Ixazomib citrate-thalidomide-low dose dexamethasone induction followed by maintenance therapy with ixazomib citrate or placebo in newly diagnosed multiple myeloma patients not eligible for autologous stem cell transplantation; a randomized phase II trial
- Conditions
- Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-003266-14-SE
- Lead Sponsor
- HOVON Foundation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 142
-Previously untreated patients with a confirmed diagnosis of symptomatic multiple myeloma according to IMWG criteria
- Measurable disease according to the IMWG criteria
-Age = 66 years or patients = 65 years not eligible for ASCT
- WHO performance status 0-3 for patients <75 years and WHO performance status 0-2 for patients = 75 years
-Absolute neutrophil count (ANC) = 1.0 x109/l and platelet count = 75x109/l , unless related to bone marrow infiltration by malignant plasmacells.
Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
-Written informed consent.
- Patient gives consent for extra bone marrow and blood sampling
-Negative pregnancy test at study entry or at least 1 year post-menopausal or surgically sterile before study entry
-A female patient of childbearing potential, agrees to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, AND must also adhere to the guidelines of any treatment-specific pregnancy prevention program (for thalidomide) OR agrees to completely abstain from heterosexual intercourse. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.)
-Male patients, even if surgically sterilized, (i.e., status post vasectomy) must agree to practice effective barrier contraception during the entire study period and through 90 days after the last dose of study drug, AND must also adhere to the guidelines of any treatment-specific pregnancy prevention program (for thalidomide), OR agrees to completely abstain from heterosexual intercourse (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
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 22
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
- Systemic AL amyloidosis
- Polyneuropathy, grade 3 or higher or grade 2 with pain on clinical examination during the screening period
- Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
- Severe pulmonary dysfunction (Modified Medical Research Counsil dyspnea scale classification III-IV)
- Significant hepatic dysfunction (total bilirubin = 1.5 x ULN or transaminases = 3 times normal level), except patient’s with Gilbert’s syndrome as defined by > 80% unconjugated bilirubin
- Creatinine clearance <30 ml/min or Calculated Glomerular Filtration Rate [ml/min/1.73m2] <30.
- 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 registration in the study
- Pre-treatment with cytostatic drug, IMIDs or proteasome inhibitors. Radiotherapy or a short course of steroids (e.g. 4 day treatment of dexamethasone 40 mg/day or equivalent) are allowed. Radiotherapy should not be given within 14 days before enrollment. In case of radiotherapy, if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib citrate
- Not able and/or not willing to use adequate contraception
- Female patients who are lactating or have a positive serum pregnancy test during the screening period,
- Major surgery within 14 days before enrollment.
- Central nervous system involvement.
- Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
- Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 ixazomib citraat including difficulty swallowing.
- Diagnosed or treated for another malignancy within 2 years before study enrollment 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 complete resection.
- Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21days of the start of this trial and throughout the duration of this trial.
- Any serious medical or psychiatric illness, or familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
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