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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01208766




Registration number
NCT01208766
Ethics application status
Date submitted
23/09/2010
Date registered
24/09/2010
Date last updated
21/08/2024

Titles & IDs
Public title
Study to Compare VMP With HDM Followed by VRD Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma
Scientific 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
Secondary ID [1] 0 0
2009-017903-28
Secondary ID [2] 0 0
HOVON 95 MM
Universal Trial Number (UTN)
Trial acronym
HO95
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bortezomib, Melphalan, Prednisone (VMP)
Treatment: Drugs - 1 or 2 cycle(s) HDM (High Dose Melphalan)
Treatment: Drugs - 2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD)

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.

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.

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.


Treatment: Drugs: 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

Treatment: Drugs: 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.

Treatment: Drugs: 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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
For all registered patients: progression free survival (PFS) as defined by time from registration to progression or death from any cause (whichever occurs first).
Timepoint [1] 0 0
end of trial (last patient last visit)
Primary outcome [2] 0 0
For all patients included in R1; PFS as defined by time from randomization R1 to progression or death from any cause whichever comes first
Timepoint [2] 0 0
end of trial (last patient last visit)
Primary outcome [3] 0 0
For all patients included in R2; PFS as defined by time from randomization R2 to progression or death from any cause whichever comes first
Timepoint [3] 0 0
end of trial (last patient last visit)
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
end of trial (last patient last visit)
Secondary outcome [2] 0 0
Toxicity
Timepoint [2] 0 0
End of trial (last patient last visit)
Secondary outcome [3] 0 0
Response (PR, VGPR, CR and stringent CR), and improvement of response during the various stages of the treatment.
Timepoint [3] 0 0
end of trial (last patient last visit)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
AU-Brisbane-PAH - Brisbane
Recruitment hospital [2] 0 0
AU-Canberra-CANBERRAHOSPITAL - Canberra
Recruitment hospital [3] 0 0
AU-Melbourne-ALFRED - Melbourne
Recruitment hospital [4] 0 0
AU-Sydney-CONCORD - Sydney
Recruitment hospital [5] 0 0
AU-Sydney-NEPEAN - Sydney
Recruitment hospital [6] 0 0
Prince of Wales Hospital - Sydney
Recruitment hospital [7] 0 0
St George Hospital - Sydney
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Canberra
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Sydney
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Linz
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Austria
State/province [2] 0 0
Salzburg
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Austria
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Vienna
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Belgium
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Antwerpen
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Belgium
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Haine-Saint-Paul
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Belgium
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La Louvière
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Belgium
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Liège
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Belgium
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Mons
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Belgium
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Roeselare
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Belgium
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Saint-Ghislain
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Belgium
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Tournai
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Belgium
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Turnhout
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Czechia
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Brno
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Czechia
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Hradec
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Czechia
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Olomouc
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Czechia
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Ostrava
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Czechia
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Plzen
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Prague
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Aalborg
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Aarhus
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Copenhagen
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Herlev
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Odense
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Roskilde
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Helsingborg
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Istanbul
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Izmir
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Kayseri

Funding & Sponsors
Primary sponsor type
Other
Name
Stichting Hemato-Oncologie voor Volwassenen Nederland
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Stichting European Myeloma Network
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Gruppo Italiano Malattie EMatologiche dell'Adulto
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
DSMM (Deutsche Studiengruppe Multiples Myelom)
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
NMSG (Nordic Myeloma Study Group)
Address [4] 0 0
Country [4] 0 0
Other collaborator category [5] 0 0
Other
Name [5] 0 0
Central European Myeloma Study Group
Address [5] 0 0
Country [5] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pieter Sonneveld, Prof.
Address 0 0
Stichting Hemato-Oncologie voor Volwassenen Nederland
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.