Study to Compare VMP With HDM Followed by VRD Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma (HO95)

This study is currently recruiting participants.
Verified June 2011 by Stichting Hemato-Oncologie voor Volwassenen Nederland
Sponsor:
Collaborators:
European Myeloma Network
GIMEMA (Italian Group for Adult Hematologic Diseases)
DSMM (Deutsche Studiengruppe Multiples Myelom)
NMSG (Nordic Myeloma Study Group)
Central European Myeloma Study Group
Information provided by:
Stichting Hemato-Oncologie voor Volwassenen Nederland
ClinicalTrials.gov Identifier:
NCT01208766
First received: September 23, 2010
Last updated: June 16, 2011
Last verified: June 2011

September 23, 2010
June 16, 2011
January 2011
October 2014   (final data collection date for primary outcome 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) ] [ Designated as safety issue: Yes ]
  • For all patients included in R1; PFS as defined by time from randomization R1 to progression or death from any cause whichever comes first [ Time Frame: end of trial (last patient last visit) ] [ Designated as safety issue: Yes ]
  • For all patients included in R2; PFS as defined by time from randomization R2 to progression or death from any cause whichever comes first [ Time Frame: end of trial (last patient last visit) ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • For all patients included in R1; PFS as defined by time from randomization R1 to progression or death from any cause whichever comes first [ Time Frame: end of trial ] [ Designated as safety issue: Yes ]
  • For all patients included in R2; PFS as defined by time from randomization R2 to progression or death from any cause whichever comes first [ Time Frame: end of trial ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01208766 on ClinicalTrials.gov Archive Site
  • 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) ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: End of trial (last patient last visit) ] [ Designated as safety issue: Yes ]
  • 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) ] [ Designated as safety issue: No ]
  • Response (PR, VGPR, CR and stringent CR), and improvement of response during the various stages of the treatment [ Time Frame: end of trial ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: End of trial ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Study to Compare VMP With HDM Followed by VRD Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: Bortezomib, Melphalan, Prednisone (VMP)
    • Bortezomib _ 1.3 mg/m2 _ i.v. rapid infusion _ days 1,4,8,11,22,25,29,32
    • Melphalan _ 9 mg/m² _ p.o. _ days 1-4
    • Prednisone _ 60 mg/m² _ p.o. _ days 1-4
  • Drug: 1 or 2 cycle(s) HDM (High Dose Melphalan)

    - Melphalan _ 100 mg/m² _ i.v. rapid infusion _ -3, -2*

    *Patients with renal insufficiency 100 mg/m2 only at day -3

    If a patient is randomized to receive 2 x HDM a second course of High Dose Melphalan may be administered between 2 and 3 months after the first course when the patient achieved at least PR.

  • Drug: 2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD)
    • Bortezomib _ 1.3 mg/m2 _ i.v. rapid infusion _ days 1,4,8,11
    • Lenalidomide _ 25 mg _ p.o. _ days 1-21
    • Dexamethasone _ 20 mg _ p.o. _ days 1,2,4,5,8,9,11,12
  • Active Comparator: R1: 4 cycles Bortezomib, Melphalan, Prednisone (VMP)
    All 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.
    Intervention: Drug: Bortezomib, Melphalan, Prednisone (VMP)
  • Experimental: R1: 1 (2) cycle(s) HDM
    All 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.
    Intervention: Drug: 1 or 2 cycle(s) HDM (High Dose Melphalan)
  • No Intervention: R2: none
    No consolidation, patients will continue to Lenalidomide maintenance.
  • Experimental: R2: 2 cycles of VRD
    In 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.
    Intervention: Drug: 2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
1500
October 2015
October 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
No
Contact: Titia Gussinklo, Msc +31 (0)10 704 15 60 hdc@erasmusmc.nl
Contact: Petra Cornelisse, Msc +31 (0)10 704 15 60 hdc@erasmusmc.nl
Netherlands
 
NCT01208766
HOVON 95 MM, 2009-017903-28, EMN02
Yes
Prof. P. Sonneveld, HOVON
Stichting Hemato-Oncologie voor Volwassenen Nederland
  • European Myeloma Network
  • GIMEMA (Italian Group for Adult Hematologic Diseases)
  • DSMM (Deutsche Studiengruppe Multiples Myelom)
  • NMSG (Nordic Myeloma Study Group)
  • Central European Myeloma Study Group
Principal Investigator: Pieter Sonneveld, Prof. Stichting Hemato-Oncologie voor Volwassenen Nederland
Stichting Hemato-Oncologie voor Volwassenen Nederland
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP