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Newly Diagnosed Multiple MyelomaPhase 3NCT03742297

Treatment for Elderly Fit Newly Diagnosed Multiple Myeloma Patients Aged Between 65 and 80 Years

A Phase 3 study testing Lenalidomide., Carfilzomib and Bortezomib in people with Newly Diagnosed Multiple Myeloma, run by PETHEMA Foundation at 58 sites in Spain.

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 study is designed as a randomized, controlled, open-label, assessor blind, multicenter superiority trial with three parallel groups, and primary endpoint of immunophenotypic complete responses at 18 months after randomization. Block randomization will be performed with a 1:1:1 allocation ratio. Read more about this study

Who is it for?
Ages 65 to 80 years
Conditions the study is for
Newly Diagnosed Multiple Myeloma
What is being tested?
Lenalidomide., Carfilzomib and Bortezomib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
462 participants
Where
58 sitesSpain
Study dates
22 Oct 2018to Jan 2031
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • Newly diagnosed multiple myeloma patients who require start active treatment according to the IMWG published in 2014
  • Age between 65 and 80 years, both included
  • Fit patient assessed using the comprehensive health status assessment scale (Geriatric Assessment in Hematology, GAH scale, annex 11) (0-94 points GAH scale). Patients with a punctuation ≤42 will be included.
  • Signed informed consent
  • Patients must have measurable disease, defined as follows:
  • For secretory Multiple Myeloma, measurable disease is defined as the presence of quantifiable monoclonal component, ≥ 0.5 g/dL or, the urine light chains excretion is 200 mg/24h or higher.
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  • For poor secretory or non secretory Multiple Myeloma, the level of the affected serum free light chain must be ≥ 10 mg/dL (≥ 100 mg/L, with an abnormal free light-chain ratio)
  • Eastern Cooperative Oncology Group (ECOG) Performance status ≤2
  • Life expectancy more than 3 months
  • Adequate organ functions:
  • Platelet count ≥ 50000/mm3, hemoglobin ≥ 8 g/dl and absolute neutrophil count ≥ 1000/mm3. Lower values are allowed only if they are due to BM infiltration.
  • Aspartate Transaminase (AST) and Alanine Transaminase (ALT) ≤ 2.5 x Upper Limit of Normal.
  • Total bilirubin: ≤2 x Upper Limit of Normal. Serum creatinine ≤ 2 mg/dl. Calcium ≤14mg/dl or corrected serum calcium ≤14mg/dl in patients whose albumin level is out of range Left ventricle ejection fraction ≥ 40%
  • At the discretion of the investigator patient must be able to adhere to all study requirements.
  • Male patients that receives lenalidomide should commit to use of a condom while taking the study drug every time he has sexual contact with a pregnant female of female of childbearing potential even if he has undergone a successful vasectomy; or practice complete abstinence (when this is the preferred and usual lifestyle of the subject); including during periods of dose interruptions and for at least 30 days after treatment completion. Also males under lenalidomide should commit not to donate semen or sperm during study drug treatment, including during periods of dose interruptions, and for at least 90 days after treatment completion.
  • NOTE: Given the age of patients to be included on this Clinical Trial (between 65 and 80 years, both included), there is no possibility of Females of Childbearing Potential (FCBP), therefore the Pregnancy Prevention Program (annex 12) has been modified accordingly.

Who cannot join

  • Patients older than 81 years or younger than 65
  • Patients that do not qualify for fit according to the GAH scale (annex 11) (>43 points GAH scale)
  • Patients who have previously received treatment for multiple myeloma, except for steroid pulses in case of emergency, the administration of bisphosphonates or antialgesic radiotherapy or due to the presence of plasmacytomas requiring some emergency.
  • Men who does not agree to use a condom every time he has sexual contact with a pregnant female or female of childbearing potential, even if he has undergone a successful vasectomy, or men who does not agree to practice complete abstinence (if this is the preferred and usual lifestyle of the subject).
  • Left ventricular ejection fraction <40% Prior history of malignancies, other than multiple myeloma (except for basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or the breast), unless the patient has been free of the disease for ≥ 5 years.
  • Other relevant diseases or adverse clinical conditions:
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  • Myocardial infarction within the 6 months prior to inclusion in the clinical trial A NYHA functional class III-IV, heart failure, uncontrolled angina, uncontrolled ventricular arrhythmia or acute ischemia detected electrocardiographically or conduction system anomalies.
  • History of significant neurological or psychiatric disorders. Active infection. Significant non-neoplastic liver disease (e.g., cirrhosis, active chronic hepatitis).
  • Poorly controlled arterial hypertension. Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form.
  • Human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive or active hepatitis C infection
  • Limitation of the patient's ability to comply with the treatment or follow-up protocol.
  • Uncontrolled endocrine diseases (i.e. diabetes mellitus, hypothyroidism or hyperthyroidism) (i.e. requiring relevant changes in medication within the last month, or hospital admission within the last 3 months).
  • Patients having a peripheral neuropathy ≥ Grade 2 within the 14 days prior to inclusion.
  • Known hypersensibility to any of the study drugs or their excipients.
  • Patients treated with any investigational drug during the previous 30 days.
  • Patients with acute diffuse infiltrative pulmonary disease and/or pericardial disease.
  • Patients who are unable or unwilling to undergo antithrombotic therapy.
  • Patients with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEVI) less than 50%.

