Study of Treatment for Newly Diagnosed Multiple Myeloma Patients Older Than 65 Years With Sequential Melphalan/Prednisone/Velcade (MPV) Followed by Revlimid/Low Dose Dexamethasone (Rd) Versus Alternating Velcade/Melphalan/Prednisone (MPV) With Revlimid/Low Dose Dexamethasone

NCT ID: NCT01237249

Last Updated: 2017-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2016-05-31

Brief Summary

This is a national, multicenter, open-label, randomized, comparative study designed to compare, first, the TTP of the two treatment schemes proposed (MPV followed by Rd or MPV alternating with Rd) in newly diagnosed MM patients older than 65 years. This comparison will be performing in terms of both efficacy and safety. Up to 120 patients will be included in each treatment arm and evaluated at scheduled visits in up to 3 study periods: Pre-treatment, Treatment and Follow-up.

Primary outcome measure:

• To evaluate the efficacy in terms of time to progression (TTP) at 18 months of MPV and Rd used as either in a sequential or alternating approach in newly diagnosed MM patients older than 65 years.
• To evaluate the toxicity (safety and tolerability) of the sequential versus the alternating use of MPV and Rd.

Secondary outcome measure:

• To evaluate the response, duration of response, progression free survival (PFS), time to next therapy (TNT) and overall survival (OS) in the two different groups of patients.
• To identify, within the group of patients treated with the alternating scheme, the biological characteristics (including a comprehensive genomic analysis) of those patients resistant to one or the other, and patients refractory to both treatments

Detailed Description

The Pre-treatment period includes Screening visit. After providing written informed consent form to participate in the study, patients will be evaluated for eligibility during a screening period of 14 days (Days -14 to -1). If patients meet all inclusion and exclusion criteria will be randomized at the moment of entry in the trial in a 1:1 allocation to receive either MPV followed by Rd (Treatment Group A) or MPV alternating with Rd (Treatment Group B).

Patients in the Treatment Group A will receive nine cycles of MPV consisting on one 6-weeks cycle of Velcade (Bortezomib) as an intravenous bolus twice weekly (days 1, 4, 8, 11, 22, 25, 29 and 32) followed by a 10 day rest period (day 33 to 42), in combination with oral Melphalan, once daily on days 1 to 4 and oral Prednisone, once daily on days 1 to 4, followed by eight 4-weeks cycles of Velcade (Bortezomib) as an intravenous bolus on days 1, 8, 15 and 22 followed by a 6 day rest period (days 23 to 28), in combination with Melphalan and Prednisone per os once daily on days 1 to 4, followed by a 24-day rest period (days 5 to 28). After the nine MPV cycles, patients will receive nine cycles of Rd consisting on 4-weeks cycles, including Revlimid (lenalidomide), once daily on days 1-21 followed by a 7 day rest period (days 22 to 28) plus oral dexamethasone, once weekly on days 1,8,15 and 22, followed by a 6 day rest period (days 23 to 28).

Patients in the Treatment Group B will receive the same schedule of therapy, but the MPV cycles will be alternated with Rd cycles. In this treatment Group B, patients will be again randomized to start receiving either MPV or Rd as first cycle of therapy. Overall, patients will receive an identical number of cycles, nine cycles of MPV and nine of Rd. Patients randomized to Treatment Group A relapsing/progressing or with major toxicities under treatment with MPV will be crossover to receive Rd, but only after study coordinator approval.

During the Treatment Period, patients will be evaluated at day 1 of each cycle. After completion of the Treatment Period, all patients will be evaluated every 2 months thereafter.

Safety will be assessed by the monitoring of adverse events, physical examinations, vital signs measurements, and haematology and clinical chemistry test. Response to treatment will be based on EBMT an IMWG criteria. Response to treatment will be evaluated at day 1 of each induction cycle, and every 2 months during thereafter.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MPV followed by Revlimid/Low Dose Dexamethasone (Rd)

Melphalan/Prednisone/Velcade (MPV) followed by Revlimid/Low Dose Dexamethasone (Rd)

Group Type: ACTIVE_COMPARATOR

Melphalan

Intervention Type: DRUG

Prednisone

Intervention Type: DRUG

Velcade

Intervention Type: DRUG

Alternating MPV with Revlimid/Low Dose Dexamethasone

Alternating Velcade/Melphalan/Prednisone (MPV) with Revlimid/Low Dose Dexamethasone (Rd)

Group Type: EXPERIMENTAL

Revlimid

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Interventions

Melphalan

Intervention Type: DRUG

Prednisone

Intervention Type: DRUG

Velcade

Intervention Type: DRUG

Revlimid

Intervention Type: DRUG

Dexamethasone

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Written informed consent obtained before starting any study-specific procedure.

