Clinical Trials /

Study to Compare VMP With HDM Followed by VRD Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma

NCT01208766

Description:

Study phase: phase III Study objective: - Comparison of Bortezomib, Melphalan, Prednisone (VMP) with High Dose Melphalan followed autologous stem cell transplantation (ASCT) - Comparison of Bortezomib, Lenalidomide, Dexamethasone(VRD) as consolidation versus no consolidation - Comparison of single versus tandem high dose Melphalan with ASCT Patient population: Patients with symptomatic multiple myeloma,previously untreated, ISS stages 1-3, age 18-65 years inclusive Study design: Prospective, multicenter, intergroup, randomized Duration of treatment: Expected duration of induction, stem cell collection and intensification is 6 - 9 months. Consolidation with VRD will last 2 months Maintenance therapy with Lenalidomide will be given until relapse. All patients will be followed until 10 years after registration.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study to Compare VMP With HDM Followed by VRD Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma
  • Official Title: A Randomized Phase III Study to Compare Bortezomib, Melphalan, Prednisone (VMP) With High Dose Melphalan Followed by Bortezomib, Lenalidomide, Dexamethasone (VRD) Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: HOVON 95 MM
  • SECONDARY ID: 2009-017903-28
  • SECONDARY ID: EMN02
  • NCT ID: NCT01208766

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
Bortezomib, Melphalan, Prednisone (VMP)R1: 4 cycles Bortezomib, Melphalan, Prednisone (VMP)
1 or 2 cycle(s) HDM (High Dose Melphalan)R1: 1 (2) cycle(s) HDM
2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD)R2: 2 cycles of VRD

Purpose

Study phase: phase III Study objective: - Comparison of Bortezomib, Melphalan, Prednisone (VMP) with High Dose Melphalan followed autologous stem cell transplantation (ASCT) - Comparison of Bortezomib, Lenalidomide, Dexamethasone(VRD) as consolidation versus no consolidation - Comparison of single versus tandem high dose Melphalan with ASCT Patient population: Patients with symptomatic multiple myeloma,previously untreated, ISS stages 1-3, age 18-65 years inclusive Study design: Prospective, multicenter, intergroup, randomized Duration of treatment: Expected duration of induction, stem cell collection and intensification is 6 - 9 months. Consolidation with VRD will last 2 months Maintenance therapy with Lenalidomide will be given until relapse. All patients will be followed until 10 years after registration.

Trial Arms

NameTypeDescriptionInterventions
R1: 4 cycles Bortezomib, Melphalan, Prednisone (VMP)Active ComparatorAll patients randomized to VMP treatment, will be treated with Bortezomib, Melphalan, Prednisone(VMP, 4 cycles) and will start intensification with VMP between 4 and 6 weeks after stem cell collection.
  • Bortezomib, Melphalan, Prednisone (VMP)
R1: 1 (2) cycle(s) HDMExperimentalAll patients randomized to intensification with High Dose Melphalan will start intensification with HDM (in hospitals with a policy of double intensification, patients will be randomized between VMP, 1 HDM and 2 HDM) between 4 and 6 weeks after stem cell collection.
  • 1 or 2 cycle(s) HDM (High Dose Melphalan)
R2: noneNo InterventionNo consolidation, patients will continue to Lenalidomide maintenance.
    R2: 2 cycles of VRDExperimentalIn patients randomized to consolidation treatment, 2 cycles of Bortezomib, Lenalidomide,Dexamethasone (VRD) will start at 8 weeks after the end of the last course of VMP or HDM.
    • 2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD)

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients with a confirmed diagnosis of symptomatic multiple myeloma stage I to III
                 according to the International Staging System ISS (see appendix A), i.e. at least one
                 of the CRAB criteria should be present;
    
              -  Measurable disease as defined by the presence of M-protein in serum or urine (serum
                 M-protein> 10 g/l or urine M-protein > 200 mg/24 hours), or abnormal free light chain
                 ratio;
    
              -  Age 18-65 years inclusive;
    
              -  WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and not by
                 comorbid conditions);
    
              -  Negative pregnancy test at inclusion if applicable;
    
              -  Written informed consent.
    
            Inclusion for randomisation 1:
    
              -  WHO performance 0-2;
    
              -  Bilirubin and transaminases < 2.5 times the upper limit of normal values;
    
              -  A suitable stem cell graft containing at least 4 x 106 CD34+ cells/kg (or according to
                 national guidelines).
    
            Inclusion for randomisation 2:
    
              -  Bilirubin and transaminases < 2.5 times the upper limit of normal values;
    
              -  ANC >= 0.5 x 109/l and platelets > 20 x 10^9/l;
    
              -  Patient is able to adhere to the requirements of the Lenalidomide Pregnancy Prevention
                 Risk Management Plan.
    
            Exclusion Criteria:
    
              -  Known intolerance of Boron;
    
              -  Systemic AL amyloidosis;
    
              -  Primary Plasmacell Leukemia;
    
              -  Non-secretory MM;
    
              -  Previous chemotherapy or radiotherapy except local radiotherapy in case of local
                 myeloma progression or corticosteroids maximum 5 days for symptom control;
    
              -  Severe cardiac dysfunction (NYHA classification II-IV);
    
              -  Significant hepatic dysfunction, unless related to myeloma;
    
              -  Patients with GFR <15 ml/min,
    
              -  Patients known to be HIV-positive;
    
              -  Patients with active, uncontrolled infections;
    
              -  Patients with neuropathy, CTC grade 2 or higher;
    
              -  Patients with a history of active malignancy during the past 5 years with the
                 exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
    
              -  Patients who are not willing or capable to use adequate contraception during the
                 therapy (all men, all pre-menopausal women);
    
              -  Lactating women.
    
            Exclusion for randomisation 1:
    
              -  Severe pulmonary, neurologic, or psychiatric disease;
    
              -  CTCAE grade 3-4 polyneuropathy during Bortezomib treatment;
    
              -  Allogeneic Stem Cell Transplantation (Allo SCT) planned;
    
              -  Progressive disease.'
    
            Exclusion for randomisation 2:
    
              -  Progressive disease;
    
              -  Neuropathy, except CTCAE grade 1;
    
              -  CTCAE grade 3-4 polyneuropathy during Bortezomib treatment.
          
    Maximum Eligible Age:65 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:For all registered patients: progression free survival (PFS) as defined by time from registration to progression or death from any cause (whichever occurs first).
    Time Frame:end of trial (last patient last visit)
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Overall survival measured from the time of registration /randomization R1/ randomization R2. Patients still alive or lost to follow up are censored at the date they were last known to be alive.
    Time Frame:end of trial (last patient last visit)
    Safety Issue:
    Description:
    Measure:Toxicity
    Time Frame:End of trial (last patient last visit)
    Safety Issue:
    Description:
    Measure:Response (PR, VGPR, CR and stringent CR), and improvement of response during the various stages of the treatment.
    Time Frame:end of trial (last patient last visit)
    Safety Issue:
    Description:

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Stichting Hemato-Oncologie voor Volwassenen Nederland

    Trial Keywords

    • Multiple Myeloma (Kahler's disease)

    Last Updated

    February 12, 2020