Trial locations and contacts

58 sites in 1 country.

58 sites in 1 country

Spain58 sites

  • Complejo Hospitalario Universitario A Coruña

    A Coruña

  • Complejo Hospitalario Universitario de Albacete

    Albacete

  • Hospital General Universitario de Alicante

    Alicante

  • Hospital Universitari Germans Trias i Pujol (ICO Badalona)

    Badalona

  • Hospital Clinic i Provincial de Barcelona

    Barcelona

  • Hospital de la Santa Creu i Sant Pau

    Barcelona

  • Hospital Universitari Vall d´Hebron

    Barcelona

  • ICO L´Hospitalet

    Barcelona

  • Hospital Universitario de Cruces

    Bilbao

  • Complejo Hospitalario de Cáceres

    Cáceres

  • Complejo Hospitalario Regional Reina Sofía

    Córdoba

  • Hospital de Cabueñes

    Gijón

  • Hospital Universitari Dr. Josep Trueta (ICO Girona)

    Girona

  • Hospital de Especialidades de Jerez de la Frontera

    Jerez de la Frontera

  • Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín

    Las Palmas de Gran Canaria

  • Complejo Asistencial Universitario de León

    León

  • Hospital Universitari Arnau de Vilanova de Lleida

    Lleida

  • Hospital San Pedro

    Logroño

  • Complejo Hospitalario Lucus Augusti

    Lugo

  • Hospital 12 de octubre

    Madrid

  • Hospital clínico San Carlos

    Madrid

  • Hospital Ramón y Cajal

    Madrid

  • Hospital Universitario de la Princesa

    Madrid

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid

  • Hospital Universitario Infanta Leonor

    Madrid

  • Hospital Universitario La Paz

    Madrid

  • Hospital Universitario Madrid Sanchinarro

    Madrid

  • HU Gregorio Marañón

    Madrid

  • Hospital Costa del Sol

    Málaga

  • Hospital Virgen de la Victoria

    Málaga

  • Hospital San Joan de Deu (Althaia)

    Manresa

  • Hospital Clínico Universitario Virgen de la Arrixaca

    Murcia

  • Hospital General Universitario Morales Meseguer

    Murcia

  • Hospital General Universitario Santa Lucía

    Murcia

  • Hospital Universitario Central de Asturias

    Oviedo

  • Hospital Son Llatzer

    Palma de Mallorca

  • Hospital Universitario Son Espases

    Palma de Mallorca

  • Clinica Universitaria de Navarra

    Pamplona

  • Complejo Hospitalario de Navarra

    Pamplona

  • Complejo Hospitalario de Pontevedra

    Pontevedra

  • Hospital Universitario de Salamanca

    Salamanca

  • Hospital Universitario de Donostia

    San Sebastián

  • Complejo Hospitalario Universitario Nuestra Señora de la Candelaria

    Santa Cruz de Tenerife

  • Hospital Universitario de Canarias

    Santa Cruz de Tenerife

  • Hospital Universitario Marqués de Valdecilla

    Santander

  • Complejo Hospitalario Universitario de Santiago

    Santiago de Compostela

  • Hospital General de Segovia

    Segovia

  • H. Universitario Virgen de Rocío

    Seville

  • Hospital Nuestra Señona de Valme

    Seville

  • Hospital Universitari Joan XXIII de Tarragona

    Tarragona

  • Complejo Hospitalario de Toledo (Virgen de la Salud)

