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

NCT02406144 | Completed Phase 3 DMC

• 1 other identifier: GEM2014MAIN
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 74

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

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Months to progression disease

  5 years

Secondary Outcomes (2)

• Minimal Residual Disease (MRD)

  5 years

• Overall survival

  6 years

Study Arms (2)

Lenalidomide

ACTIVE COMPARATOR

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

Drug: Lenalidomide; Drug: Dexamethasone

MLN9708 plus Lenalidomide

EXPERIMENTAL

MLN9708 during the two year maintenance period, at a dose of 4 mg/day on days 1, 8 and 15 of the cycle.

Drug: MLN9708; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

MLN9708 DRUG

MLN9708 plus Lenalidomide

Lenalidomide DRUG

Lenalidomide; MLN9708 plus Lenalidomide

Dexamethasone DRUG

Lenalidomide; MLN9708 plus Lenalidomide

Eligibility Criteria

• Age: 18 Years - 67 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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.
• Known hypersensitivity to lenalidomide or to MLN9708, their analogues, or excipients in the various formulations of any agent.
• Patients who are currently participating in another clinical trial or receiving any other investigational product.
• Seropositive for HVB, HVC or HIV.

Sponsors & Collaborators

• PETHEMA Foundation: lead
• Celgene: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (74)

Complejo Hospitalario Universitario de Santiago

A Coruña, Spain

Location

Hospital Txagorritxu

Alava, Spain

Location

Hospital General de Albacete

Albacete, Spain

Location

Hospital Del Vinalopo

Alicante, Spain

Location

Hospital General Universitario de Alicante

Alicante, Spain

Location

Hospital de Cabueñes

Asturias, Spain

Location

Hospital Universitario Central de Asturias

Asturias, Spain

Location

Hospital Clinic

Barcelona, 08036, Spain

Location

H.Universitari Germans Trias I Pujol de Badalona

Barcelona, Spain

Location

Hospital de La Santa Creu I Sant Pau

Barcelona, Spain

Location

Hospital de Sabadell (Parc Taulí)

Barcelona, Spain

Location

Hospital de Sant Joan de Déu

Barcelona, Spain

Location

Hospital Del Mar

Barcelona, Spain

Location

Hospital Universitari Mútua de Terrasa

Barcelona, Spain

Location

Hospital Vall D'Hebron

Barcelona, Spain

Location

Ico L'Hospitalet

Barcelona, Spain

Location

Hospital Universitario de Burgos

Burgos, Spain

Location

Hospital de Especialidades de Jerez de La Frontera

Cadiz, Spain

Location

Hospital Universitario Marqués de Valdecilla

Cantabria, Spain

Location

Hospital General de Castellón

Castelló, Spain

Location

Complejo Hospitalario de Cáceres

Cáceres, Spain

Location

Hospital General de Ciudad Real

Ciudad Real, Spain

Location

Hospital Universitari Dr. Josep Trueta de Girona

Girona, Spain

Location

Hospital de Gran Canaria Doctor Negrín

GRAN Canaria, Spain

Location

Hospital Universitario Virgen de Las Nieves

Granada, Spain

Location

Hospital Universitario Guadalajara

Guadalajara, Spain

Location

Hospital Universitario Donostia

Guipúzcoa, Spain

Location

Hospital Son Llatzer

Illes Balears, Spain

Location

Hospital Universitari Son Espases

Illes Balears, Spain

Location

Hospital San Pedro

La Rioja, Spain

Location

Hospital de León

León, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, Spain

Location

Centro Oncológico Md Anderson International España

Madrid, Spain

Location

Fundación Jiménez Díaz-Ute

Madrid, Spain

Location

Hm Universitario San Chinarro

Madrid, Spain

Location

Hospital Clínico San Carlos

Madrid, Spain

Location

Hospital de Fuenlabrada

Madrid, Spain

Location

Hospital Del Tajo

Madrid, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Infanta Leonor

Madrid, Spain

Location

Hospital Infanta Sofía

Madrid, Spain

Location

Hospital Ramón Y Cajal

Madrid, Spain

Location

Hospital Severo Ochoa

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario de La Princesa

Madrid, Spain

Location

Hospital Universitario Fundación Alcorcón

Madrid, Spain

Location

Hospital Universitario Infanta Cristina

Madrid, Spain

Location

Hospital Universitario La Paz

Madrid, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, Spain

Location

Complejo Hospital Costa Del Sol (Ivcs)

Málaga, Spain

Location

Hospital General Universitario Santa Lucia

Murcia, Spain

Location

Hospital J.M. Morales Meseguer

Murcia, Spain

Location

Hospital Universitario Virgen de La Arrixaca

Murcia, Spain

Location

Clinica Universidad de Navarra

Navarra, Spain

Location

Complejo Hospitalario de Navarra

Navarra, Spain

Location

Complejo Hospitalario de Ourense

Ourense, Spain

Location

Complejo Hospitalario de Pontevedra

Pontevedra, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, Spain

Location

Hospital General de Segovia

Segovia, Spain

Location

Hospital Nuestra Señora de Valme

Seville, Spain

Location

Hospital Virgen del Rocío

Seville, Spain

Location

Hospital Santa Bárbara

Soria, Spain

Location

Hospital Universitari Joan Xxiii de Tarragona

Tarragona, Spain

Location

Complejo Hospitalario de Toledo

Toledo, Spain

Location

Hospital Nuestra Señora Del Prado

Toledo, Spain

Location

Hospital Clínico Universitario Valencia

Valencia, Spain

Location

Hospital Universitario Dr. Peset

Valencia, Spain

Location

Hospital Universitario La Fe

Valencia, Spain

Location

HOSPITAL CLíNICO UNIVERSITARIO DE VALLADOLID

Valladolid, Spain

Location

Hospital Universitario Del Rio Hortega

Valladolid, Spain

Location

Hospital de Cruces

Vizcaya, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Related Publications (5)

• 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.

  PMID: 39293025 DERIVED

• 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.

  PMID: 38048552 DERIVED

• 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.

  PMID: 38031761 DERIVED

• 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.

  PMID: 37506339 DERIVED

• 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.

  PMID: 34587246 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

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; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

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: March 25, 2015
• First Posted: April 2, 2015
• Study Start: November 1, 2014
• Primary Completion: September 1, 2017
• Study Completion: November 1, 2017
• Last Updated: November 30, 2017

Record last verified: 2017-11

Locations

ES (74)