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

January 16, 2017 updated by: PETHEMA Foundation

A National, Open-label, Multicenter, Randomized, Comparative Phase IIb 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 (Rd).

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

250

Phase

  • Phase 2

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
      • Alcorcón, Spain
        • Fundación Hospital Alcorcón
      • Badalona, Spain
        • Hospital de Badalona Germans Trias i Pujol
      • Barcelona, Spain
        • Hospital Del Mar
      • Barcelona, Spain
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain
        • Hospital Clinic i Provincial de Barcelona
      • Barcelona, Spain
        • H. Vall d'Hebron, Barcelona
      • Barcelona, Spain
        • ICO - Duran i Reynals, Hospitalet de Llobregat
      • Bilbao, Spain
        • Hospital de Cruces
      • Castellón, Spain
        • Hospital General de Castellon
      • Ciudad Real, Spain
        • Hospital General
      • Cuenca, Spain
        • Hospital Virgen De La Luz
      • Cáceres, Spain
        • Complejo Hospitalario de Caceres
      • Cádiz, Spain
        • Hospital Puerta del Mar
      • Donostia, Spain
        • Hospital Donostia
      • Gandía, Spain
        • Hospital Francesc Borja
      • Girona, Spain
        • ICO - Josep Trueta
      • Guadalajara, Spain
        • Hospital General de Guadalajara
      • Jerez de la Frontera, Spain
        • H. de Jerez
      • Leon, Spain
        • Complejo Hospitalario León
      • Madrid, Spain
        • Hospital Ramón y Cajal
      • Madrid, Spain
        • Hospital La Paz
      • Madrid, Spain
        • Hospital Clinico San Carlos
      • Madrid, Spain
        • Hospital De Fuenlabrada
      • Madrid, Spain
        • Hospital Infanta Leonor
      • Madrid, Spain
        • Hospital de La Princesa
      • Madrid, Spain
        • Hospital del Tajo
      • Madrid, Spain
        • Hospital Universitario Gregorio Marañon
      • Madrid, Spain
        • Hospital Severo Ochoa
      • Madrid, Spain
        • Hospital Infanta Sofia
      • Madrid, Spain
        • Clínica Puerta de Hierro
      • Madrid, Spain
        • Hospital 12 de Octubre. Madrid
      • Madrid, Spain
        • Hospital de Madrid, S.A.- Norte Hospital General
      • Madrid, Spain
        • MD Anderson
      • Manresa, Spain
        • Althaia
      • Murcia, Spain
        • Hospital Virgen de la Arrixaca
      • Murcia, Spain
        • Hospital General Univeristario Morales Messeguer
      • Málaga, Spain
        • Complejo Hospital Costa Del Sol
      • Málaga, Spain
        • Hospital Nuestra Señora de Valme
      • Navarra, Spain
        • Hospital de la Diputación de Navarra
      • Palma de Gran Canaria, Spain
        • Hospital de Gran Canaria Doctor Negrin
      • Palma de Mallorca, Spain
        • Complejo Asistencial Son Dureta
      • Pamplona, Spain
        • Hospital Virgen del Camino
      • Sabadell, Spain
        • Corporació Sanitària Parc Taulí
      • Salamanca, Spain
        • Hospital Clinico De Salamanca
      • Santander, Spain
        • Hoaspital Marqués de Valdecilla
      • Santiago de Compostela, Spain
        • Complejo Hospitalario Universitario de Santiago
      • Segovia, Spain
        • Hospital General de Segovia
      • Sevilla, Spain
        • Complejo Hospitalario regional Virgen del Rocio
      • Tarragona, Spain
        • Hospital Joan XXIII
      • Tenerife, Spain
        • Hospital Universitario de Canarias
      • Toledo, Spain
        • Hospital Virgen De La Salud
      • Toledo, Spain
        • Hospital Nuestra Señora del Prado
      • Valencia, Spain
        • Hospital Arnau de Vilanova
      • Valencia, Spain
        • Hospital Universitario Dr. Peset
      • Valencia, Spain
        • Hospital La Fe
      • Valencia, Spain
        • Hospital Clínico de Valencia.
      • Vitoria, Spain
        • Hospital Txagorritxu
      • Zamora, Spain
        • Hospital Virgen de la Concha
      • Zaragoza, Spain
        • Hospital Clinico Lozano Blesa
      • Zaragoza, Spain
        • Miguel Servet
    • Baleares
      • Palma de Mallorca, Baleares, Spain
        • H. Son Llàtzer
    • Madrid
      • Alcalá de Henares, Madrid, Spain
        • Hospital Principe de Asturias
    • Navarra
      • Pamplona, Navarra, Spain
        • Clínica Universitaria de Navarra

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

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: MPV followed by Revlimid/Low Dose Dexamethasone (Rd)
Melphalan/Prednisone/Velcade (MPV) followed by Revlimid/Low Dose Dexamethasone (Rd)
Drug: Prednisone
Drug: Melphalan
Drug: Velcade
Experimental: Alternating MPV with Revlimid/Low Dose Dexamethasone
Alternating Velcade/Melphalan/Prednisone (MPV) with Revlimid/Low Dose Dexamethasone (Rd)
Drug: Dexamethasone
Drug: Revlimid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
Time Frame: 18 months
18 months
To evaluate the toxicity (safety and tolerability) of the sequential versus the alternating use of MPV and Rd,in terms of adverse events presented in both groups of patients
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
To evaluate the response in both groups of patients
Time Frame: 1 year
1 year
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
Time Frame: 2 years
2 years
Duration of response in two groups of patients
Time Frame: 2 years
2 years
Progression free survival (PFS) in two different groups of patients
Time Frame: 18 months
18 months
Time to next therapy (TNT)
Time Frame: 2 years
2 years
Overall survival (OS) in the two different groups of patients
Time Frame: 5 years
5 years

Collaborators and Investigators

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

Sponsor

PETHEMA Foundation

Collaborators

Celgene
Janssen-Cilag Ltd.
TFS Trial Form Support

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

Helpful Links

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

February 1, 2011

Primary Completion (Actual)

August 1, 2014

Study Completion (Actual)

May 1, 2016

Study Registration Dates

First Submitted

November 4, 2010

First Submitted That Met QC Criteria

November 7, 2010

First Posted (Estimate)

November 9, 2010

Study Record Updates

Last Update Posted (Estimate)

January 18, 2017

Last Update Submitted That Met QC Criteria

January 16, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GEM2010MAS65

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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