A Phase 3 interventional study of Carfilzomib and Lenalidomide in Multiple Myeloma and New Diagnosis Tumor, sponsored by Fondazione EMN Italy Onlus. Active, not recruiting at 40 sites in Italy. Open to participants aged 65 Years and older. Per ClinicalTrials.gov, last updated 2026-09-21.
Sponsored by Fondazione EMN Italy Onlus · Phase 3, Interventional, and Treatment
The combination of lenalidomide plus low-dose dexamethasone (Rd) is considered the new standard for elderly newly diagnosed multiple myeloma (NDMM) patients. The combination carfilzomib plus lenalidomide-dexamethasone (KRd) in relapsed-refractory MM patients improved the progression-free survival (PFS) of approximately 1 year compared to standard Rd treatment. In a small phase 2 trial (23 pts) the KRd combination in elderly NDMM pts showed a complete response (CR) rate of 79% and a PFS at 3 years of 80%. Cardiovascular adverse events are the most limiting toxicities, especially in elderly patients.
This protocol is a randomized, multicenter study designed to determine the MRD negativity and the PFS of KRd treatment regimen.
Patients will be randomized in a 1:1 ratio to receive carfilzomib-lenalidomide-dexamethasone (KRd - Arm A) or lenalidomide-dexamethasone (Rd - Arm B).
Patients will be stratified basing on international staging system (ISS) and fitness status using a web-based procedure completely concealed to study participants.
All consecutive patients ≥ 65 years with newly diagnosed MM will be enrolled in a large randomized study during a period of 24 months.
Patients will be treated until disease progression or intolerance to the therapy. The only exception is for patients enrolled in KRd arm who achieve at least a VGPR during the first year of treatment and in sustained MRD negativity (MRD negative at least at 10-5 after one and two years of therapy): these patients will stop carfilzomib administration after 2 years, whereas treatment with lenalidomide and dexamethasone will be continued.
Newly diagnosed symptomatic MM based on either standard CRAB criteria (at least 10% of clonal bone marrow plasma cells plus CRAB defined as the onset of any of the following clinical symptoms: hypercalcemia, renal failure, anemia and bone lesions) or at least 10% of bone marrow plasma cells plus the presence of at least one of the following biomarkers of malignancy:
Pre-treatment clinical laboratory values within 30 days before randomization:
Exclusion Criteria:
Presence of:
Carfilzomib (K): * 20 mg/m2 IV on day 1 of cycle 1; * 56 mg/m2 IV on days 8 and 15 in cycle 1; * 56 mg/m2 IV on days 1, 8 and 15 in cycles 2-12; * 56 mg/m2 on days 1 and 15 from cycle 13 and onwards. Lenalidomide (R): \- 25 mg orally on days 1-21 of each cycle. Dexamethasone (d): \- 40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycle. Until PD or intolerance. Only patients that achieve at least a VGPR within the first year of treatment and in sustained MRD negativity (MRD negative at least at 10-5 after 1 and 2 years of therapy) will stop carfilzomib after 2 years of treatment, and will continue with lenalidomide and dexamethasone administration.
Drug: Carfilzomib · Drug: Lenalidomide · Drug: Dexamethasone
Lenalidomide (R): -25 mg orally on days 1-21 of each cycle. Dexamethasone (d): -40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycles. Until PD or intolerance.
Drug: Lenalidomide · Drug: Dexamethasone
* 20 mg/m2 IV on day 1 of cycle 1 enhanced to 56 mg/m2 on days 8, and 15 of cycle 1; * 56 mg/m2 IV on days 1, 8 and 15 in cycles 2-12; * 56 mg/m2 IV on days 1 and 15 from cycle 13 and onwards.
Also known as: Kyprolis
\- 25 mg orally on days 1-21 of each cycle.
Also known as: Revlimid
\- 40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is to be repeated every 28 days. Patients that achieve at least a VGPR within the first year of study treatment and in sustained MRD negativity (MRD negative at least at 10-5 after 1 and 2 years of therapy) will stop carfilzomib administration after 2 years and will continue with lenalidomide and dexamethasone treatment until disease progression or intolerance to the therapy. Other patients will continue carfilzomib administration until disease progression or intolerance. For patients \>75 years of age, the dose of dexamethasone is 20 mg/day on Days 1, 8, 15 and 22 of each treatment cycle.
Minimal residual disease (MRD)
1\. Minimal residual disease (MRD): unit of measure is not applicable, MRD is expressed as a pure number
Time frame: 5 years
Progression-free survival (PFS)
2\. Progression-free survival (PFS): unit of measure is not applicable, PFS is expressed as a pure number
Time frame: 5 years
Rate of drug reduction or drug discontinuation
Incidence of dose reduction and drug discontinuation in both treatment arms.
Time frame: 5 years
Cardiovascular assessment
Benefit of proper cardiovascular baseline assessment and monitoring during treatment in both treatment arms:to mitigate major cardiovascular adverse event incidence, to prolong duration of treatment, to improve efficacy.
Time frame: 5 years
Rate of dose reduction, drug discontinuation and toxicities
Safety as rate of dose reduction, drug discontinuation and toxicities
Time frame: 5 years
Response rate
Response rate will include complete response (CR), very good partial response (VGPR) and partial response (PR) using the International Response Criteria. Responders are defined as subjects with at least a PR.
Time frame: 5 years
Progression-free survival 2 (PFS2)
Time from randomization to objective tumor progression on next-line treatment or death from any cause.
Time frame: 5 years
Time to progression (TTP)
Time to progression will be measured from the date of randomization to the date of first observation of PD, or deaths related to PD.
Time frame: 5 years
Duration of response (DOR)
Time between first documentation of response and PD. Responders without disease progression will be censored either at the time of lost to FU, at the time of death due to other cause than PD, or at the end of the study.
Time frame: 5 years
Overall survival (OS)
Time between randomization and death. Subjects who die will be censored at time of death as an event, regardless cause of death.
Time frame: 5 years
Time to next therapy (TNT)
Time to next therapy will be measured from the date of randomization to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event.
Time frame: 5 years
MRD negativity
Correlation between MRD negativity and PFS, PFS2, TTP, TNT and OS
Time frame: 5 years
Prognostic factors
The following outcomes will be analysed in subgroups with different prognostic factors: * Progression-free survival (PFS), * Time to second disease progression (PFS2), * Time to progression (TTP), * Time to next therapy (TNT ), * Overall survival (OS)
Time frame: 5 years
This study is active, not recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.
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Fondazione EMN Italy Onlus