Oral Oprozomib in combination with oral dexamethasone in Relapsed and/or Refractory Multiple Myeloma
- Conditions
- Relapsed and/or Refractory Multiple MyelomaMedDRA version: 17.1 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-001169-18-FR
- Lead Sponsor
- Onyx Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 128
1. Diagnosis of multiple myeloma with measureable disease as indicated by 1 or more of the following:
a. Serum M-protein = 500 mg/dL.
b. Urine M-protein = 200 mg/24 hour.
c. Serum free light chain: Involved free light chain (FLC) level = 10 mg/dL provided serum FLC ratio is abnormal.
2. Patients requiring therapy who have relapsed and/or are refractory to their last therapy and have been treated with at least 1, but not more than 5 lines of multiple myeloma therapy. Prior therapy must consist of at least 1 regimen that included lenalidomide and/or bortezomib. Patients should be considered to be an appropriate candidate for a clinical trial by their treating physician. Relapsed patients must have previously achieved = MR on at least 1 line of therapy as assessed by the treating physician. Refractory patients are allowed, but it is not required that patients be refractory to their last therapy. Primary refractory patients are allowed in the Phase 1b portion of the study only.
3. Males and females = 18 years of age.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0–2.
5. Adequate hepatic function, with bilirubin = 1.5 times the upper limit of normal (ULN) in the absence of Gilbert’s disease or hemolysis, aspartate aminotransferase (AST) = 3 times ULN, and alanine aminotransferase (ALT) = 3 times ULN.
6. Absolute neutrophil count (ANC) = 1000 cells/mcL, hemoglobin = 7.0 g/dL, and platelet count = 30,000 cells/mcL.
a. Patients must not have received platelet transfusions for at least 1 week prior to Screening.
b. Screening ANC must be independent of granulocyte- and granulocyte/macrophage colony-stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for = 2 weeks.
c. Patients may receive red blood cell (RBC) transfusions or receive supportive care with erythropoietin or darbepoetin in accordance with institutional guidelines.
7. Calculated or measured creatinine clearance (CrCL) rate of = 30 mL/min calculated using the formula of Cockcroft and Gault [(140 – age) × mass (kg) / (72 × serum creatinine mg/dL)]. Multiply result by 0.85 if female.
8. Patients must sign written informed consent form (ICF) in accordance with federal, local, and institutional guidelines.
9. Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to receiving the first dose and agree to use effective methods of contraception during the study and for 3 months following the last dose of study drug. Postmenopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for 3 months following the last dose if sexually active with a female of childbearing potential.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15
1. Radiation therapy within 2 weeks prior to first dose. Localized radiation therapy within 1 week prior to first dose.
2. Immunotherapy/standard myeloma therapy within 2 weeks prior to first dose (except for antibody therapy, where 6 weeks is required and alkylator therapy, where 3 weeks is required); prior stem cell transplant (SCT) therapy (autologous SCT within the prior 8 weeks; allogeneic SCT within the prior 16 weeks). Patients with prior allogeneic SCT should not have evidence of moderate-to-severe graft-versus-host disease (GvHD).
3. Glucocorticoid therapy within 14 days prior to randomization that exceeds a cumulative dose of 160 mg of dexamethasone or equivalent.
4. Participation in an investigational therapeutic study within 3 weeks prior to first dose.
5. Patients who failed to respond to carfilzomib defined as not having achieved = PR during therapy.
6. Carfilzomib exposure within 6 months prior to first dose
7. Prior oprozomib exposure.
8. Major surgery within 3 weeks prior to first dose.
9. Congestive heart failure ([CHF] New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to first dose.
10. Uncontrolled hypertension or uncontrolled diabetes.
11. Active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose.
12. Known or suspected human immunodeficiency virus (HIV) infection or patients who are HIV seropositive.
13. Active hepatitis A, B, or C infection.
14. Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose.
15. Other malignancy within the past 3 years with the exception of adequately treated basal cell carcinoma of the skin, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, carcinoma in situ of the breast, prostate cancer of Gleason Score 6 or less with stable prostate specific antigen levels, or cancer considered cured by surgical resection.
16. Plasma cell leukemia.
17. Female patients who are pregnant or nursing.
18. Any clinically significant psychiatric or medical condition that in the opinion of the investigator could increase patient risk, interfere with protocol adherence or a patient’s ability to give informed consent.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method