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

November 28, 2017 updated by: PETHEMA Foundation

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

316

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • A Coruña, Spain
        • Complejo Hospitalario Universitario de Santiago
      • Alava, Spain
        • Hospital Txagorritxu
      • Albacete, Spain
        • Hospital General de Albacete
      • Alicante, Spain
        • Hospital General Universitario de Alicante
      • Alicante, Spain
        • Hospital del Vinalopó
      • Asturias, Spain
        • Hospital de Cabueñes
      • Asturias, Spain
        • Hospital Universitario Central de Asturias
      • Barcelona, Spain, 08036
        • Hospital Clínic
      • Barcelona, Spain
        • Hospital del Mar
      • Barcelona, Spain
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain
        • Hospital Vall d'Hebron
      • Barcelona, Spain
        • H.Universitari Germans Trias I Pujol de Badalona
      • Barcelona, Spain
        • Hospital de Sabadell (Parc Taulí)
      • Barcelona, Spain
        • Hospital de Sant Joan de Déu
      • Barcelona, Spain
        • Hospital Universitari Mutua de Terrasa
      • Barcelona, Spain
        • ICO l'Hospitalet
      • Burgos, Spain
        • Hospital Universitario de Burgos
      • Cantabria, Spain
        • Hospital Universitario Marques de Valdecilla
      • Castello, Spain
        • Hospital General de Castellon
      • Ciudad Real, Spain
        • Hospital General de Ciudad Real
      • Cáceres, Spain
        • Complejo Hospitalario de Caceres
      • Cádiz, Spain
        • Hospital de Especialidades de Jerez de La Frontera
      • GRAN Canaria, Spain
        • Hospital de Gran Canaria Doctor Negrin
      • Girona, Spain
        • Hospital Universitari Dr. Josep Trueta de Girona
      • Granada, Spain
        • Hospital Universitario Virgen de las Nieves
      • Guadalajara, Spain
        • Hospital Universitario Guadalajara
      • Guipúzcoa, Spain
        • Hospital Universitario Donostia
      • Illes Balears, Spain
        • Hospital Son Llatzer
      • Illes Balears, Spain
        • Hospital Universitari Son Espases
      • La Rioja, Spain
        • Hospital San Pedro
      • León, Spain
        • Hospital de Leon
      • Lleida, Spain
        • Hospital Universitari Arnau de Vilanova de Lleida
      • Madrid, Spain
        • Hospital General Universitario Gregorio Maranon
      • Madrid, Spain
        • Hospital Ramon y Cajal
      • Madrid, Spain
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain
        • Hospital Clinico San Carlos
      • Madrid, Spain
        • Hospital Universitario La Paz
      • Madrid, Spain
        • Hospital Universitario de La Princesa
      • Madrid, Spain
        • Hospital De Fuenlabrada
      • Madrid, Spain
        • Hospital Infanta Leonor
      • Madrid, Spain
        • Hospital del Tajo
      • Madrid, Spain
        • Hospital Universitario Puerta de Hierro Majadahonda
      • Madrid, Spain
        • Centro Oncologico MD Anderson International Espana
      • Madrid, Spain
        • Hospital Severo Ochoa
      • Madrid, Spain
        • Fundacion Jimenez Diaz-UTE
      • Madrid, Spain
        • Hospital Infanta Sofia
      • Madrid, Spain
        • Hospital Universitario Fundacion Alcorcon
      • Madrid, Spain
        • Hm Universitario San Chinarro
      • Madrid, Spain
        • Hospital Universitario Infanta Cristina
      • Malaga, Spain
        • Complejo Hospital Costa Del Sol (Ivcs)
      • Murcia, Spain
        • Hospital Universitario Virgen de la Arrixaca
      • Murcia, Spain
        • Hospital General Universitario Santa Lucia
      • Murcia, Spain
        • Hospital J.M. Morales Meseguer
      • Navarra, Spain
        • Clinica Universidad de Navarra
      • Navarra, Spain
        • Complejo Hospitalario de Navarra
      • Ourense, Spain
        • Complejo Hospitalario de Ourense
      • Pontevedra, Spain
        • Complejo Hospitalario de Pontevedra
      • Salamanca, Spain
        • Hospital Universitario de Salamanca
      • Santa Cruz de Tenerife, Spain
        • Hospital Universitario de Canarias
      • Segovia, Spain
        • Hospital General de Segovia
      • Sevilla, Spain
        • Hospital Virgen del Rocío
      • Sevilla, Spain
        • Hospital Nuestra Señora de Valme
      • Soria, Spain
        • Hospital Santa Bárbara
      • Tarragona, Spain
        • Hospital Universitari Joan Xxiii de Tarragona
      • Toledo, Spain
        • Complejo Hospitalario de Toledo
      • Toledo, Spain
        • Hospital Nuestra Señora del Prado
      • Valencia, Spain
        • Hospital Universitario Dr. Peset
      • Valencia, Spain
        • Hospital Universitario La Fe
      • Valencia, Spain
        • Hospital Clinico Universitario Valencia
      • Valladolid, Spain
        • Hospital Clínico Universitario de Valladolid
      • Valladolid, Spain
        • Hospital Universitario del Río Hortega
      • Vizcaya, Spain
        • Hospital de Cruces
      • Zaragoza, Spain
        • Hospital Universitario Miguel Servet
      • Zaragoza, Spain
        • Hospital Clinico Universitario Lozano Blesa

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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):

    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 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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
Drug: Lenalidomide
Drug: Dexamethasone
Experimental: 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.
Drug: Lenalidomide
Drug: Dexamethasone
Drug: MLN9708

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: 5 years
Months to progression disease
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minimal Residual Disease (MRD)
Time Frame: 5 years
Number of patient with MRD and evaluation of its clinical significance
5 years
Overall survival
Time Frame: 6 years
Months of survival
6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

PETHEMA Foundation

Collaborators

Millennium Pharmaceuticals, Inc.
Celgene

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2014

Primary Completion (Actual)

September 1, 2017

Study Completion (Actual)

November 1, 2017

Study Registration Dates

First Submitted

March 25, 2015

First Submitted That Met QC Criteria

March 29, 2015

First Posted (Estimate)

April 2, 2015

Study Record Updates

Last Update Posted (Actual)

November 30, 2017

Last Update Submitted That Met QC Criteria

November 28, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEM2014MAIN

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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