AzTrials
AzTrials

Newly Diagnosed Multiple MyelomaPhase 3GEM21menos65NCT05558319

NDMM Patients Candidates for ASCT Comparing Extended VRD Plus vs. Isa-VRD vs. Isa-V-Iberdomide

A Phase 3 study testing Bortezomib, Isatuximab and Iberdomide in people with Newly Diagnosed Multiple Myeloma, run by PETHEMA Foundation at 68 sites in Spain.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a Phase III open-label, 3-arm, parallel, randomized, controlled trial. The allocation ratio 1:1:1 and outcome assessment are blind to group allocation. Patients will be randomized from 3 arms. Patients will receive VRD extended + ASCT plus ERI or Isatuximab-VRD + ASCT or Isatuximab-VID + ASCT. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Newly Diagnosed Multiple Myeloma
What is being tested?
Bortezomib, Isatuximab and Iberdomide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
480 participants
Where
68 sitesSpain
Study dates
10 Nov 2022to Apr 2029
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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
  • Patient must be able to understand the study procedures.
  • Patient has given voluntary written informed consent before performance of any studyrelated procedure non part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
  • Newly diagnosed multiple myeloma patient who requires start active treatment according to the 2014 IMWG criteria, namely clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events: evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: Hypercalcaemia, Anaemia, Renal Insufficiency, or Bone lesions (one or more osteolytic lesions on skeletal radiography, CT, or PET-CT), and any one or more of the following biomarkers: clonal BMPC% ≥60%, i/u free light ratio ≥100 or > 1 focal lesions on MRI or PET/CT) [Lancet Oncol. 2014;15(12): e538-e548].
  • Patient must have a measurable secretory disease defined as either serum monoclonal protein of ≥ 0,5 g/dl or urine monoclonal (light chain) protein ≥ 200 mg/24 h. For patients whose disease is only measurable by serum FLC, the involved FLC should be ≥ 10mg/dL (100 mg/L), with an abnormal serum FLC ratio.
  • Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
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  • Patient must be ≤ 65 years of age.
  • Patient must have adequate organ function, defined as follows:
  • Absolute neutrophil count (ANC) ≥1.0 X 109/L without G-CSF use in the prior 7 days
  • Hemoglobin ≥8.0 g/dL (prior red blood cell (RBC) transfusion or recombinant human erythropoietin use is permitted)
  • Platelets ≥ 75 x 109/L in participants in whom <50% of bone marrow nucleated cells are plasma cells and ≥ 50×109/L in participants in whom ≥50% of bone marrow nucleated cells are plasma cells (without transfusion support or thrombopoietin receptor agonist within 7 days before the laboratory test).
  • Calcium Corrected serum calcium ≤13.5 mg/dL (≤3.4 mmol/L); or free ionized calcium ≤6.5 mg/dL (≤1.6 mmol/L).
  • Total bilirubin ≤2 X ULN
  • ALT ≤2.5 X ULN
  • AST ≤2.5 X ULN
  • Renal: eGFRa: ≥40 mL/min/ 1.73 m2
  • Cardiac: LVEF (echo) ≥ 50%
  • Female patient: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female patient is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a woman of childbearing potential (WOCBP), i.e., fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy OR
  • Is a WOCBP and
  • She understands the potential teratogenic risk to the unborn child
  • She understands the need for effective contraception as stated in the protocol, without interruption, 28 days before starting study treatment, throughout the entire duration of study treatment, during dose interruptions and for at least 28 days after the last dose of study treatment.
  • She understands and agrees to inform the Investigator if a change or stop of method of contraception is needed.
  • She must be capable of complying with effective contraceptive measures.
  • She is informed and understands the potential consequences of pregnancy and the need to notify her study doctor immediately if there is a risk of pregnancy.
  • She understands the need to commence study treatment as soon as it is dispensed following a negative pregnancy test.
  • She understands and accepts the need to undergo pregnancy testing based on the frequency outlined in this plan and in the Informed Consent.
  • She acknowledges she understands the hazards iberdomide or lenalidomide can cause to an unborn fetus and the necessary precautions associated with the use of study drugs.
  • The Investigator must ensure that a WOCBP: i) Complies with the conditions of the pregnancy prevention plan, including confirmation that she has an adequate level of understanding. ii) Acknowledges the aforementioned requirements.
  • A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study drug.
  • Nonchildbearing potential is defined as follows (by other than medical reasons):
  • Has not achieved menarche at some point.
  • Has undergone a hysterectomy or bilateral oophorectomy.
  • Has been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months).
  • Male patient: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Male patient is eligible to participate if he agrees to the following from the time of first dose of study until 6 months after the last dose of iberdomide or lenalidomide to allow for clearance of any altered sperm:
  • Understand the potential teratogenic risk if engaged in sexual activity with a pregnant female or a WOCBP.
  • Understand the need for the use of a condom even if he has had a vasectomy, if engaged in sexual activity with a pregnant female or a FCBP
  • Understand the potential teratogenic risk, so the subject should not donate semen or sperm.. Understand that the effects on fertility are currently unknown, therefore all family planning options and/or alternatives should be thoroughly discussed with the study doctor prior to receiving iberdomide.
  • All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 5.0 must be ≤ Grade 1 at the time of enrolment except for alopecia.

Who cannot join

  • Patient has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), plasma cell leukemia or active POEMS syndrome at the time of screening.
  • Patient has had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma.
  • 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.
  • Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study; subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and/or lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment.
  • Pregnant or breastfeeding females.
  • Men and women of reproductive potential who are not using effective contraceptive methods (double barrier method, intrauterine device, oral contraception).
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  • Patient is simultaneously enrolled in other interventional clinical trial.
  • Patient has used an investigational drug within 28 days or five half-lives, whichever is longer, preceding the first dose of study drug.
  • Patient must not have received prior radiotherapy (except localized palliative radiotherapy for pain, palliation or fracture) within 2 weeks of start of study therapy. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
  • Major surgery (except kyphoplasty) ≤ 4 weeks prior to initiating protocol therapy.
  • Patient has peripheral neuropathy or neuropathic pain grade 1 with pain or ≥2, as defined by the National Cancer Institute Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
  • Patient evidence of cardiovascular risk including any of the following:
  • Myocardial infarction within 6 months before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV).
  • Uncontrolled cardiac arrhythmia.
  • Screening 12-lead ECG showing a baseline interval QTcF> 470 msec (exception: subjects with pacemaker).
  • Patients with uncontrolled hypertension.
  • Patients who have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria.
  • Presence of active renal condition (infection, requirement for dialysis or any other condition that could affect patient's safety). Participants with isolated proteinuria resulting from MM are eligible, provided they fulfil inclusion criteria.
  • Evidence of active mucosal or internal bleeding.
  • Any serious medical condition or psychiatric illness that would interfere in understanding of the informed consent form.
  • 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).
  • Patient with acute diffuse infiltrative pulmonary disease and/or pericardial disease.
  • Patient with severe chronic obstructive pulmonary disease (COPD) or asthma with forced expiratory volume in the first minute (FEV1) less than 50%.
  • History of interstitial lung disease or ongoing interstitial lung disease.
  • Subject has gastrointestinal disease that may significantly alter the absorption of iberdomide and/or other oral study treatment.
  • Patient has an active infection requiring systemic antibiotic, antiviral, or antifungal treatment at the time of starting treatment.
  • Patient has known HIV infection.
  • Patient has positive hepatitis B surface antigen (HBsAg), or hepatitis B core antibody (HBcAb) at screening or within 3 months prior to first dose of study treatment.
  • Patient has positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment. Note: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody test are not required.
  • Patient require concurrent administration of a strong inhibitor or inducer of cytochrome P450 (CYP3A4/5) (including within 14 days of initiating study treatment).
  • Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to iberdomide or drugs chemically related to iberdomide.
  • Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to isatuximab or drugs chemically related to isatuximab, hypersensitivity reactions, or idiosyncratic reactions to other molecular antibodies.
  • Patient has a known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to lenalidomide or dexamethasone or drugs chemically related to lenalidomide or dexamethasone.

Trial locations and contacts

68 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Carmen López-Carrero contact

0034 699 835 437

carmen@fundacionpethema.es

Roberto Maldonado contact

0034 683 15 66 87

roberto.maldonado@fundacionpethema.es

68 sites in 1 country

Spain68 sites, 65 recruiting

  • Hospital General Universitario de Albacete

    Albacete

    Irene Gómez Catalán, irenevonu12@gmail.com

    Irene Gómez Catalán

    Recruiting

  • Hospital Principe de Asturias

    Alcalá de Henares, Madrid

    Julio García Suárez, jgsuarez@salud.madrid.org

    Julio García Suárez, Dr

    Recruiting

  • Hospital Germans Trias i Pujol (ICO BADALONA)

    Badalona

    Albert Oriol Rocafiguera, aoriol@iconcologia.net

    Albert Oriol Rocafiguera

    Recruiting

  • Hospital Clinic i Provincial de Barcelona

    Barcelona

    Laura Rosiñol, Dr, 93 2275400, LROSINOL@clinic.cat

    Laura Rosiñol

    Recruiting

  • Hospital de la Santa Creu i Sant Pau

    Barcelona

    Miguel Granell Gorrochategui, Dr, 93 5565647, MGranell@santpau.cat

    Miguel Granell Gorrochategui

    Recruiting

  • Hospital Universitari Vall d´Hebron

    Barcelona

    Mercedes Gironella Mesa, Dr, 93 2746100, mgironel@gmail.com; mgironel@vhebron.net

    Mercedes Gironella Mesa

    Recruiting

  • ICO L´Hospitalet

    Barcelona

    Anna Sureda Balari, Dr, 93 2607750, asureda@iconcologia.net

    Anna Sureda Balari

    Recruiting

  • Hospital Universitario de Cruces

    Bilbao

    Elena Amutio Díez, Dr, 946 006320, mariaelena.amutiodiez@osakidetza.net

    Elena Amutio Díez

    Recruiting

  • Hospital Universitario de Burgos

    Burgos, 09006

    Francisco Javier Díaz Gálvez, fcdiaz@saludcastillayleon.es

    Francisco Javier Díaz Gálvez

    Recruiting

  • Complejo Hospitalario de Cáceres

    Cáceres

    Ignacio Casas Avilés, Dr, 927 256200, ignacio.casas@salud-juntaex.es

    Ignacio Casas Avilés

    Recruiting

  • Hospital Universitario de Cabueñes

    Gijón

    María Esther González García, + 34 985 18 50 00, esthergongar@yahoo.es

    María Esther González García

    Recruiting

  • Hospital Universitari Dr. Josep Trueta (ICO Girona)

    Girona

    Yolanda González Montes, Dr, 972 225833, ygonzalez@iconcologia.net

    Yolanda González Montes

    Recruiting

  • Hospital Universitario Virgen de las Nieves

    Granada

    María Esther Clavero Sánchez, eclaverosa@hotmail.com

    María Esther Clavero Sánchez

    Recruiting

  • Hospital Universitario de Guadalajara

    Guadalajara

    Dunia de Miguel Llorente, duniamll@hotmail.com

    Dunia de Miguel Llorente

    Recruiting

  • H.Universitario de Jerez de la Frontera

    Jerez de la Frontera

    Sebastián Garzón López, Dr, sebastianf.garzon.sspa@juntadeandalucia.es

    Sebastian Garzón López

    Recruiting

  • Complejo Asistencial Universitario de León

    León

    Fernando Escalante Barrigón, Dr, 987 237400, fescalanteb@yahoo.es

    Fernando Escalante Barrigón

    Recruiting

  • Hospital Arnau de Vilanova (Lleida)

    Lleida

    Antoni Garcia Guiñon, agarciag.lleida.ics@gencat.cat

    Antoni Garcia Guiñon

    Recruiting

  • Hospital San Pedro

    Logroño

    María José Nájera Irazu, Dr, 941 298000, mjnajera@riojasalud.es

    María José Nájera Irazu

    Recruiting

  • Complejo Hospitalario Lucus Augusti

    Lugo

    Esperanza Lavilla Rubia, Dr, 982 296000, Esperanza.Lavilla.Rubira@sergas.es

    Esperanza Lavilla Rubia

    Recruiting

  • Fundación Jiménez Díaz-Ute

    Madrid

    Elena Prieto Pareja, Dr, eprieto@fjd.es

    Elena Prieto Pareja

    Recruiting

  • Hospital General Universitario Gregorio Marañón

    Madrid

    Cristina Encinas Rodríguez, crisenro@hotmail.com

    Cristina Encinas Rodríguez

    Recruiting

  • Hospital HLA Universitario Moncloa

    Madrid

    María Concepción Alaez Usón, concha.alaez@gmail.com

    María Concepción Alaez Usón

    Recruiting

  • Hospital Universitario 12 de octubre

    Madrid

    Joaquín Martínez López, Dr, jmarti01@med.ucm.es

    Joaquín Martínez López

    Recruiting

  • Hospital Universitario Clínico San Carlos

    Madrid

    Celina María Benavente Cuesta, celinamaria.benavente@salud.madrid.org

    Celina María Benavente Cuesta

    Recruiting

  • Hospital Universitario de Fuenlabrada

    Madrid

    Pilar Bravo Barahona, Dr, 91 6006379, pilar.bravo@salud.madrid.org; pilarbravob@gmail.com

    Pilar Bravo Barahona

    Recruiting

  • Hospital Universitario de la Princesa

    Madrid

    Adrián Alegre Amor, Dr, adrian.alegre@telefonica.net; aalegre.hlpr@salud.madrid.org

    Alegre Adrián Amor, Dr

    Recruiting

  • Hospital Universitario Fundación Alcorcón

    Madrid

    Completed

  • Hospital Universitario HM Sanchinarro

    Madrid

    Jaime Pérez de Oteyza, Dr, + 34 902 08 98 00, jperezoteyza@hmhospitales.com

    Jaime Pérez de Oteyza

    Recruiting

  • Hospital Universitario Infanta Leonor

    Madrid

    Jose Ángel Hernández Rivas, jahernandezr@salud.madrid.org; jahr_jahr2006@yahoo.es

