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

NCT03742297 | Active Not Recruiting Phase 3

• 1 other identifier: GEM2017FIT
• Study Type: interventional
• Target: 462
• Locations: 1 country
• Sites: 58

Brief 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. 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).

Conditions

Newly Diagnosed Multiple Myeloma

Outcome Measures

Primary Outcomes (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,

  18 months

Study Arms (3)

VMP x 9 + Lenalidomida-dexamethasone x 9

ACTIVE COMPARATOR

Bortezomib-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

Drug: Lenalidomide.; Drug: Bortezomib; Drug: Dexamethasone; Drug: Prednisone; Drug: Melphalan

Carfilzomib-lenalidomida-dexamethasone regimen

EXPERIMENTAL

carfilzomib: 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

Drug: Lenalidomide.; Drug: Carfilzomib; Drug: Dexamethasone

Carfilzomib-lenalidomida-dexamethason with daratumumab

EXPERIMENTAL

Carfilzomib: 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

Drug: Lenalidomide.; Drug: Carfilzomib; Drug: Daratumumab; Drug: Dexamethasone

Interventions

Lenalidomide. DRUG

Lenalidomide

Carfilzomib-lenalidomida-dexamethason with daratumumab; Carfilzomib-lenalidomida-dexamethasone regimen; VMP x 9 + Lenalidomida-dexamethasone x 9

Carfilzomib DRUG

Carfilzomib

Carfilzomib-lenalidomida-dexamethason with daratumumab; Carfilzomib-lenalidomida-dexamethasone regimen

Bortezomib DRUG

Bortezomib

VMP x 9 + Lenalidomida-dexamethasone x 9

Daratumumab DRUG

Daratumumab

Carfilzomib-lenalidomida-dexamethason with daratumumab

Dexamethasone DRUG

Dexamethasone

Carfilzomib-lenalidomida-dexamethason with daratumumab; Carfilzomib-lenalidomida-dexamethasone regimen; VMP x 9 + Lenalidomida-dexamethasone x 9

Prednisone DRUG

Prednisone

VMP x 9 + Lenalidomida-dexamethasone x 9

Melphalan DRUG

Melphalan

VMP x 9 + Lenalidomida-dexamethasone x 9

Eligibility Criteria

• Age: 65 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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:
• 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).
• 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.

Sponsors & Collaborators

• PETHEMA Foundation: lead

Study Sites (58)

Complejo Hospitalario Universitario A Coruña

A Coruña, Spain

Location

Complejo Hospitalario Universitario de Albacete

Albacete, Spain

Location

Hospital General Universitario de Alicante

Alicante, Spain

Location

Hospital Universitari Germans Trias i Pujol (ICO Badalona)

Badalona, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitari Vall d´Hebron

Barcelona, Spain

Location

ICO L´Hospitalet

Barcelona, Spain

Location

Hospital Universitario de Cruces

Bilbao, Spain

Location

Complejo Hospitalario de Cáceres

Cáceres, Spain

Location

Complejo Hospitalario Regional Reina Sofía

Córdoba, Spain

Location

Hospital de Cabueñes

Gijón, Spain

Location

Hospital Universitari Dr. Josep Trueta (ICO Girona)

Girona, Spain

Location

Hospital de Especialidades de Jerez de la Frontera

Jerez de la Frontera, Spain

Location

Complejo Hospitalario Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, Spain

Location

Complejo Asistencial Universitario de León

León, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, Spain

Location

Hospital San Pedro

Logroño, Spain

Location

Complejo Hospitalario Lucus Augusti

Lugo, Spain

Location

Hospital 12 de octubre

Madrid, Spain

Location

Hospital clínico San Carlos

Madrid, Spain

Location

Hospital Ramón y Cajal

Madrid, Spain

Location

Hospital Universitario de la Princesa

Madrid, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, Spain

Location

Hospital Universitario Infanta Leonor

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, Spain

Location

HU Gregorio Marañón

Madrid, Spain

Location

Hospital San Joan de Deu (Althaia)

Manresa, Spain

Location

Hospital Costa del Sol

Málaga, Spain

Location

Hospital Virgen de la Victoria

Málaga, Spain

Location

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Spain

Location

Hospital General Universitario Morales Meseguer

Murcia, Spain

Location

Hospital General Universitario Santa Lucía

Murcia, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Spain

Location

Hospital Son Llatzer

Palma de Mallorca, Spain

Location

Hospital Universitario Son Espases

Palma de Mallorca, Spain

Location

Clinica Universitaria de Navarra

Pamplona, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Spain

Location

Complejo Hospitalario de Pontevedra

Pontevedra, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario de Donostia

San Sebastián, Spain

Location

Complejo Hospitalario Universitario Nuestra Señora de la Candelaria

Santa Cruz de Tenerife, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Spain

Location

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, Spain

Location

Hospital General de Segovia

Segovia, Spain

Location

H. Universitario Virgen de Rocío

Seville, Spain

Location

Hospital Nuestra Señona de Valme

Seville, Spain

Location

Hospital Universitari Joan XXIII de Tarragona

Tarragona, Spain

Location

Complejo Hospitalario de Toledo (Virgen de la Salud)

Toledo, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Spain

Location

Hospital Universitari i Politecnic la Fe

Valencia, Spain

Location

Hospital Universitario Dr. Peset Aleixandre

Valencia, Spain

Location

Complejo Hospitalario Universitario de Vigo

Vigo, Spain

Location

Hospital Txagorritxu

Vitoria-Gasteiz, Spain

Location

Hospital Clínico Lozano Blesa

Zaragoza, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Related Publications (1)

• 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.

  PMID: 40769684 DERIVED

MeSH Terms

Interventions

Lenalidomide; carfilzomib; Bortezomib; daratumumab; Dexamethasone; Prednisone; Melphalan

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Pregnadienediols; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Jesús F San Miguel

  Clínica Universidad de Navarra

  STUDY CHAIR

• Joan Blade, Dr

  Hospital Clinic of Barcelona

  STUDY CHAIR

• Juan Jose Lahuerta, Dr

  Hospital 12 de Octubre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2018
• First Posted: November 15, 2018
• Study Start: October 22, 2018
• Primary Completion: July 1, 2023
• Study Completion (Estimated): January 1, 2031
• Last Updated: September 14, 2022

Record last verified: 2022-09

Locations

ES (58)