Smoldering multiple myeloma MedDRA version: 26.1 Level: LLT Classification code 10075894 Term: Smoldering myeloma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
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 =65 years) yes F.1.3.1 Number of subjects for this age range 47
Exclusion criteria
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 • Treatment with corticosteroids for other indications is not permitted • 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives of the study are to: (a) To assess MRD negativity rate by NGF after 9 cycles for all eligible ITT patients of KRd versus Rd in patients with high-risk SMM ;Secondary Objective: • To assess MRD (NGF) negativity rate after 4 cycles of induction treatment • To assess MRD (NGF) negativity rate after completion of maintenance treatment • To assess correlation of MRD (NGF) negativity rate with PFS • To assess overall response rate (ORR) after 4 and 9 cycles induction treatment and after maintenance • To determine progression-free survival (PFS) • To determine progression-free survival-2 (PFS2) • To determine duration of response (DOR) • To determine overall survival (OS) • To assess correlation of MRD (NGF) negativity rate with PFS, PFS2, DOR and OS • To evaluate toxicity of combination therapy (carfilzomib, lenalidomide, and dexamethasone) • To evaluate safety (type, frequency, and severity of adverse events (AE) and relationship of AE to study drug, serious AE (SAEs)) • To evaluate disease heterogeneity in relation to clinical outcomes (molecular profiling on bone marrow samples);Primary end point(s): MRD negativity rate by NGF after cycle 9 for all eligible ITT patients; eligible patients who achieve a MRD negativity after cycle 9 will be considered as a success. All other eligible randomized ITT patients will be considered as a failure, including patients going off-protocol before cycle 9, whatever the cause. ;Timepoint(s) of evaluation of this end point: The endpoints will be evaluated when data of all patients are available | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • MRD negativity rate evaluated by means of next generation flow cytometry (cut off 10-5) after cycle 4; • MRD negativity rate evaluated by means of next generation flow cytometry (cut off 10-5) after completion of maintenance • Correlation of MRD (NGF) negativity rate with PFS • Overall response rate (ORR; i.e. at least partial response (PR)) after 9 cycles induction treatment; • Progression-free survival (PFS), defined as time from study entry to progression or death, whichever comes first; • Progression-free survival-2 (PFS2), defined at time from randomization to progression after second-line treatment or death, whichever comes first; • Duration of response (DOR), defined as time from response to progression or death, whichever comes first; • Overall survival (OS), defined as time from study entry to death from any cause. Patients still alive at the date last contact will be censored; • Correlation of MRD (NGF) negativity rate with PFS, PFS2, DOR and OS; • Toxicity of combination therapy (carfilzomib, lenalidomide, and dexamethasone) • Safety (type, frequency, and severity of adverse events (AE) and relationship of AE to study drug, serious AE (SAEs)) • Disease heterogeneity in relation to clinical outcomes (molecular profiling on bone marrow samples);Timepoint(s) of evaluation of this end point: The endpoints will be evaluated when data of all patients are available | — |
Countries
Czechia, Czech Republic, Italy, Netherlands, Norway
Contacts
Public ContactHOVON Data Center
HOVON
Outcome results
None listed