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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)

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ClinicalTrials.gov Identifier: NCT01208766
Recruitment Status : Active, not recruiting
First Posted : September 24, 2010
Last Update Posted : August 22, 2023
Sponsor:
Collaborators:
Stichting European Myeloma Network
Gruppo Italiano Malattie EMatologiche dell'Adulto
DSMM (Deutsche Studiengruppe Multiples Myelom)
NMSG (Nordic Myeloma Study Group)
Central European Myeloma Study Group
Information provided by (Responsible Party):
Stichting Hemato-Oncologie voor Volwassenen Nederland

Study Description
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Brief Summary:

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 or disease Intervention/treatment 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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1503 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : January 2011
Actual Primary Completion Date : December 2020
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. 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) ]
    For all registered patients: progression free survival (PFS) as defined by time from registration to progression or death from any cause (whichever occurs first).

  2. 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) ]
    For all patients included in R1; PFS as defined by time from randomization R1 to progression or death from any cause whichever comes first

  3. 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) ]
    For all patients included in R2; PFS as defined by time from randomization R2 to progression or death from any cause whichever comes first


Secondary Outcome Measures :
  1. 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) ]

    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.


  2. Toxicity [ Time Frame: End of trial (last patient last visit) ]
    Toxicity

  3. 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) ]
    Response (PR, VGPR, CR and stringent CR), and improvement of response during the various stages of the treatment.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01208766


Locations
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Sponsors and Collaborators
Stichting Hemato-Oncologie voor Volwassenen Nederland
Stichting European Myeloma Network
Gruppo Italiano Malattie EMatologiche dell'Adulto
DSMM (Deutsche Studiengruppe Multiples Myelom)
NMSG (Nordic Myeloma Study Group)
Central European Myeloma Study Group
Investigators
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Principal Investigator: Pieter Sonneveld, Prof. Stichting Hemato-Oncologie voor Volwassenen Nederland
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Cavo M, Gay F, Beksac M, Pantani L, Petrucci MT, Dimopoulos MA, Dozza L, van der Holt B, Zweegman S, Oliva S, van der Velden VHJ, Zamagni E, Palumbo GA, Patriarca F, Montefusco V, Galli M, Maisnar V, Gamberi B, Hansson M, Belotti A, Pour L, Ypma P, Grasso M, Croockewit A, Ballanti S, Offidani M, Vincelli ID, Zambello R, Liberati AM, Andersen NF, Broijl A, Troia R, Pascarella A, Benevolo G, Levin MD, Bos G, Ludwig H, Aquino S, Morelli AM, Wu KL, Boersma R, Hajek R, Durian M, von dem Borne PA, Caravita di Toritto T, Zander T, Driessen C, Specchia G, Waage A, Gimsing P, Mellqvist UH, van Marwijk Kooy M, Minnema M, Mandigers C, Cafro AM, Palmas A, Carvalho S, Spencer A, Boccadoro M, Sonneveld P. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study. Lancet Haematol. 2020 Jun;7(6):e456-e468. doi: 10.1016/S2352-3026(20)30099-5. Epub 2020 Apr 30. Erratum In: Lancet Haematol. 2020 Jun;7(6):e443. Lancet Haematol. 2020 Nov;7(11):e785.

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Responsible Party: Stichting Hemato-Oncologie voor Volwassenen Nederland
ClinicalTrials.gov Identifier: NCT01208766    
Other Study ID Numbers: HOVON 95 MM
2009-017903-28 ( EudraCT Number )
EMN02 ( Other Identifier: European Myeloma Network )
First Posted: September 24, 2010    Key Record Dates
Last Update Posted: August 22, 2023
Last Verified: August 2023
Keywords provided by Stichting Hemato-Oncologie voor Volwassenen Nederland:
Multiple Myeloma (Kahler's disease)
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
 Prednisone
Lenalidomide
Bortezomib
Melphalan
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents