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Multiple MyelomaPhase 3KRdvsRdNCT04096066

A Trial That Compare Two Treatments in Newly Diagnosed Myeloma Patients Not Eligible for Transplant

A Phase 3 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma and New Diagnosis Tumor, run by Fondazione EMN Italy Onlus at 40 sites in Italy.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 65 years and older
Conditions the study is for
Multiple Myeloma, New Diagnosis Tumor
What is being tested?
Carfilzomib, Lenalidomide and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
84 participants
Where
40 sitesItaly
Study dates
1 Jul 2019to 1 Sep 2027
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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:
  • 60% or greater clonal plasma cells on bone marrow examination;
  • Serum involved/uninvolved free light chain (FLC) ratio of 100 or greater;
  • More than one focal lesion on magnetic resonance imaging (MRI) that is at least 5 mm or greater in size.
  • Patient not eligible for ASCT (age ≥ 65 years or abnormal cardiac, pulmonary and liver function).
  • Patient defined as fit or intermediate according to the IMWG (International Myeloma Working Group) frailty score
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  • Patient has given voluntary written informed consent.
  • Patient is able to be compliant with hospital visits and procedures required per protocol.
  • Patient agrees to use acceptable methods for contraception.
  • Patient has measurable disease according to IMWG criteria.
  • Patient has ECOG (Eastern Cooperative Oncology Group) performance status < 3.
  • Pre-treatment clinical laboratory values within 30 days before randomization:
  • Platelet count ≥50 x 109/L (≥30 x 109 /L if myeloma involvement in the bone marrow is > 50%)
  • Absolute neutrophil count (ANC) ≥ 1 x 109/L without the use of growth factors
  • Corrected serum calcium ≤14 mg/dL (3.5 mmol/L)
  • Alanine transaminase (ALT): ≤ 3 x the ULN
  • Total bilirubin: ≤ 2 x the ULN
  • Calculated or measured creatinine clearance: ≥ 30 mL/minute.
  • LVEF≥ 40%: 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation; multigated Acquisition Scan (MUGA) is acceptable if ECHO is not available
  • Pre-treatment blood pressure value < 140/90 mmHg even with adequate therapy: 24 hours blood pressure monitoring is the preferred method of evaluation; blood pressure diary at home for 2 weeks is acceptable.
  • Females of childbearing potential (FBCP) comply with the conditions of the Pregnancy Prevention Plan, including confirmation that she has an adequate level of understanding.
  • FBCP must follow the Pregnancy Prevention Plan and use a highly effective and an additional barrier contraception method simultaneously for 4 weeks before starting therapy, during treatment and dose interruptions and for at least 30 days after the last dose of study drugs*
  • Males must use an effective barrier method of contraception if sexually active with FCBP during the treatment and for at least 90 days after the last administration of study drug/s. Male subjects must agree to refrain from sperm donation for at least 90 days after the last dose of carfilzomib.

Who cannot join

  • Serious medical condition, laboratory abnormality or psychiatric illness that prevented the subject from the screening or place the subject at unacceptable risk.
  • Patient defined as frail according to the IMWG frailty score.
  • 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).
  • Pregnant or lactating females.
  • Presence of:
  • Clinical active infectious hepatitis type A, B, C or HIV
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  • Acute active infection requiring antibiotics or infiltrative pulmonary disease
  • Pulmonary hypertension and interstitial lung disease
  • Uncontrolled arrhythmias or history of QT prolongation
  • Myocardial infarction or unstable angina ≤ 6 months or other clinically significant heart disease
  • Peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 5.0 (Appendix A)
  • Uncontrolled hypertension defined as persistent hypertension (>140/90 mmHg) regardless treatment with 3 drugs, including a diuretic.
  • Contraindication to any of the required drugs or supportive treatments and hypersensitivity to any excipient of the study drugs.
  • Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib).
  • Invasive malignancy within the past 3 years.
  • Administration of any experimental drug within 4 weeks prior the baseline or within 5 drug half-lives.

Trial locations and contacts

40 sites in 1 country.

40 sites in 1 country

Italy40 sites

  • AO "SS. Antonio e Biagio"

    Alessandria

  • AOU Ospedali Riuniti Umberto I

    Ancona

  • Ospedale Mazzoni

    Ascoli Piceno

  • Policlinico di Bari

    Bari

  • Ospedali Riuniti

    Bergamo

  • Azienda Sanitaria di Bolzano - Ospedale Lorenz B:Ohler

    Bolzano

  • A.O. Spedali Civili di Brescia

    Brescia

  • Ospedale "A. Businco"

    Cagliari

  • Istituto per la Cura e la RIcerca del Cancro di Candiolo

    Candiolo

  • Ospedale Civico S. Croce e Carle

    Cuneo

  • AOU Careggi

    Florence

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)