    Toledo

  • Hospital Clínico Universitario de Valencia

    Valencia

  • Hospital Universitari i Politecnic la Fe

    Valencia

  • Hospital Universitario Dr. Peset Aleixandre

    Valencia

  • Complejo Hospitalario Universitario de Vigo

    Vigo

  • Hospital Txagorritxu

    Vitoria-Gasteiz

  • Hospital Clínico Lozano Blesa

    Zaragoza

  • Hospital Universitario Miguel Servet

    Zaragoza

Other trials in Spain

About this study

Official title: Induction Therapy With Bortezomib-melphalan and Prednisone (VMP) Followed by Lenalidomide and Dexamethasone (Rd) Versus Carfilzomib, Lenalidomide and Dexamethasone (KRd) Plus/Minus Daratumumab, 18 Cycles, Followed by Consolidation and Maintenance Therapy With Lenalidomide and Daratumumab: Phase III, Multicenter, Randomized Trial for Elderly Fit Newly Diagnosed Multiple Myeloma Patients Aged Between 65 and 80 Years

The study is designed as a randomized, controlled, open-label, assessor blind, multicenter superiority trial with three parallel groups, and primary endpoint of immunophenotypic complete responses at 18 months after randomization. Block randomization will be performed with a 1:1:1 allocation ratio.

Patients will be randomized up front to 3 arms. Patients will receive "standard" PETHEMA arm for fit elderly VMP x 9 + Rd x 9 (arm 1, control arm), a KRd regimen (arm 2a) (18 cycles) or a Carfilzomib-lenalidomida-dexametasona regimen combined with DARATUMUMAB (arm 2b) (18 cycles).

Read the detailed description

After 18 cycles, patients not having received daratumumab before (arm 1 and 2a), will receive consolidation with 4 cycles of Lenalidomida-dexamethasone at low dose-DARATUMUMAB.

At this point (after 22 months on treatment for the VMP-Rd and KRd arm and after 18 months of the Carfilzomib-lenalidomida-dexametasona-DARATUMUMAB arm) patients will be stratified according MRD status by flow and in both MRD- and MRD+ groups, patients will be randomized with a 1:1 allocation ratio to:

  1. no further treatment or
  2. continuous treatment with DARATUMUMAB-R (daratumumab plus lenalidomide up to 2 years and then lenalidomide continuous until progression).

Patients on no maintenance that show biological relapse will be rechallenged with DARATUMUMAB-R.

The translational part will be very robust with dysplasia monitoring (especially relevant for the Bortezomib-melfalán-prednisona + Lenalidomida-dexamethasone at low dose arm), clonal evolution/resistance follow up and immune reconstitution longitudinal follow up alongside with MRD status (at diagnosis, 9 months, 18 months, 22 months and treatment discontinuation).

The trial is designed as a two-stage study (induction, followed by consolidation and maintenance). The first stage is confirmatory and addresses the primary efficacy objective. The second stage is exploratory and addresses the secondary efficacy and safety objectives.

In the first stage, investigators will compare an optimized standard induction Bortezomib, talidomida and prednisone followed by Rd (18 cycles) versus KRd, that will be tested in this trial with or without daratumumab x 18 cycles. The main objective in this stage will be to compare the immunophenotypic complete response rate assessed by next generation flow at the end of induction.

The second stage is exploratory and includes the consolidation and maintenance phases. In this second stage, the main objectives are:

  1. To compare the above mentioned induction strategies in terms of PFS at the end of the different treatment phases (induction, consolidation and maintenance).
  2. To investigate the capacity of consolidation with daratumumab-lenalidomide to reduce MRD levels in patients treated in the control arm as well as those that received KRd without daratumumab. In addition we will explore if this short consolidation can abrogate the potential benefit of a prolonged induction with KRd+daratumumab
  3. To explore the value of maintenance therapy according to MRD status (positive or negative) to prolong PFS (after a second randomization to receive or not maintenance therapy with lenalidomide and daratumumab) In order to prevent a potential treatment deficiency for patients randomized to "no-maintenance" in both MRD+ and MRD- subgroups, they will be offered to be re-challenged with lenalidomide-daratumumab as soon as they have a biological progression and have been censored for PFS. Moreover, if 30% of the patients randomized to "no-maintenance" relapse or progress during the first year, the protocol will be amended so that all patients receive maintenance therapy.

Investigators consider that the here proposed multidrug sequential "intensive" approach designed to obtain the best possible and most durable response, assessed through the kinetics of MRD clearance, may have an impact in establishing future clinical practice in fit elderly patients. Moreover, in addition to the MRD analysis (based on next generation flow (NGF), NGS and CT-PET) comprehensive biological investigations, including immunoprofile, clonal selection, analysis of dysplastic features and circulating tumor cells, are planned in order to better understand the relationship between patients outcome and myeloma biology.

