Trial record 1 of 1 for:    NCT01208766
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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. (see Contacts and Locations)
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
  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.


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib, Melphalan, Prednisone (VMP)
Drug: 1 or 2 cycle(s) HDM (High Dose Melphalan)
Drug: 2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Stichting Hemato-Oncologie voor Volwassenen Nederland:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 1500
Study Start Date: January 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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
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.
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.

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.
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01208766

Contacts
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

Locations
Netherlands
Erasmus MC Recruiting
Rotterdam, Netherlands, 3075 EA
Contact: Pieter Sonneveld, Prof.    +31 (0)10 7033589    p.sonneveld@erasmusmc.nl   
Sponsors and Collaborators
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
Investigators
Principal Investigator: Pieter Sonneveld, Prof. Stichting Hemato-Oncologie voor Volwassenen Nederland
  More Information

Additional Information:
No publications provided

Responsible Party: Prof. P. Sonneveld, HOVON
ClinicalTrials.gov Identifier: NCT01208766     History of Changes
Other Study ID Numbers: HOVON 95 MM, 2009-017903-28, EMN02
Study First Received: September 23, 2010
Last Updated: June 16, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Stichting Hemato-Oncologie voor Volwassenen Nederland:
Multiple Myeloma (Kahler's disease)

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Melphalan
Prednisone
Thalidomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics

ClinicalTrials.gov processed this record on October 22, 2014