    Jose Ángel Hernández Rivas

    Recruiting

  • Hospital Universitario La Paz

    Madrid

    Ana López de la Guía, lopguia@gmail.com

    Ana López de la Guía

    Recruiting

  • Hospital Universitario La Zarzuela

    Madrid

    Daniel García Belmonte, dgarciabe@sanitas.es

    Daniel García Belmonte

    Recruiting

  • Hospital Universitario Puerta del Hierro

    Madrid

    Rafael Ríos Tamayo, rriost33@gmail.com

    Rafael Ríos Tamayo

    Recruiting

  • Hospital Universitario Ramón y Cajal

    Madrid

    María Jesús Blanchard Rodríguez, Dr, + 34 913 36 80 00, mjesusblanchard@yahoo.es

    María Jesús Blanchard Rodríguez

    Recruiting

  • Hospital Costa del Sol

    Málaga

    María Casanova Espinosa, Dr, 951 976798, mariacasanova@yahoo.com

    María Casanova Espinosa

    Recruiting

  • Hospital Regional de Málaga

    Málaga

    María Magdalena Alcalá Peña, kikistrata@hotmail.com

    María Magdalena Alcalá Peña

    Recruiting

  • Hospital U Niversitario Virgen de La Victoria

    Málaga

    Ricarda García Sánchez, Dr, + 34 951 03 20 00, ricarda_g@yahoo.es

    Ricarda García Sánchez

    Recruiting

  • Hospital Universitario Rey Juan Carlos

    Móstoles

    Alberto Velasco Valdazo, alberto.velasco@hospitalreyjuancarlos.es

    Alberto Velasco Valdazo

    Recruiting

  • H. Morales Meseguer

    Murcia

    Felipe de Arriba de la Fuente, farriba@um.es

    Felipe de Arriba de la Fuente

    Recruiting

  • H. Un. Virgen de la Arrixaca

    Murcia

    Valentín Cabañas Perianes, valentin.cabanas@gmail.com

    Valentín Cabañas Perianes

    Recruiting

  • Hospital General Universitario Santa Lucía

    Murcia

    Completed

  • Complejo Hospitalario Universitario de Ourense

    Ourense

    Completed

  • Hospital Universitario Central de Asturias

    Oviedo

    Ana Pilar González Rodríguez, Dr, +34 985 108 000, anapilargonzalez@gmail.com; apayer.angel@gmail.com

    Ana Pilar González Rodríguez

    Recruiting

  • Hospital Son Llatzer

    Palma de Mallorca

    Joan Bargay Llenonart, jbargay@hsll.es

    Joan Bargay Llenonart

    Recruiting

  • Hospital Universitari Son Espases

    Palma de Mallorca

    Antonia Sampol Mayol, Dr, 971 175000, antonia.sampolm@ssib.es

    Antonia Sampol Mayol

    Recruiting

  • Clinica Universidad Navarra (CUN)

    Pamplona, Navarre, 31008

    Jesus San Miguel Izquierdo, sanmiguel@unav.es

    Jesus San Miguel Izquierdo

    Recruiting

  • Complejo Hospitalario de Navarra

    Pamplona

    Jose María Arguiñano Pérez, Dr, 948 25 54 00, jm.arguinano.perez@cfnavarra.es

    Jose María Arguiñano Pérez

    Recruiting

  • Complejo Hospitalario de Pontevedra

    Pontevedra

    Ana María Dios Loureiro, Dr, 986 800050, adiolou@gmail.com

    Ana María Dios Loureiro

    Recruiting

  • Hospital Universitario Quirón Salud Madrid

    Pozuelo de Alarcón, Madrid, 28223

    Carmen Martínez Chamorro, carmenmartinezchamorro@quironsalud.es ; carmenmartinezchanomorro@hotmail.com

    Carmen Martínez Chamorro

    Recruiting

  • Hospital Clinico Universitario Salamanca

    Salamanca, 37007

    Mª Victoria Mateos Manteca, Dr, mvmateos@usal.es

    Mª Victoria Mateos Manteca

    Recruiting

  • Hospital Universitario de Canarias

    San Cristóbal de La Laguna

    Sunil Lakhwani, mthernan@ull.es/mailto:sunillakhwani@hotmail.com

    Sunil Lakhwani

    Recruiting

  • Hospital Universitario de Donostia

    San Sebastián

    Maialen Sirvent Auzmendi, Dr, 943 007000, MAIALEN.SIRVENTAUZMENDI@osakidetza.eus

    Maialen Sirvent Auzmendi

    Recruiting

  • Hospital Universitario Infanta Sofía

    San Sebastián de los Reyes

    Eugenio Giménez Mesa, gimenezeu@yahoo.es

    Eugenio Giménez Mesa

    Recruiting

  • Complejo Hospitalario Universitario Nuestra Señora de la Candelaria

    Santa Cruz de Tenerife

    Pablo Ríos Rull, Dr, Pablo, pablo.riosrull@gmail.com; priosrul@ull.es

    Pablo Ríos Rull

    Recruiting

  • H. Universitario Marqués de Valdecilla

    Santander

    Enrique Ocio, Enriquem.ocio@scsalud.es

    Enrique Ocio

    Recruiting

  • Complejo Hospitalario Santiago (CHUS)