The overall treatment plan has been designed for NDMM patients not candidates to SCT strategies but fit enough to tolerate a relatively intensive therapeutic strategy. According to the International Myeloma Working Group guidelines as well as the results obtained in our GEM2010 trial for elderly patients, we have decided to restrict this trial to fit elderly patients aged between 65 and 80 years because in our experience patients older than 80 years usually intensive treatments are poorly tolerated [1].

Investigators will evaluate the frailty using a comprehensive health status assessment scale (Geriatric Assessment in Hematology, GAH scale, annex 11), already validated in patients with hematological diseases and preliminary results in multiple myeloma patients

What participants receive

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

Study groups in NCT03742297
Study groupRoleWhat they receive
VMP x 9 + Lenalidomida-dexamethasone x 9Active comparatorBortezomib-melfalán-prednisone. Melfalán: 9mg/m2D1-4. Prednisone: 60mg/m2D1-4. Bortezomib: 1.3mg/m2 One 6 week cycleD1, 4, 8, 11, 22, 25, 29 and 32; followed by eight4-week cycleD1, 8, 15 and 22 Lenalidomida-dexametasona at low dose
Receives: Drug: Lenalidomide.; Drug: Bortezomib; Drug: Dexamethasone; Drug: Prednisone; Drug: Melphalan
Carfilzomib-lenalidomida-dexamethasone regimenExperimentalcarfilzomib: 1 st cycle: 20mg/m2 day 1 and 36 mg/m2 days 2, 8, 9 \& 15, 16. 2nd cycle: 36 mg/m2 days 1, 2, 8, 9 \& 15, 16. Cycles 3-18: 56 mg/m2 days 1, 8 \& 15.Lenalidomida: 25 mg, d1-21 Dexamethasone : 40 mg, d1, 8, 15, 2218 28-day cycle
Receives: Drug: Lenalidomide.; Drug: Carfilzomib; Drug: Dexamethasone
Carfilzomib-lenalidomida-dexamethason with daratumumabExperimentalCarfilzomib: 1 st cycle: 20mg/m2 day 1 and 36 mg/m2 days 2, 8, 9 \& 15, 16. 2nd cycle: 36 mg/m2 days 1, 2, 8, 9 \& 15, 16. Cycles 3-18: 56 mg/m2 days 1, 8 \& 15. Lenalidomida: 25 mg, d1-21 Dexamethasone: 40 mg, d1, 8, 15, 22. Daratumumab 1800mg SC Days 1, 8, 15, 22 of cycles 1-2; Days 1 and 15 of cycles 3 and 4; Day 1 of cycles 5 to 18
Receives: Drug: Lenalidomide.; Drug: Carfilzomib; Drug: Daratumumab; Drug: Dexamethasone

What is being measured

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

  1. Efficacy in terms of numbers of compleat responses

    Rate of immunophenotypic complete responses at 18 months, of the standard treatment in Spain for newly diagnosed multiple myeloma patients not candidates to stem cell transplantation,

    Measured: 18 months

Timeline

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

  1. First posted15 Nov 2018
  2. Study start22 Oct 2018
  3. Primary completionJul 2023 (estimated)
  4. Study completionJan 2031 (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
462 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03742297
Sponsor's protocol ID
GEM2017FIT
Status last verified
Sep 2022
First submitted
13 Nov 2018
Last updated
14 Sep 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Mateos MV, Paiva B, Cedena MT, Puig N, Sureda-Balari AM, de la Calle VG, Oriol A, Ocio EM, Rosinol L, Montes YG, Bargay J, Garcia MEG, Lakhwani S, Payer AR, Suarez-Cabrera A, Blanchard MJ, Garzon S, Montero FC, Cabanas V, de Oteyza JP, Gironella M, Martinez-Lopez J, Casasus AIT, Delgado-Beltran MP, Prieto E, Lahuerta JJ, Blade J, San-Miguel J. Induction therapy with bortezomib, melphalan, and prednisone followed by lenalidomide and dexamethasone versus carfilzomib, lenalidomide, and dexamethasone with or without daratumumab in older, fit patients with newly diagnosed multiple myeloma (GEM-2017FIT): a phase 3, open-label, multicentre, randomised clinical trial. Lancet Haematol. 2025 Aug;12(8):e588-e598. doi: 10.1016/S2352-3026(25)00143-7.

    PubMed 40769684

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Lenalidomide., Carfilzomib and Bortezomib in people with Newly Diagnosed Multiple Myeloma, run by PETHEMA Foundation at 58 sites in Spain.

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 16 inclusion and 18 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 14 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in Spain. 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?

Efficacy in terms of numbers of compleat responses (time frame: 18 months). 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 NCT03742297, 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 14 Sep 2022.

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