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Multiple MyelomaPhase 3NCT02406144

Trial Studying Maintenance Treatment With Lenalidomide and Dexamethasone Versus Lenalidomide, Dexamethasone and MLN9708 After Autologous Hematopoietic Stem Cell Transplantation in Patients With Newly-diagnosed Symptomatic Multiple Myeloma

A Phase 3 study testing MLN9708, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by PETHEMA Foundation at 74 sites in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This protocol is a randomized, open-label, national, multicenter trial studying maintenance treatment with lenalidomide and dexamethasone versus lenalidomide, dexamethasone and MLN9708 after autologous hematopoietic stem cell transplantation in patients with newly-diagnosed symptomatic multiple myeloma. Read more about this study

Who is it for?
Ages 18 to 67 years
Conditions the study is for
Multiple Myeloma
What is being tested?
MLN9708, Lenalidomide and Dexamethasone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
316 participants
Where
74 sitesSpain
Study dates
Nov 2014to Nov 2017
Phase
Phase 3
Are there results?
None posted in the registry

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 18 to 67 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The patient must, in the opinion of the investigator, be capable of complying with all requirements of the trial.
  • Have signed the informed consent form
  • Be between 18 and 67 years of age
  • Have an ECOG Performance Status <= 2 (or 3 if the ECOG is due to myeloma, e.g. pathological fracture)
  • Multiple myeloma patient who was included in the GEM2012MENOS65 trial, and who is found to have, at a minimum, minimal response after consolidation
  • Life expectancy > 3 months
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  • The patient must have the following laboratory values in the 21 days prior to initiation of treatment (day 1, cycle 1):
  • Platelet count ≥ 100 x 109/L and absolute neutrophil count of ≥ 1.0 x 109/L. - Platelet transfusions to help patients meet eligibility criteria are not allowed.
  • Corrected serum calcium < 14 mg/dL.
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x the upper limit of normal (ULN)
  • Total bilirubin within normal range
  • Calculated creatinine clearance > 30 mL/min
  • Female patients who:
  • Are postmenopausal for at least 1 year before the screening visit, OR
  • Are surgically sterile, OR
  • If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
  • Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR 30 Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

Who cannot join

  • Patients not included in clinical trial GEM2012MENOS65
  • Patients included in GEM2012MENOS65 who are not found to have a least minimal response after consolidation
  • Patients included in GEM2012MENOS65 who were discontinued prematurely due to toxicity or disease progression
  • Female patients who are lactating or have a positive serum pregnancy test during the screening period.
  • Central nervous system involvement
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
Show all 15Show fewer
  • Systemic treatment, within 14 days before the first dose of MLN9708, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing.
  • Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  • Peripheral neuropathy ≥ grade 2 in the 21 days prior to inclusion.
  • Known hypersensitivity to lenalidomide or to MLN9708, their analogues, or excipients in the various formulations of any agent.
  • Patients who have had a myocardial infarction in the six months prior to inclusion in the clinical trial, or who are class III or IV according to the New York Heart Association (NYHA), heart failure unstable angina, uncontrolled ventricular arrhythmias or acute ischemia detected by electrocardiogram, or conduction disorders.
  • Patients who are currently participating in another clinical trial or receiving any other investigational product.
  • Seropositive for HVB, HVC or HIV.

Trial locations and contacts

74 sites in 1 country.

74 sites in 1 country

Spain74 sites

  • Complejo Hospitalario Universitario de Santiago

    A Coruña

  • Hospital Txagorritxu

    Alava

  • Hospital General de Albacete

    Albacete

  • Hospital Del Vinalopo

    Alicante

  • Hospital General Universitario de Alicante

    Alicante

  • Hospital de Cabueñes

    Asturias

  • Hospital Universitario Central de Asturias

    Asturias

  • Hospital Clinic

    Barcelona, 08036

  • H.Universitari Germans Trias I Pujol de Badalona

    Barcelona

  • Hospital de La Santa Creu I Sant Pau

    Barcelona

  • Hospital de Sabadell (Parc Taulí)