    Meldola

  • Azienda Ospedaliera Papardo

    Messina

  • Policlinico Universitario di Messina

    Messina

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan

  • Istituto Europeo Oncologico

    Milan

  • Istituto Nazionale Tumori

    Milan

  • Ospedale Maggiore Policlinico di Milano

    Milan

  • Università Federico II-Policlinico

    Naples

  • Ospedale Maggiore

    Novara

  • AO San Luigi Gonzaga

    Orbassano

  • AO di Padova

    Padova

  • AO Cervello

    Palermo

  • Ospedale S. Maria della Misericordia

    Perugia

  • Ospedale Santa Maria delle Croci

    Ravenna

  • AO Bianchi Melacrino Morelli

    Reggio Calabria

  • Ausl-Irccs

    Reggio Emilia

  • Ospedale Infermi

    Rimini

  • Ospedale Oncologico Regionale

    Rionero in Vulture

  • ASL Roma 1

    Roma

  • Azienda Ospedaliera Universitaria Policlinico Tor Vergata

    Roma

  • Ospedale S. Eugenio - Università Tor Vergata

    Roma

  • Ospedale San Camillo Forlanini

    Roma

  • Policlinico Umberto I - Università La Sapienza

    Roma

  • Istituto Clinico Humanitas

    Rozzano

  • IRCCS Ospedale Casa Sollievo della Sofferenza

    San Giovanni Rotondo

  • AO S. Maria

    Terni

  • AOU Città della Salute e della Scienza di Torino - PO Molinette - Ematologia U

    Torino

  • AOU Città della Salute e della Scienza di Torino - PO Molinette

    Torino

  • Policlinico Universitario di Udine

    Udine

Other trials in Italy

About this study

Official title: Carfilzomib - Lenalidmide - Dexamethasone (KRd) Versus Lenalidomi - Dexamethasone (Rd) in Newly Diagnosed Myeloma Patients Not Eligible for Autologous Stem Cell Transplantation: a Randomized Phas III Trial

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.

Read the detailed description

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.

Keywords
Multiple Myeloma, AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE, Proteasome inhibitor, Immunomodulating agents
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarfilzomibDrug

    Also called Kyprolis

    • 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.

  • LenalidomideDrug

    Also called Revlimid

    • 25 mg orally on days 1-21 of each cycle.

  • DexamethasoneDrug

    • 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.

Study groups in NCT04096066
Study groupRoleWhat they receive
KRd (Experimental Arm)ExperimentalCarfilzomib (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.
Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone
Rd (Control Arm)Active comparatorLenalidomide (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.
Receives: Drug: Lenalidomide; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Minimal residual disease (MRD)

    1. Minimal residual disease (MRD): unit of measure is not applicable, MRD is expressed as a pure number

    Measured: 5 years

  2. Progression-free survival (PFS)

    1. Progression-free survival (PFS): unit of measure is not applicable, PFS is expressed as a pure number

    Measured: 5 years

Secondary outcomes (11)

  1. Rate of drug reduction or drug discontinuation

    Incidence of dose reduction and drug discontinuation in both treatment arms.

    Measured: 5 years

  2. 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.

    Measured: 5 years

  3. Rate of dose reduction, drug discontinuation and toxicities

    Safety as rate of dose reduction, drug discontinuation and toxicities

    Measured: 5 years

  4. 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.

    Measured: 5 years

  5. Progression-free survival 2 (PFS2)

    Time from randomization to objective tumor progression on next-line treatment or death from any cause.

    Measured: 5 years

  6. 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.

    Measured: 5 years

  7. 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.

    Measured: 5 years

  8. 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.

    Measured: 5 years

  9. 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.

    Measured: 5 years

  10. MRD negativity

    Correlation between MRD negativity and PFS, PFS2, TTP, TNT and OS

    Measured: 5 years

  11. 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)

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2019
  2. Study start1 Jul 2019
  3. Primary completion1 Sep 2027 (estimated)
  4. Study completion1 Sep 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04096066
Sponsor's protocol ID
EMN20
Acronym
KRdvsRd
Status last verified
Sep 2026
First submitted
2 Jul 2019
Last updated
21 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Bringhen S, Cani L, Antonioli E, Derudas D, Fazio F, Larocca A, Ronconi S, Cellini C, Falcone AP, Accardi F, Liberati AM, Galieni P, Belotti A, Cafro AM, Ria R, Benevolo G, Vincelli ID, Mannina D, Lotti F, Bruno B, Marasco V, Mazza R, Tosi P, Rivolti E, Boccadoro M, D'Agostino M. Carfilzomib-lenalidomide-dexamethasone versus lenalidomide-dexamethasone in patients with newly diagnosed myeloma ineligible for autologous stem-cell transplantation (EMN20): a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2025 Aug;12(8):e621-e634. doi: 10.1016/S2352-3026(25)00162-0.

    PubMed 40769686

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma and New Diagnosis Tumor, run by Fondazione EMN Italy Onlus at 40 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Minimal residual disease (MRD) (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04096066, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.

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