    Santiago de Compostela

    Marta Sonia González Pérez, marta.sonia.gonzalez.perez@sergas.es

    Marta Sonia González Pérez

    Recruiting

  • Hospital General de Segovia

    Segovia

    Aránzazu García Mateo, Dr, + 34 921 41 91 00, aranzazugarciamateo@hotmail.com

    Aránzazu García Mateo

    Recruiting

  • Complejo Hospitalario Regional Virgen Del Rocío

    Seville

    Estrella Carrillo Cruz, Dr, estrellacarrillocruz@gmail.com

    Estrella Carrillo Cruz

    Recruiting

  • H. Universitario de Valme

    Seville

    María del Carmen Couto Caro, mariac.couto.sspa@juntadeandalucia.es

    María del Carmen Couto Caro

    Recruiting

  • Hospital Universitario Reina Sofía

    Seville

    Miguel Ángel Álvarez Rivas, Dr, mangel.alvarez.sspa@juntadeandalucia.es

    Miguel Ángel Álvarez Rivas

    Recruiting

  • Hospital Universitari de Tarragona Joan XXIII

    Tarragona

    Josep Sarrà Escarré, jsarra@iconcologia.net

    Josep Sarrà Escarré, Dr

    Recruiting

  • Hospital Universitari Mutua Terrassa

    Terrassa

    Josep Mª Martí Tutusaus, Dr, + 34 93 736 50 50, jmarti@mutuaterrassa.es

    Josep Mª Martí Tutusaus

    Recruiting

  • Complejo Hospitalario de Toledo (Virgen de la Salud)

    Toledo

    Felipe Casado Montero, Dr, 925 269243, lfcasadom@telefonica.net

    Felipe Casado Montero

    Recruiting

  • Hospital Clínico Universitario de Valencia

    Valencia

    Ana Isabel Teruel Casasus, Dr, 961 973838, ateruelc@hotmail.com

    Ana Isabel Teruel Casasus

    Recruiting

  • Hospital Universitari i Politecnic la Fe

    Valencia

    Mario Arnao Herraiz, Dr, 96 1244192, arnao_mar@gva.es

    Mario Arnao Herraiz

    Recruiting

  • Hospital Universitario Dr. Peset Aleixandre

    Valencia

    Paz Ribas García, Dr, 963 862500, ribas_paz@gva.es

    Paz Ribas García

    Recruiting

  • H. U. Txagorritxu

    Vitoria-Gasteiz

    Xabier Gutierrez López de Ocariz, Dr, XABIER.GUTIERREZLOPEZDEOCARIZ@osakidetza.eus

    Xabier Gutierrez López de Ocariz

    Recruiting

  • Hospital Clinico Universitario Lozano Blesa

    Zaragoza

    Luis Ramón Palomera Bernal, Dr, 34 976 556 400, lpalomera@salud.aragon.es

    Luis Ramón Palomera Bernal

    Recruiting

  • Hospital Universitario Miguel Servet

    Zaragoza

    Ana Cristina Godoy Molias, anagodoy1006@hotmail.com

    Ana Cristina Godoy Molias

    Recruiting

Other trials in Spain

About this study

Official title: GEM21menos65. A Phase III Trial for NDMM Patients Who Are Candidates for ASCT Comparing Extended VRD Plus Early Rescue Intervention vs Isatuximab-VRD vs Isatuximab-V-Iberdomide-D

This is a Phase III open-label, 3-arm, parallel, randomized, controlled trial. The allocation ratio 1:1:1 and outcome assessment are blind to group allocation. Patients will be randomized from 3 arms. Patients will receive VRD extended + ASCT plus ERI or Isatuximab-VRD + ASCT or Isatuximab-VID + ASCT.

Read the detailed description

Patients will receive induction treatment, which will consist: arm A (Isatuximab-VRD + ASCT) or arm B (VRD extended + ASCT plus ERI) or arm C (Isatuximab-VID + ASCT). After ASTC, patients will start consolidation which will be 2 cycles of similar treatment to induction.

Continuous treatment will follow after consolidation and patients will receive:

  • arm A: Lenalidomide and monthly Isatuximab until progression, unacceptable toxicity, patient withdrawal, loss to follow up or death. During continuous treatment, dexamethasone 40 mg is used as a standardized premedication for Isatuximab.
  • arm B: after 6 cycles of induction VRD, ASCT and two consolidation VRDs, treatment continues with 10 additional cycles of VRD. During the extension cycles, VRD changes the bortezomib and dexamethasone regimen. In these10 cycles, both bortezomib and dexamethasone will be administered, at the same doses as the previous ones, but on a weekly schedule, on days 1, 8, 15 and 22 of each cycle. The lenalidomide regimen remains unchanged.
  • arm C: Iberdomide and monthly Isatuximab until progression, unacceptable toxicity, patient withdrawal, loss to follow up or death. During continuous treatment, dexamethasone 40 mg is used as a standardized premedication for Isatuximab.

The primary objective is to compare the efficacy of extended VRD + ASCT plus ERI (Arm B) vs. Isatuximab-VRD + ASCT (Arm A) in terms of proportion of patients who are MRD-negative by next generation flow cytometry (NGF) after 18 cycles + ASCT.