    Barcelona

  • Hospital de Sant Joan de Déu

    Barcelona

  • Hospital Del Mar

    Barcelona

  • Hospital Universitari Mútua de Terrasa

    Barcelona

  • Hospital Vall D'Hebron

    Barcelona

  • Ico L'Hospitalet

    Barcelona

  • Hospital Universitario de Burgos

    Burgos

  • Complejo Hospitalario de Cáceres

    Cáceres

  • Hospital de Especialidades de Jerez de La Frontera

    Cadiz

  • Hospital Universitario Marqués de Valdecilla

    Cantabria

  • Hospital General de Castellón

    Castelló

  • Hospital General de Ciudad Real

    Ciudad Real

  • Hospital Universitari Dr. Josep Trueta de Girona

    Girona

  • Hospital de Gran Canaria Doctor Negrín

    GRAN Canaria

  • Hospital Universitario Virgen de Las Nieves

    Granada

  • Hospital Universitario Guadalajara

    Guadalajara

  • Hospital Universitario Donostia

    Guipúzcoa

  • Hospital Son Llatzer

    Illes Balears

  • Hospital Universitari Son Espases

    Illes Balears

  • Hospital San Pedro

    La Rioja

  • Hospital de León

    León

  • Hospital Universitari Arnau de Vilanova de Lleida

    Lleida

  • Centro Oncológico Md Anderson International España

    Madrid

  • Fundación Jiménez Díaz-Ute

    Madrid

  • Hm Universitario San Chinarro

    Madrid

  • Hospital Clínico San Carlos

    Madrid

  • Hospital de Fuenlabrada

    Madrid

  • Hospital Del Tajo

    Madrid

  • Hospital General Universitario Gregorio Marañón

    Madrid

  • Hospital Infanta Leonor

    Madrid

  • Hospital Infanta Sofía

    Madrid

  • Hospital Ramón Y Cajal

    Madrid

  • Hospital Severo Ochoa

    Madrid

  • Hospital Universitario 12 de Octubre

    Madrid

  • Hospital Universitario de La Princesa

    Madrid

  • Hospital Universitario Fundación Alcorcón

    Madrid

  • Hospital Universitario Infanta Cristina

    Madrid

  • Hospital Universitario La Paz

    Madrid

  • Hospital Universitario Puerta de Hierro Majadahonda

    Madrid

  • Complejo Hospital Costa Del Sol (Ivcs)

    Málaga

  • Hospital General Universitario Santa Lucia

    Murcia

  • Hospital J.M. Morales Meseguer

    Murcia

  • Hospital Universitario Virgen de La Arrixaca

    Murcia

  • Clinica Universidad de Navarra

    Navarra

  • Complejo Hospitalario de Navarra

    Navarra

  • Complejo Hospitalario de Ourense

    Ourense

  • Complejo Hospitalario de Pontevedra

    Pontevedra

  • Hospital Universitario de Salamanca

    Salamanca

  • Hospital Universitario de Canarias

    Santa Cruz de Tenerife

  • Hospital General de Segovia

    Segovia

  • Hospital Nuestra Señora de Valme

    Seville

  • Hospital Virgen del Rocío

    Seville

  • Hospital Santa Bárbara

    Soria

  • Hospital Universitari Joan Xxiii de Tarragona

    Tarragona

  • Complejo Hospitalario de Toledo

    Toledo

  • Hospital Nuestra Señora Del Prado

    Toledo

  • Hospital Clínico Universitario Valencia

    Valencia

  • Hospital Universitario Dr. Peset

    Valencia

  • Hospital Universitario La Fe

    Valencia

  • HOSPITAL CLíNICO UNIVERSITARIO DE VALLADOLID

    Valladolid

  • Hospital Universitario Del Rio Hortega

    Valladolid

  • Hospital de Cruces

    Vizcaya

  • Hospital Clínico Universitario Lozano Blesa

    Zaragoza

  • Hospital Universitario Miguel Servet

    Zaragoza

Other trials in Spain

About this study

This protocol is a randomized, open-label, national, multicenter trial studying maintenance treatment with lenalidomide and dexamethasone versus lenalidomide, dexamethasone and MLN9708 after autologous hematopoietic stem cell transplantation in patients with newly-diagnosed symptomatic multiple myeloma.

