Carfilzomib, Lenalidomide and Dexamethasone versus Lenalidomide and Dexamethasone in High- Risk Smoldering Multiple Myeloma: A Randomized Phase 2 Study

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 25

Inclusion Criteria

• Patients must have histologically or cytologically confirmed Smoldering
Multiple Myeloma based on the 2014 International Myeloma Working Group Criteria:
o Serum M-protein >=3 g/dl
Or urinary monoclonal protein >500 mg per 24 hours
And/or monoclonal bone marrow plasma cells >=10-60 %
o 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

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.
• Hypersensitive reaction to active substances or any excipients of the IMPs
• 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
• Patients with gastric or duodenal ulcers
• 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

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>• MRD negativity rate by NGF after cycle 9 for all eligible ITT patients;<br /><br>eligible patients who achieve a MRD negativity after cycle 9 will be considered<br /><br>as a success. All other eligible randomized ITT patients will be considered as<br /><br>a failure, including patients going off-protocol before cycle 9, whatever the<br /><br>cause.</p><br>

Secondary Outcome Measures

Name	Time	Method

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