The primary endpoint, the MRD rate, takes as a reference the evaluation after the last extended VRD cycle, this is: 6 cycles for induction, 6 months for transplantation, 2 cycles for consolidation and 10 cycles until completing the 18 cycles of VRD, (in total about 24 months). For this reason,the primary endpoint in Arms A and C are established after a similar treatment time, which includes 4 cycles of induction, ASCT, 2 cycles of consolidation and 12 cycles of continuous treatment with Iberdomide plus Isatuximab (Dexamethasone to be determined).In patients of Arm B included in ERI, due to the great variability of the possible moments of incorporation in this therapeutic program, only rules are established for the moment and the realization or not of the transplant. The evaluation of the results will be carried out separately in the patients included, butalso in conjunction with the rest of the patients in Arm B to know the effect of the global strategy.

After the evaluation of the primary endpoint, continuous/maintenance treatment continues in Arms A, B and C, including patients in ARM B assigned to the ERI program. Obtaining conventional CR in either arm will require a BM analysis for MRD. In the case of stable response or improvement without RC, MRD controls have been pre-established. Due to the lack of data on tolerance and adherence to long-term treatment with Isatuximab and Iberdomide, changes in the therapeutic programs, for this reason, a complete revision of the therapeutic program has been predetermined at the moment in which the last patient included in the clinical trial reaches 36 months of treatment. At this point, taking into account the updated knowledge about continuous or maintenance treatments, the strategies for a second clinical trial or an extension of this clinical trial will be defined.

Being tested
Bortezomib, Isatuximab, Iberdomide, Lenalidomide, Dexamethasone

What participants receive

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

Study groups in NCT05558319
Study groupRoleWhat they receive
Control arm (A)Active comparatorINDUCTION: Isatuximab + VRD, 4 cycles. Isatuximab (IV) 10 mg/Kg, 1st cycle D: 1,8,15, 22. Cycles 2-4: D 1,15. Bortezomib (SC) 1.3 mg/m2, D:1, 4, 8, 11. Lenalidomide (PO) 25mg, D:1-21. Dexamethasone (PO) 40 mg, D: 1-4, 9-12. ASCT. The conditioning regimen is melphalan 200 mg/m2. CONSOLIDATION: Isatuximab + VRD, 2 cycles. Isatuximab (IV) 10 mg/Kg. D 1-15. Bortezomib (SC) 1.3 mg/m2, D:1, 4, 8, 11. Lenalidomide (PO) 25mg, D:1-21. Dexamethasone (PO) 40 mg, D: 1-4, 9-12. CONTINUOUS TREATMENT: Lenalidomide and monthly Isatuximab until progression, unacceptable toxicity, patient withdrawal, loss to follow up or death. During continuous treatment, dexamethasone 40 mg is used as a standardized premedication for Isatuximab.
Receives: Drug: Bortezomib; Drug: Isatuximab; Drug: Lenalidomide; Drug: Dexamethasone
EXPERIMENTAL ARM (B): Extended VRD and Early Rescue InterventionExperimentalINDUCTION: Includes two experimental lines: 1. VRD extended to 18 cycles: Induction (VRDx6): Bortezomib (SC) 1.3 mg/m2, D: 1, 4, 8, and 11 (Q4W). Lenalidomide 25 mg (PO), D: 1-21 (Q4W). Dexamethasone 40 mg (PO) D 1 to 4 and 9 to 12 (Q4W). Isatuximab (IV) 10 mg/kg, D: 1, 8, 15, and 22 (Q4W) and D: 1-15 in subsequent cycles. 2. Early detection of treatment failure and Early Rescue Intervention (ERI): Isatuximab-Iberdomide-Dexamethasone in continuous treatment. Isatuximab (IV) 10mg/kg Cycle 1: Days 1, 8, 15, and 22 (Q4W). Cycles 2 onwards: Days 1 and 15 (Q4W). Isatuximab will be infused monthly after 1 year treatment (Day 1 Q4W) including ASCT. Iberdomide (PO) 1,6 mg. D: 1-21 (Q4W). Dexamethasone (PO) 40 mg. D: 1, 8, 15, and 22 (Q4W). ASCT. The conditioning regimen is melphalan 200 mg/m2. CONSOLIDATION (VRDx2)- Extended VRD: VDx10, followed by lenalidomide plus dexamethasone maintenance. CONTINUOUS TREATMENT: Lenalidomide 15 mg, D: 1-21, and dexamethasone 20 mg, D: 1-4 (Q4W).
Receives: Drug: Bortezomib; Drug: Isatuximab; Drug: Iberdomide; Drug: Lenalidomide; Drug: Dexamethasone
EXPLORATORY ARM (C)ExperimentalINDUCTION: Iberdomide plus Isatuximab, bortezomib and dexamethasone (four cycles). Isatuximab (IV) 10 mg/kg D 1, 8, 15, and 22 in the first Q4W; and days 1-15 in subsequent cycles. Iberdomide (PO) at 1.6 mg on days 1-21 of every 4-week cycle. Bortezomib (SC) at 1.3 mg/m2 on days 1, 4, 8, and 11 of every 4-week cycle. Dexamethasone 40 mg (PO) D 1-4, 9-12 (Q4W). ASCT. The conditioning regimen is melphalan 200 mg/m2. CONSOLIDATION: two cycles (Q4W) of Isatuximab, Iberdomide, Bortezomib and Dexamethasone, as in induction, starting approximately 2 months after hospital discharge or 3 months after transplantation. Isatuximab will be infused monthly since the start of continuous therapy (after the second cycle of consolidation). CONTINUOUS TREATMENT: Iberdomide and monthly Isatuximab until progression, unacceptable toxicity, patient withdrawal, loss to follow up or death. During continuous treatment, dexamethasone 40 mg is used as a standardized premedication for Isatuximab.
Receives: Drug: Bortezomib; Drug: Isatuximab; Drug: Iberdomide; Drug: Dexamethasone

