A Multicenter Phase II Study. Drugs given randomly but everybody will be aware of the treatment assigned. The elderly patients affected by a newly diagnosed multiple myeloma will be divided in 4 treatment groups: MLN9708 + Oral Dexamethasone or + oral Cyclophosphamide and Dexamethssone or + Bendamustine and dexamethasone or + oral Thalidomide and Dexamethasone. At the end of the induction phase, the patients will be maintained under MLN9708 treatment up to desease progression for up to 2 years.

• Conditions: Patients aged = 65 years or younger not eligible for transplantation affected by newly diagnosed Multiple Myeloma; MedDRA version: 17.1Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2014-004859-31-IT
• Lead Sponsor: Dipartimento di Biotecnologie Molecolari e Scienze per la Salute Università degli Studi di Torino

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-12-22
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 260

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

• 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified