Patients aged = 65 years or younger not eligible for transplantation affected by newly diagnosed Multiple Myeloma MedDRA version: 17.1 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Code: MLN9708
Pharmaceutical Form: Capsule
INN or Proposed INN: Ixazomib citrate
CAS Number: 1239908-20-3
Current Sponsor code: MLN9708
Other descriptive name: MLN9708
Concentration unit: mg m
Sponsors
Dipartimento di Biotecnologie Molecolari e Scienze per la Salute Università degli Studi di Torino
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patient is willing and able to comply with the protocol requirements. • Patient has given voluntary written informed consent. • Female patient is either post-menopausal or surgically sterilized or willing to use two acceptable methods of birth control for the duration of the study. • Male patient agrees to use an acceptable method for contraception for the duration of the study. • Newly diagnosed MM based on standard CRAB criteria. • Age = 65 years old or younger not eligible for transplantation. • Patient with measurable disease (definitions described in study protocol) • Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2 • Clinical laboratory values within 30 days of enrolment: - platelet count = 75 x 109/mm3 (Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment) - haemoglobin = 8 g/dL - absolute neutrophil count (ANC) = 1.0 x109/mm3 - AST and ALT = 3 times the upper limit of normal - total bilirubin = 1.5 times the upper limit of normal - clearance creatinine = 30 ml/min 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 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 215
Exclusion criteria
Exclusion criteria: • Pregnant or lactating females. • Serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from the enrolment or place the subject at unacceptable risk. • Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid < to the equivalent of dexamethasone 40 mg/day for 4 days) • Clinical active infectious hepatitis type A, B, C or HIV (HBV-DNA and HCV-RNA will be analysed to evaluate the cell proliferation of virus; anti-HIV antibody must be negative). • Acute active infection requiring antibiotics or infiltrative pulmonary disease. • Peripheral neuropathy or neuropatic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 4.03. • Contraindication to any of the required drugs or supportive treatments • Invasive malignancy within the past 3 years • Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), 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 the first dose of study treatment (see Appendix 12.12). • Diagnosis of Waldenstrom’s macroglobulinemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome. • 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. • Known allergy to any of the study medications, their analogues, or excipients in the various formulations.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective: - To select the more promising association(s) among four induction treatments, followed by maintenance with MLN9708, including: o MLN9708 plus dexamethasone (MLN-DEX) o MLN9708 plus dexamethasone and cyclophosphamide (MLN-CYCLO-DEX) o MLN9708 plus dexamethasone and bendamustine (MLN-BENDA-DEX) o MLN9708 plus dexamethasone and thalidomide (MLN-THAL-DEX) in terms of Progression Free Survival (PFS) at 2 years from diagnosis.;Secondary Objective: To compare the four induction treatments, followed by maintenance with MLN9708, in terms of: - response rate (VGPR) - toxicity (rate of hematologic and non-hematologic adverse events) - progression-free survival-2 (PFS2) - time to progression (TTP) - time to next therapy (TNT) - overall survival (OS);Primary end point(s): The primary endpoint is the choice, among the four arms, of the best combination, followed by MLN9708 maintenance period, according to progression-free survival (PFS) at two years from diagnosis.;Timepoint(s) of evaluation of this end point: 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy parameters include response rate (VGPR) progression free survival at second progression (PFS2), time to progression (TTP), time to next therapy (TNT) and overall survival (OS). PFS is defined as the time from the date of enrollment to the date of second documented PD or death. TTP is defined as the time from the date of enrollment to the date of first documentation of PD. TNT is defined as the time interval from the date of enrollment to the date of subsequent antineoplastic therapy. Treatment-free interval is defined as the time interval from the date of last dose of any study drug to the date of subsequent antineoplastic therapy.;Timepoint(s) of evaluation of this end point: Every 5 patients | — |
Countries
Germany, Italy
Contacts
Public ContactPaola Minguzzi
Cronos Ricerche Cliniche srl
Outcome results
None listed