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

Multiple Myeloma Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02406144
• Other study ID #: GEM2014MAIN
• Status: Completed
• Phase: Phase 3
• First received: March 25, 2015
• Last updated: November 28, 2017
• Start date: November 2014
• Est. completion date: November 2017

Study information

• Verified date: November 2017
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 316
• Est. completion date: November 2017
• Est. primary completion date: September 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 67 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• MLN9708

• Lenalidomide

• Dexamethasone

Locations

Country	Name	City	State
Spain	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	H.Universitari Germans Trias I Pujol de Badalona	Barcelona
Spain	Hospital Clinic	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	Complejo Hospitalario de Cáceres	Cáceres
Spain	Hospital de Especialidades de Jerez de La Frontera	Cádiz
Spain	Hospital Universitario Marqués de Valdecilla	Cantabria
Spain	Hospital General de Castellón	Castello
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)	Malaga
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	Sevilla
Spain	Hospital Virgen del Rocío	Sevilla
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

Sponsors (3)

Lead Sponsor	Collaborator
PETHEMA Foundation	Celgene, Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	Months to progression disease	5 years
Secondary	Minimal Residual Disease (MRD)	Number of patient with MRD and evaluation of its clinical significance	5 years
Secondary	Overall survival	Months of survival	6 years