What is being measured

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

  1. Efficacy in terms of patients who are MRD-negative by NGF

    Percentage of patients who are MRD-negative by next generation flow cytometry (NGF) after 18 cycles + ASCT comparing the efficacy of extended VRD + ASCT plus ERI \& (Arm B) vs. IsatuximabVRD + ASCT (Arm A).

    Measured: 24 months

Secondary outcomes (2)

  1. Frequency of adverse events (AEs)

    Number of patients who presented AEs in each arm to perform safety analysis. NOTE: Due to the experimental nature of the Arm C combination Isatuximab-Iberdomide-Bortezomib-Dex, a safety analysis will be performed with the first 5 patients included in each arm as per section, a second one when 25 patients in each arm have completed 3 cycles of therapy, and subsequent ones might be required if considered by the Primary-Investigator, Co-Primary-Investigator, Co-coordinators and Co-Investigator.

    Measured: Throughout the study. Approximately 78 months.

  2. Progression-Free Survival (PFS)

    Time from the start of treatment until the earliest date of documented disease progression or death due to any cause.

    Measured: Throughout the study. Approximately 78 months

Timeline

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

  1. First posted28 Sep 2022
  2. Study start10 Nov 2022
  3. Primary completionApr 2027 (estimated)
  4. Study completionApr 2029 (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
480 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05558319
Sponsor's protocol ID
GEM21menos65
Acronym
GEM21menos65
Status last verified
Jun 2026
First submitted
23 Sep 2022
Last updated
25 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, Thakuri M, Reu F, Reynolds CM, Sexton R, Orlowski RZ, Barlogie B, Dispenzieri A. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017 Feb 4;389(10068):519-527. doi: 10.1016/S0140-6736(16)31594-X. Epub 2016 Dec 23.

    PubMed 28017406

  • Attal M, Lauwers-Cances V, Hulin C, Leleu X, Caillot D, Escoffre M, Arnulf B, Macro M, Belhadj K, Garderet L, Roussel M, Payen C, Mathiot C, Fermand JP, Meuleman N, Rollet S, Maglio ME, Zeytoonjian AA, Weller EA, Munshi N, Anderson KC, Richardson PG, Facon T, Avet-Loiseau H, Harousseau JL, Moreau P; IFM 2009 Study. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. N Engl J Med. 2017 Apr 6;376(14):1311-1320. doi: 10.1056/NEJMoa1611750.

    PubMed 28379796

  • Rosinol L, Oriol A, Rios R, Sureda A, Blanchard MJ, Hernandez MT, Martinez-Martinez R, Moraleda JM, Jarque I, Bargay J, Gironella M, de Arriba F, Palomera L, Gonzalez-Montes Y, Marti JM, Krsnik I, Arguinano JM, Gonzalez ME, Gonzalez AP, Casado LF, Lopez-Anglada L, Paiva B, Mateos MV, San Miguel JF, Lahuerta JJ, Blade J. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma. Blood. 2019 Oct 17;134(16):1337-1345. doi: 10.1182/blood.2019000241.

    PubMed 31484647

  • Rosinol L, Oriol A, Teruel AI, Hernandez D, Lopez-Jimenez J, de la Rubia J, Granell M, Besalduch J, Palomera L, Gonzalez Y, Etxebeste MA, Diaz-Mediavilla J, Hernandez MT, de Arriba F, Gutierrez NC, Martin-Ramos ML, Cibeira MT, Mateos MV, Martinez J, Alegre A, Lahuerta JJ, San Miguel J, Blade J; Programa para el Estudio y la Terapeutica de las Hemopatias Malignas/Grupo Espanol de Mieloma (PETHEMA/GEM) group. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood. 2012 Aug 23;120(8):1589-96. doi: 10.1182/blood-2012-02-408922. Epub 2012 Jul 12.

    PubMed 22791289

  • Rosinol L, Hebraud B, Oriol A, Colin AL, Rios Tamayo R, Hulin C, Blanchard MJ, Caillot D, Sureda A, Hernandez MT, Arnulf B, Mateos MV, Macro M, San-Miguel J, Belhadj K, Lahuerta JJ, Garelik MB, Blade J, Moreau P. Integrated analysis of randomized controlled trials evaluating bortezomib + lenalidomide + dexamethasone or bortezomib + thalidomide + dexamethasone induction in transplant-eligible newly diagnosed multiple myeloma. Front Oncol. 2023 Nov 2;13:1197340. doi: 10.3389/fonc.2023.1197340. eCollection 2023.