A total of 316 patients, from the study GEM2012MENOS65, will be enrolled in the study.

Read more

The pre-treatment period includes the screening visit in which participants provide informed consent in writing in order to take part in the study. The patient is then assessed to determine his/her eligibility. The selection process will begin 21 days before the first dose of medication is administered (days -21 to 0). All procedures during the pre-treatment period will be carried out after completion of the two cycles of post-transplant consolidation with VRD which coincide with the end-of-study visit of clinical trial GEM2012MENOS65.

During the treatment period, eligible patients will be included in the study and receive maintenance treatment with lenalidomide/dexamethasone versus lenalidomide/dexamethasone/MLN9708. Each cycle will last 28 days. Treatment arm A will consist of oral administration of 15 mg/day of oral lenalidomide on days 1-21, and 20 mg/day of dexamethasone administered orally on days 1-4 and 9-12 for a period of two years. Arm B of the maintenance treatment will be the same as arm A, with the addition of MLN9708 during the two year maintenance period, at a dose of 4 mg/day on days 1, 8 and 15 of the cycle.

At two years, patients with negative MRD will finish maintenance treatment. Patients with positive MRD will continue treatment with lenalidomide/dexamethasone until they have completed five years of maintenance treatment. In this case, 20 mg/day of dexamethasone will only be administered on days 1-4 of the cycle. The dose of lenalidomide will not be adjusted. (unless necessary to treat adverse events)

Once this phase of active treatment is complete, patients will begin the long-term follow-up phase, during which they will be visited every three months to evaluate progression and survival.

Read the detailed description

The primary trial objectives are:

  • Impact on progression-free survival (PFS) when adding MLN9708 to post-transplant maintenance treatment with lenalidomide/dexamethasone in patients with multiple myeloma.

The secondary trial objectives are:

  • Evaluate development and clinical significance of minimal residual disease (MRD) from the time maintenance treatment is initiated, yearly over five years.
  • Overall survival (OS).
  • Evaluate the safety and tolerability of the maintenance treatment.
Being tested
MLN9708, Lenalidomide, Dexamethasone
Keywords
Multiple Myeloma
Medical subject headings
Multiple Myeloma

What participants receive

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

Study groups in NCT02406144
Study groupRoleWhat they receive
LenalidomideActive comparatorOral administration of 15 mg/day of oral lenalidomide on days 1-21, and 20 mg/day of dexamethasone administered orally on days 1-4 and 9-12 for a period of two years
Receives: Drug: Lenalidomide; Drug: Dexamethasone
MLN9708 plus LenalidomideExperimentalMLN9708 during the two year maintenance period, at a dose of 4 mg/day on days 1, 8 and 15 of the cycle.
Receives: Drug: MLN9708; Drug: Lenalidomide; Drug: Dexamethasone

What is being measured

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

  1. Progression-free survival

    Months to progression disease

    Measured: 5 years

Secondary outcomes (2)

  1. Minimal Residual Disease (MRD)

    Number of patient with MRD and evaluation of its clinical significance

    Measured: 5 years

  2. Overall survival

    Months of survival

    Measured: 6 years

Timeline

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

  1. First posted2 Apr 2015 (estimated)
  2. Study startNov 2014
  3. Primary completionSep 2017
  4. Study completionNov 2017

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
316 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02406144
Sponsor's protocol ID
GEM2014MAIN
Status last verified
Nov 2017
First submitted
25 Mar 2015
Last updated
30 Nov 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Puig N, Agullo C, Contreras T, Cedena MT, Martinez-Lopez J, Oriol A, Blanchard MJ, Rios R, Inigo MB, Sureda A, Lakhwani S, de la Rubia J, Gonzalez-Calle V, Cabanas V, Palomera L, Moraleda JM, Bargay J, Castro S, Rosinol L, Blade J, San-Miguel JF, Lahuerta JJ, Paiva B, Mateos MV. Measurable residual disease by mass spectrometry and next-generation flow to assess treatment response in myeloma. Blood. 2024 Dec 5;144(23):2432-2438. doi: 10.1182/blood.2024024995.

