Carfilzomib, Lenalidomide and Dexamethasone versus Lenalidomide and Dexamethasone in High- Risk Smoldering Multiple Myeloma.

Phase 1

Conditions: Smoldering multiple myeloma
MedDRA version: 20.0Level: LLTClassification code 10075894Term: Smoldering myelomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2017-000555-10-IT

Lead Sponsor: HOVO

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 120

Inclusion Criteria

• Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma based on the 2014 International Myeloma Working Group Criteria:
- Serum M-protein =3 g/dl Or urinary monoclonal protein >500 mg per 24 hours And/or monoclonal bone marrow plasma cells =10-60 %
- Absence of CRAB symptoms and myeloma defining events.
• Patients must have high risk Smoldering Multiple Myeloma based on the Mayo Clinic and/or the PETHEMA criteria
• Measurable disease
• Age >18 years
• WHO/ECOG performance status <=2
• Patients must have normal organ and marrow function
• Calculated Creatinine Clearance = 50 ml/min
• Females of childbearing potential must have a negative serum or urine pregnancy test within 10 - 14 days prior to entry and again within 24 hours of starting lenalidomide treatment
• Patients must be willing and capable to use adequate contraception during and after the therapy (all men, all pre-menopausal women) Patients must be able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Plan
• Written informed consent
• Patient is capable of giving informed consent
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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

• Patients with symptomatic multiple myeloma (i.e. having myeloma defining events)
• Amyloid Light-chain (AL) amyloidosis
• Patients who are receiving any other investigational agents
• Concurrent systemic treatment or prior therapy within 4 weeks for SMM
• Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy
• History of allergic reactions attributed to immunomodulatory agents and proteasome inhibitors
• Uncontrolled hypertension or diabetes
• Pregnant or lactating females.
• Significant cardiovascular disease with NYHA grade III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia
• Active hepatitis B or C infection
• Known or suspected HIV infection
• Incidence of gastrointestinal disease that would prevent absorption
• Significant neuropathy =Grade 3 or grade 2 with pain within 14 days of enrollment
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection
• History of other malignancy (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma) except if the patient has been free of symptoms and without active therapy during at least 5 years
• Major surgery within 1 month prior to enrollment
• Pre-existing pulmonary, cardiac or renal impairement that prevents hydration measures
• Any psychological, 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
Main Objective: The primary objectives of the study are to: (a) to assess the progression-free survival rate of KRd versus Rd in patients with high-risk SMM.;Secondary Objective: • To assess MRD status after 4 and 9 cycles induction treatment<br>• To assess the correlation between PFS and MRD<br>• To determine progression-free survival-2 (PFS2 )<br>• To determine duration of response (DOR)<br>• To determine overall survival (OS)<br>• To assess correlation of MRD status with PFS2, DOR and OS<br>• To evaluate toxicity of combination therapy (carfilzomib, lenalidomide, and dexamethasone)<br>• To evaluate disease heterogeneity in relation to clinical outcomes (molecular profiling on bone marrow samples);Primary end point(s): Progression-free survival rate, defined as time from study entry to progression or death, whichever comes first;Timepoint(s) of evaluation of this end point: The endpoints will be evaluated when data of all patients are available

Secondary Outcome Measures

Name	Time	Method

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