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
NCT ID: NCT02406144
Last Updated: 2017-11-30
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE3
316 participants
INTERVENTIONAL
2014-11-30
2017-11-30
Brief Summary
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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.
Detailed Description
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• 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.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Lenalidomide
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
Lenalidomide
Dexamethasone
MLN9708 plus Lenalidomide
MLN9708 during the two year maintenance period, at a dose of 4 mg/day on days 1, 8 and 15 of the cycle.
MLN9708
Lenalidomide
Dexamethasone
Interventions
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MLN9708
Lenalidomide
Dexamethasone
Eligibility Criteria
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Inclusion Criteria
* 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):
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.
2. Corrected serum calcium \< 14 mg/dL.
3. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x the upper limit of normal (ULN)
4. Total bilirubin within normal range
5. Calculated creatinine clearance \> 30 mL/min
* Female patients who:
1. Are postmenopausal for at least 1 year before the screening visit, OR
2. Are surgically sterile, OR
3. 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
4. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
5. 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:
1. Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
2. 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.)
Exclusion Criteria
* 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.
* 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.
18 Years
67 Years
ALL
No
Sponsors
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Celgene
INDUSTRY
Millennium Pharmaceuticals, Inc.
INDUSTRY
PETHEMA Foundation
OTHER
Responsible Party
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Locations
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Complejo Hospitalario Universitario de Santiago
A Coruña, , Spain
Hospital Txagorritxu
Alava, , Spain
Hospital General de Albacete
Albacete, , Spain
Hospital Del Vinalopo
Alicante, , Spain
Hospital General Universitario de Alicante
Alicante, , Spain
Hospital de Cabueñes
Asturias, , Spain
Hospital Universitario Central de Asturias
Asturias, , Spain
Hospital Clinic
Barcelona, , Spain
H.Universitari Germans Trias I Pujol de Badalona
Barcelona, , Spain
Hospital de La Santa Creu I Sant Pau
Barcelona, , Spain
Hospital de Sabadell (Parc Taulí)
Barcelona, , Spain
Hospital de Sant Joan de Déu
Barcelona, , Spain
Hospital Del Mar
Barcelona, , Spain
Hospital Universitari Mútua de Terrasa
Barcelona, , Spain
Hospital Vall D'Hebron
Barcelona, , Spain
Ico L'Hospitalet
Barcelona, , Spain
Hospital Universitario de Burgos
Burgos, , Spain
Hospital de Especialidades de Jerez de La Frontera
Cadiz, , Spain
Hospital Universitario Marqués de Valdecilla
Cantabria, , Spain
Hospital General de Castellón
Castelló, , Spain
Complejo Hospitalario de Cáceres
Cáceres, , Spain
Hospital General de Ciudad Real
Ciudad Real, , Spain
Hospital Universitari Dr. Josep Trueta de Girona
Girona, , Spain
Hospital de Gran Canaria Doctor Negrín
GRAN Canaria, , Spain
Hospital Universitario Virgen de Las Nieves
Granada, , Spain
Hospital Universitario Guadalajara
Guadalajara, , Spain
Hospital Universitario Donostia
Guipúzcoa, , Spain
Hospital Son Llatzer
Illes Balears, , Spain
Hospital Universitari Son Espases
Illes Balears, , Spain
Hospital San Pedro
La Rioja, , Spain
Hospital de León
León, , Spain
Hospital Universitari Arnau de Vilanova de Lleida
Lleida, , Spain
Centro Oncológico Md Anderson International España
Madrid, , Spain
Fundación Jiménez Díaz-Ute
Madrid, , Spain
Hm Universitario San Chinarro
Madrid, , Spain
Hospital Clínico San Carlos
Madrid, , Spain
Hospital de Fuenlabrada
Madrid, , Spain
Hospital Del Tajo
Madrid, , Spain
Hospital General Universitario Gregorio Marañón
Madrid, , Spain
Hospital Infanta Leonor
Madrid, , Spain
Hospital Infanta Sofía
Madrid, , Spain
Hospital Ramón Y Cajal
Madrid, , Spain
Hospital Severo Ochoa
Madrid, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Hospital Universitario de La Princesa
Madrid, , Spain
Hospital Universitario Fundación Alcorcón
Madrid, , Spain
Hospital Universitario Infanta Cristina
Madrid, , Spain
Hospital Universitario La Paz
Madrid, , Spain
Hospital Universitario Puerta de Hierro Majadahonda
Madrid, , Spain
Complejo Hospital Costa Del Sol (Ivcs)
Málaga, , Spain
Hospital General Universitario Santa Lucia
Murcia, , Spain
Hospital J.M. Morales Meseguer
Murcia, , Spain
Hospital Universitario Virgen de La Arrixaca
Murcia, , Spain
Clinica Universidad de Navarra
Navarra, , Spain
Complejo Hospitalario de Navarra
Navarra, , Spain
Complejo Hospitalario de Ourense
Ourense, , Spain
Complejo Hospitalario de Pontevedra
Pontevedra, , Spain
Hospital Universitario de Salamanca
Salamanca, , Spain
Hospital Universitario de Canarias
Santa Cruz de Tenerife, , Spain
Hospital General de Segovia
Segovia, , Spain
Hospital Nuestra Señora de Valme
Seville, , Spain
Hospital Virgen del Rocío
Seville, , Spain
Hospital Santa Bárbara
Soria, , Spain
Hospital Universitari Joan Xxiii de Tarragona
Tarragona, , Spain
Complejo Hospitalario de Toledo
Toledo, , Spain
Hospital Nuestra Señora Del Prado
Toledo, , Spain
Hospital Clínico Universitario Valencia
Valencia, , Spain
Hospital Universitario Dr. Peset
Valencia, , Spain
Hospital Universitario La Fe
Valencia, , Spain
HOSPITAL CLíNICO UNIVERSITARIO DE VALLADOLID
Valladolid, , Spain
Hospital Universitario Del Rio Hortega
Valladolid, , Spain
Hospital de Cruces
Vizcaya, , Spain
Hospital Clínico Universitario Lozano Blesa
Zaragoza, , Spain
Hospital Universitario Miguel Servet
Zaragoza, , Spain
Countries
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References
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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.
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.
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.
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.
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.
Other Identifiers
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GEM2014MAIN
Identifier Type: -
Identifier Source: org_study_id