Study to determine whether adding MLN9708 to the combination of lenalidomide and dexamethasone improves survival in patients who have been newly diagnosed with multiple myeloma and have not received previous anti-myeloma treatment
- Conditions
- ewly diagnosed multiple myelomaMedDRA version: 20.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-000326-54-BE
- Lead Sponsor
- Millennium Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 701
1. Adult male or female patients 18 years old and above with a confirmed diagnosis of symptomatic multiple myeloma according to International Myeloma Working Group criteria who have not received prior treatment for multiple myeloma
2. Patients for whom lenalidomide and dexamethasone treatment is appropriate and who are not eligible for HDT-SCT for 1 or more of the following reasons:
* The patient is 65 years of age or older
* The patient is less than 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT
3. Patients must have measurable disease defined by at least 1 of the following 3 measurements:
* Serum M-protein = 1 g/dL (= 10 g/L)
* Urine M-protein = 200 mg/24 hours
* Serum free light chain assay: involved free light chain level = 10 mg/dL (= 100 mg/L), provided that the serum free light chain ratio is abnormal
4. Patients must meet the following clinical laboratory criteria:
* Absolute neutrophil count (ANC) = 1,000/mm3 and platelet count = 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days prior to randomization
* Total bilirubin = 1.5 × the upper limit of the normal range (ULN).
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 × ULN.
* Calculated creatinine clearance = 30 mL/min, , as calculated using the Cockcroft-Gault Equation
NOTE: Patients with a low creatinine clearance = 60 mL/min (or = 50 mL/min, according to local label/practice) but = 30 mL/min will receive a reduced lenalidomide dose of 10 mg once daily on Days 1 through 21 of a 28-day cycle, patients with a creatinine clearance < 30 mL/min are not permitted to be enrolled into the study. The lenalidomide dose may
be escalated to 15 mg once daily after 2 cycles if the patient is not responding to treatment and is tolerating the treatment. If renal function normalizes (ie, creatinine clearance > 60 mL/min or > 50 mL/min, according to local label/practice) and the patient continues to
tolerate this treatment, lenalidomide may then be escalated to 25 mg once daily.
5. ECOG performance status of 0, 1, or 2.
6. Female patients who:
* Are postmenopausal for at least 24 months before the Screening visit,
OR
* Are surgically sterile, OR
* Females of childbearing potential (FCBP) must:
a. All countries except Canada: Have TWO medically-supervised negative pregnancy tests (serum or urine with sensitivity of at least 25 mIU/mL), even if continuous abstinence is the chosen method of contraception. One test must be obtained within 10 to 14 days and the other test must be obtained within 24 hours prior to administering the first dose of the
study drug regimen at Cycle 1, Day 1. The dates and results of pregnancy tests must be documented
c. Either agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient (periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception) OR begin TWO reliable methods of birth control: 1 highly effective method and 1 additional effective method AT THE SAME TIME, at least 28 days before starting the study drug regimen through 90 days after the last dose of study treatment
d. Agree to ongoing pregnancy testing
e. Adhere to the guidelines of The Lenalidomide Pregnancy Risk Minimisation Plan as outlined in the Stu
1. Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen
NOTE: Prior treatment with corticosteroids or localized radiotherapy is permitted as long as it is below a therapeutic level (maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone over a 2-week period)
2. Localized radiotherapy within 14 days before randomization
3. Diagnosed and treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone histologically confirmed complete surgical resection
4. Inability or unwillingness to receive thromboembolism prophylaxis
5. Female patients who are lactating and breastfeeding or have a positive pregnancy test during the Screening period
6. Major surgery within 14 days before randomization.
NOTE: Kyphoplasty or vertebroplasty is not considered major surgery
7. Central nervous system involvement
8. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before randomization
9. Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative
syndrome.
10. Evidence of current uncontrolled cardiovascular conditions within 6 months prior to randomization, including:
• uncontrolled hypertension, cardiac arrhythmias, or congestive heart failure
• unstable angina, or
• myocardial infarction
11. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before randomization in the study
12. Ongoing or active infection, or active hepatitis B or C infection, or known human immunodeficiency virus (HIV) positive.
13. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (eg, peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of
any cause).
14. Psychiatric illness/social situation that would limit compliance with study requirements
15. Known allergy to any of the study medications, their analogues, orexcipients in the various formulations of any agent
16. Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment
17. Treatment with any investigational products within 60 days before randomization
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