2. Symptomatic elderly MM newly diagnosed by EBMT criteria older than 65 years.

3. Performance status (ECOG) ≤ 2.

4. Have pre-treatment clinical laboratory values meeting the following criteria within 14 days of randomization:

• platelet count ≥ 75x109/L
• haemoglobin ≥ 8g/dL
• absolute neutrophil count (ANC) ≥ 1.0x109/L
• Serum bilirubin ≤ 1.5 mg/dL and alkaline phosphatise ≤ 2.5 x ULN AST, ALT ≤ 2.5 x ULN
• Serum creatinine ≤2,5 mg/dl

Exclusion Criteria

1. Patient previously received treatment with Velcade or Revlimid.

2. Patient previously received treatment for Multiple Myeloma.

3. Patient has ≥ Grade 2 peripheral neuropathy within 14 days before enrolment.

4. Patient has hypersensitivity to bortezomib, boron, mannitol or lenalidomide.

5. Patient has received other investigational drugs with 28 days before enrolment.

6. Patient had a myocardial infarction within 6 months of enrolment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.

7. Patient currently is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.

8. Radiation therapy within 30 days before randomization, at least patient has had antialgic radiation. Radiation therapy will be afterwards permitted during the treatment period if it is indicated due to the presence of plasmacytomas

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag Ltd.

