progressive multiple myeloma is designed to achieve the following: to determine the MTD of carfilzomib and dexamethasone administered once weekly (Cd-qw) for 3 consecutive weeks in a 28-day cycle and to determine the magnitude of responses achieved in patients treated with the MTD. The Cd-qw dosing schedule proposed in this protocol may be beneficial from a patient convenience perspective compared to the twice-weekly dosing schedule, however, as the clinical benefit and safety of weekly carfilzomib administration has not been assessed in multiple myeloma patients, patients who progress on weekly carfilzomib will be allowed 1 attempt to recapture response by increasing the dose frequency to the twice-weekly carfilzomib dosing schedule that has demonstrated efficacy and tolerability. This information will be valuable in assessing the dose intensity impact on the suppression of multiple myeloma in the relapsed setting. Finally, this protocol will eliminate the requirement for fluid administration with carfilzomib after Cycle 1 and will reduce the time that is required to treat the patient in clinic. This modification will be studied for its effect on the carfilzomib safety profile.
Trial information was received from ClinicalTrials.gov and was last updated in April 2016.
Information provided to ClinicalTrials.gov by Onyx Pharmaceuticals.