Status:
UNKNOWN
Safety, Efficacy, and Pharmacodynamics of a 60-Minute Infusion of Carfilzomib for Progressive Multiple Myeloma
Lead Sponsor:
Oncotherapeutics
Collaborating Sponsors:
Amgen
Conditions:
Multiple Myeloma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
This is a Phase 1/2, multicenter, open label, dose-escalation, nonrandomized study to evaluate the safety, pharmacodynamics, and efficacy of a 60-minute infusion of carfilzomib for patients with progr...
Detailed Description
This is a Phase 1/2, multicenter, open label, dose-escalation, nonrandomized study to evaluate the safety, pharmacodynamics, and efficacy of a 60-minute infusion of carfilzomib for patients with progr...
Eligibility Criteria
Inclusion
- MM with relapsing or progressive disease at study entry
- a. Defined as progressive MM on patient's last treatment regimen
- Measurable disease, as defined by one or more of the following (assessed within 14 days prior to first dose):
- Serum M-protein ≥ 0.5 g/dL, or
- Urine M-protein ≥ 200 mg/24 hours, or
- 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/lamda ratio
- Age ≥ 18 years
- Life expectancy ≥ 6 months
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Adequate hepatic function within 14 days prior to first dose, with bilirubin \< 1.5 × the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 × ULN
- LVEF ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available.
- Absolute neutrophil count (ANC) ≥ 1000/mm3 within 14 days prior to first dose. Screening ANC is to be independent of granulocyte colony stimulating factor support for ≥ 1 week and pegylated granulocyte colony stimulating factor for ≥ 2 weeks.
- Hemoglobin ≥ 8.0 g/dL within 14 days prior to enrollment. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed.
- Platelet count ≥ 75,000/mm3 (≥ 50,000/mm\^3 if myeloma involvement in the bone marrow is \> 50%) within 14 days prior to first dose. Patients must not have received platelet transfusions for at least 7 days prior to obtaining the screening platelet count
- Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min within 14 days prior to first dose. Calculation are based on a 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
- Written informed consent in accordance with federal, local, and institutional guidelines
- Female patients of childbearing potential (FCBP) must have a negative serum pregnancy test within 14 days prior to first dose 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
- 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 a FCBP
Exclusion
- Multiple myeloma of IgM subtype
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia (\> 2.0 × 109/L circulating plasma cells by standard differential)
- Waldenström's macroglobulinemia
- Amyloidosis
- Glucocorticoid therapy (prednisone \> 30 mg/day or equivalent) within 7 days prior to first dose
- Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to first dose
- Treatment with bortezomib, thalidomide or lenalidomide within 21 days prior to first dose
- Focal radiation therapy within 7 days prior to first dose. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to enrollment (i.e., prior radiation must have been to \< 30% of the bone marrow)
- Immunotherapy within 21 days prior to first dose
- Major surgery within 21 days prior to first dose
- 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 first dose.
- Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at HBV), or antifungal agents within 14 days prior to first dose
- Known human immunodeficiency virus (HIV) seropositivity
- Known hepatitis B or C virus infection (except for patients with HBV receiving and responding to HBV antiviral therapy: these patients are allowed)
- Patients with known cirrhosis
- Second malignancy within the past 3 years, except:
- Adequately treated basal cell or squamous cell skin cancer
- Carcinoma in situ of the cervix
- Prostate cancer \< Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
- Breast carcinoma in situ with full surgical resection
- Treated medullary or papillary thyroid cancer
- Patients with myelodysplastic syndrome
- Significant neuropathy (Grades 3 to 4) within 14 days prior to first dose
- Peripheral neuropathy with pain ≥ G2 within 14 days prior to first dose
- Female patients who are pregnant or lactating
- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
- Prior carfilzomib treatment
- Prior participation in any Onyx-sponsored phase 3 trial
- Patients with contraindication to dexamethasone
- 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
- Ongoing graft-versus-host disease
- Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment
- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment
- 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
Key Trial Info
Start Date :
April 1 2013
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 1 2018
Estimated Enrollment :
38 Patients enrolled
Trial Details
Trial ID
NCT01792102
Start Date
April 1 2013
End Date
December 1 2018
Last Update
March 5 2018
Active Locations (2)
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1
James R. Berenson M.D. Inc.
West Hollywood, California, United States, 90069
2
John Theuer Cancer Center Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601