INDUSTRY

Sponsor Role: collaborator

Celgene

INDUSTRY

Sponsor Role: collaborator

TFS Trial Form Support

INDUSTRY

Sponsor Role: collaborator

PETHEMA Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

H. Son Llatzer

Palma de Mallorca, Balearic Islands, Spain

H. Vall d'Hebron, Barcelona

Barcelona, Barcelona, Spain

ICO - Duran i Reynals, Hospitalet de Llobregat

Barcelona, Barcelona, Spain

Hospital General de Castellón

Castellon, Castellón, Spain

Hospital Principe de Asturias

Alcalá de Henares, Madrid, Spain

Hospital Ramón y Cajal

Madrid, Madrid, Spain

Clínica Universitaria de Navarra

Pamplona, Navarre, Spain

Hospital Joan XXIII

Tarragona, Tarragona, Spain

Hospital Universitario Dr. Peset

Valencia, Valencia, Spain

Miguel Servet

Zaragoza, Zaragoza, Spain

Fundación Hospital Alcorcón

Alcorcón, , Spain

Hospital de Badalona Germans Trias i Pujol

Badalona, , Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital de Cruces

Bilbao, , Spain

Hospital Puerta del Mar

Cadiz, , Spain

Complejo Hospitalario de Cáceres

Cáceres, , Spain

Hospital General

Ciudad Real, , Spain

Hospital Virgen de la Luz

Cuenca, , Spain

Hospital Donostia

Donostia / San Sebastian, , Spain

Hospital Francesc Borja

Gandia, , Spain

ICO - Josep Trueta

Girona, , Spain

Hospital General de Guadalajara

Guadalajara, , Spain

H. de Jerez

Jerez de la Frontera, , Spain

Complejo Hospitalario León

León, , Spain

Clínica Puerta de Hierro

Madrid, , Spain

Hospital 12 de Octubre. Madrid

Madrid, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital de Fuenlabrada

Madrid, , Spain

Hospital de la Princesa

Madrid, , Spain

Hospital de Madrid, S.A.- Norte Hospital General

Madrid, , Spain

Hospital del Tajo

Madrid, , Spain

Hospital Infanta Leonor

Madrid, , Spain

Hospital Infanta Sofia

Madrid, , Spain

Hospital la Paz

Madrid, , Spain

Hospital Severo Ochoa

Madrid, , Spain

Hospital Universitario Gregorio Marañón

Madrid, , Spain

MD Anderson

Madrid, , Spain

Althaia

Manresa, , Spain

Complejo Hospital Costa del Sol

Málaga, , Spain

Hospital Nuestra Señora de Valme

Málaga, , Spain

Hospital General Univeristario Morales Messeguer

Murcia, , Spain

Hospital Virgen de la Arrixaca

Murcia, , Spain

Hospital de la Diputación de Navarra

Navarra, , Spain

Hospital de Gran Canaria Doctor Negrín

Palma de Gran Canaria, , Spain

Complejo Asistencial Son Dureta

Palma de Mallorca, , Spain

Hospital Virgen del Camino

Pamplona, , Spain

Corporació Sanitaria Parc Taulí

Sabadell, , Spain

Hospital Clínico de Salamanca

Salamanca, , Spain

Hospital Universitario de Canarias

Santa Cruz de Tenerife, , Spain

Hoaspital Marqués de Valdecilla

Santander, , Spain

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, , Spain

Hospital General de Segovia

Segovia, , Spain

Complejo Hospitalario Regional Virgen del Rocío

Seville, , Spain

Hospital Nuestra Señora del Prado

Toledo, , Spain

Hospital Virgen de la Salud

Toledo, , Spain

Hospital Arnau de Vilanova

Valencia, , Spain

Hospital Clínico de Valencia.

Valencia, , Spain

Hospital La Fe

Valencia, , Spain

Hospital Txagorritxu

Vitoria-Gasteiz, , Spain

Hospital Virgen de la Concha

Zamora, , Spain

Hospital Clinico Lozano Blesa

Zaragoza, , Spain

Countries

Spain

References

Quwaider D, Corchete LA, Misiewicz-Krzeminska I, Sarasquete ME, Perez JJ, Krzeminski P, Puig N, Mateos MV, Garcia-Sanz R, Herrero AB, Gutierrez NC. DEPTOR maintains plasma cell differentiation and favorably affects prognosis in multiple myeloma. J Hematol Oncol. 2017 Apr 18;10(1):92. doi: 10.1186/s13045-017-0461-8.

Reference Type: DERIVED

PMID: 28420429 (View on PubMed)

Paiva B, Cedena MT, Puig N, Arana P, Vidriales MB, Cordon L, Flores-Montero J, Gutierrez NC, Martin-Ramos ML, Martinez-Lopez J, Ocio EM, Hernandez MT, Teruel AI, Rosinol L, Echeveste MA, Martinez R, Gironella M, Oriol A, Cabrera C, Martin J, Bargay J, Encinas C, Gonzalez Y, Van Dongen JJ, Orfao A, Blade J, Mateos MV, Lahuerta JJ, San Miguel JF; Grupo Espanol de Mieloma/Programa para el Estudio de la Terapeutica en Hemopatias Malignas (GEM/PETHEMA) Cooperative Study Groups. Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients. Blood. 2016 Jun 23;127(25):3165-74. doi: 10.1182/blood-2016-03-705319. Epub 2016 Apr 26.

Reference Type: DERIVED

PMID: 27118453 (View on PubMed)

Paiva B, Corchete LA, Vidriales MB, Puig N, Maiso P, Rodriguez I, Alignani D, Burgos L, Sanchez ML, Barcena P, Echeveste MA, Hernandez MT, Garcia-Sanz R, Ocio EM, Oriol A, Gironella M, Palomera L, De Arriba F, Gonzalez Y, Johnson SK, Epstein J, Barlogie B, Lahuerta JJ, Blade J, Orfao A, Mateos MV, San Miguel JF; Spanish Myeloma Group / Program for the Study of Malignant Blood Diseases Therapeutics (GEM / PETHEMA) Cooperative Study Groups. Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance. Blood. 2016 Apr 14;127(15):1896-906. doi: 10.1182/blood-2015-08-665679. Epub 2016 Jan 11.

Reference Type: DERIVED

PMID: 26755711 (View on PubMed)

Related Links

http://aehh.org

Spanish Association of Hematology

Other Identifiers

GEM2010MAS65

Identifier Type: -

Identifier Source: org_study_id