    PubMed 38023148

  • Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004 Apr;121(4):482-8. doi: 10.1309/74R4-TB90-BUWH-27JX.

    PubMed 15080299

  • van de Donk NW, Janmaat ML, Mutis T, Lammerts van Bueren JJ, Ahmadi T, Sasser AK, Lokhorst HM, Parren PW. Monoclonal antibodies targeting CD38 in hematological malignancies and beyond. Immunol Rev. 2016 Mar;270(1):95-112. doi: 10.1111/imr.12389.

    PubMed 26864107

  • Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Mace S, Corzo KP, Campana F, Le-Guennec S, Dubin F, Anderson KC; ICARIA-MM study group. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019 Dec 7;394(10214):2096-2107. doi: 10.1016/S0140-6736(19)32556-5. Epub 2019 Nov 14.

    PubMed 31735560

  • Leypoldt LB, Besemer B, Asemissen AM, Hanel M, Blau IW, Gorner M, Ko YD, Reinhardt HC, Staib P, Mann C, Lutz R, Munder M, Graeven U, Peceny R, Salwender H, Jauch A, Zago M, Benner A, Tichy D, Bokemeyer C, Goldschmidt H, Weisel KC. Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) in front-line treatment of high-risk multiple myeloma: interim analysis of the GMMG-CONCEPT trial. Leukemia. 2022 Mar;36(3):885-888. doi: 10.1038/s41375-021-01431-x. Epub 2021 Nov 3. No abstract available.

    PubMed 34732857

  • Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, Plesner T, Yoon SS, Ben Yehuda D, Richardson PG, Goldschmidt H, Reece D, Lisby S, Khokhar NZ, O'Rourke L, Chiu C, Qin X, Guckert M, Ahmadi T, Moreau P; POLLUX Investigators. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Oct 6;375(14):1319-1331. doi: 10.1056/NEJMoa1607751.

    PubMed 27705267

  • Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, Walter-Croneck A, Moreau P, Mateos MV, Magen H, Belch A, Reece D, Beksac M, Spencer A, Oakervee H, Orlowski RZ, Taniwaki M, Rollig C, Einsele H, Wu KL, Singhal A, San-Miguel J, Matsumoto M, Katz J, Bleickardt E, Poulart V, Anderson KC, Richardson P; ELOQUENT-2 Investigators. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015 Aug 13;373(7):621-31. doi: 10.1056/NEJMoa1505654. Epub 2015 Jun 2.

    PubMed 26035255

  • Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Simpson DR, Gimsing P, Palumbo A, Garderet L, Cavo M, Kumar S, Touzeau C, Buadi FK, Laubach JP, Berg DT, Lin J, Di Bacco A, Hui AM, van de Velde H, Richardson PG; TOURMALINE-MM1 Study Group. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Apr 28;374(17):1621-34. doi: 10.1056/NEJMoa1516282.

    PubMed 27119237

  • Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, Mark TM, Qi M, Schecter J, Amin H, Qin X, Deraedt W, Ahmadi T, Spencer A, Sonneveld P; CASTOR Investigators. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Aug 25;375(8):754-66. doi: 10.1056/NEJMoa1606038.

    PubMed 27557302

  • Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Spicka I, Oriol A, Hajek R, Rosinol L, Siegel DS, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak AJ, San-Miguel JF, Ludwig H, Wang M, Maisnar V, Minarik J, Bensinger WI, Mateos MV, Ben-Yehuda D, Kukreti V, Zojwalla N, Tonda ME, Yang X, Xing B, Moreau P, Palumbo A; ASPIRE Investigators. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015 Jan 8;372(2):142-52. doi: 10.1056/NEJMoa1411321. Epub 2014 Dec 6.

    PubMed 25482145

  • Nooka AK, Kaufman JL, Muppidi S, Langston A, Heffner LT, Gleason C, Casbourne D, Saxe D, Boise LH, Lonial S. Consolidation and maintenance therapy with lenalidomide, bortezomib and dexamethasone (RVD) in high-risk myeloma patients. Leukemia. 2014 Mar;28(3):690-3. doi: 10.1038/leu.2013.335. Epub 2013 Nov 13.

    PubMed 24220275

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bortezomib, Isatuximab and Iberdomide in people with Newly Diagnosed Multiple Myeloma, run by PETHEMA Foundation at 68 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 40 inclusion and 33 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: looking for participants now, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 68 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?

Contact Carmen López-Carrero (0034 699 835 437, carmen@fundacionpethema.es), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy in terms of patients who are MRD-negative by NGF (time frame: 24 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 NCT05558319, which also lists 36 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 25 Jun 2026; AzTrials last refreshed its copy on 6 Nov 2026.

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