    PubMed 39293025

  • Guerrero C, Puig N, Cedena MT, Calasanz MJ, Gutierrez NC, Fernandez M, Oriol A, Rios-Tamayo R, Hernandez MT, Martinez-Martinez R, Bargay J, de Arriba F, Palomera L, Gonzalez-Rodriguez AP, Gonzalez Perez MS, Orfao A, Mateos MV, Martinez-Lopez J, Rosinol L, Blade J, Lahuerta JJ, San-Miguel JF, Paiva B. Predictors of unsustained measurable residual disease negativity in transplant-eligible patients with multiple myeloma. Blood. 2024 Feb 15;143(7):597-603. doi: 10.1182/blood.2023022083.

    PubMed 38048552

  • Lakhwani S, Rosinol L, Puig N, Pico-Picos MA, Medina-Gonzalez L, Martinez-Lopez J, Paiva B, Cedena MT, Oriol A, Rios-Tamayo R, Blanchard MJ, Jarque I, Bargay J, Moraleda JM, Carrillo-Cruz E, Sureda A, Krsnik I, Gonzalez E, Casado LF, Marti JM, Encinas C, De Arriba F, Palomera L, Sampol A, Gonzalez-Montes Y, Motllo C, De La Cruz J, Alonso R, Mateos MV, Blade J, Lahuerta JJ, San-Miguel J, Hernandez MT. Recovery of uninvolved heavy/light chain pair immunoparesis in newly diagnosed transplant-eligible myeloma patients complements the prognostic value of minimal residual disease detection. Haematologica. 2024 Jun 1;109(6):1909-1917. doi: 10.3324/haematol.2023.284154.

    PubMed 38031761

  • Rosinol L, Oriol A, Rios R, Blanchard MJ, Jarque I, Bargay J, Hernandez MT, Cabanas V, Carrillo-Cruz E, Sureda A, Martinez-Lopez J, Krsnik I, Gonzalez ME, Casado LF, Marti JM, Encinas C, de Arriba F, Palomera L, Sampol A, Gonzalez-Montes Y, Cabezudo E, Paiva B, Puig N, Cedena MT, de la Cruz J, Mateos MV, San Miguel J, Lahuerta JJ, Blade J. Lenalidomide and dexamethasone maintenance with or without ixazomib, tailored by residual disease status in myeloma. Blood. 2023 Nov 2;142(18):1518-1528. doi: 10.1182/blood.2022019531.

    PubMed 37506339

  • Botta C, Maia C, Garces JJ, Termini R, Perez C, Manrique I, Burgos L, Zabaleta A, Alignani D, Sarvide S, Merino J, Puig N, Cedena MT, Rossi M, Tassone P, Gentile M, Correale P, Borrello I, Terpos E, Jelinek T, Paiva A, Roccaro A, Goldschmidt H, Avet-Loiseau H, Rosinol L, Mateos MV, Martinez-Lopez J, Lahuerta JJ, Blade J, San-Miguel JF, Paiva B. FlowCT for the analysis of large immunophenotypic data sets and biomarker discovery in cancer immunology. Blood Adv. 2022 Jan 25;6(2):690-703. doi: 10.1182/bloodadvances.2021005198.

    PubMed 34587246

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing MLN9708, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by PETHEMA Foundation at 74 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 21 inclusion and 15 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: finished, as of the sponsor's last update on 30 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 74 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Progression-free survival (time frame: 5 years). 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 NCT02406144, which also lists 5 linked publications.

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 30 Nov 2017.

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