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.

• Register: Netherlands Trial Register
• Last refreshed on: 28 April 2013
• Main ID: NTR2528
• Date of registration: 21/09/2010
• Primary sponsor: HOVON Data Center
• Public 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.
• 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. - HOVON 95 MM
• Date of first enrolment: 1/10/2010
• Target sample size: 1500
• Recruitment status: pending
• URL: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2528
• Study type: intervention
• Study design: Randomised: Yes; Masking: None; Control: Active; Group: Parallel; Type: 2 or more arms, randomized

Countries of recruitment

The Netherlands

Contacts

• Name: P. Sonneveld

• Name: P. Sonneveld

Key inclusion & exclusion criteria

Inclusion criteria: 1. Patients with a confirmed diagnosis of symptomatic multiple myeloma stage I to III according to the International Staging System ISS, i.e. at least one of the CRAB criteria should be present;

2. Measurable disease as defined by the presence of M-protein in serum or urine (serum Mprotein > 10 g/l or urine M-protein > 200 mg/24 hours), or abnormal free light chain ratio;

3. Age 18-65 years inclusive;

4. WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and not by comorbid conditions);

5. Negative pregnancy test at inclusion if applicable;

6. Written informed consent.



Inclusion for randomisation 1:

1. WHO performance 0-2;

2. Bilirubin and transaminases < 2.5 times the upper limit of normal values;

3. A suitable stem cell graft containing at least 4 x 106 CD34+ cells/kg (or according to national guidelines).



Inclusion for randomisation 2:

1. Bilirubin and transaminases < 2.5 times the upper limit of normal values;

2. ANC >= 0.5 x 109/l and platelets > 20 x 10^9/l;

3. Patient is able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan.
Exclusion criteria: 1. Known intolerance of Boron;

2. Systemic AL amyloidosis;

3. Primary Plasmacell Leukemia;

4. Non-secretory MM;

5. Previous chemotherapy or radiotherapy except local radiotherapy in case of local myeloma progression or corticosteroids maximum 5 days for symptom control;

6. Severe cardiac dysfunction (NYHA classification II-IV, see appendix E);

7. Significant hepatic dysfunction, unless related to myeloma;

8. Patients with GFR <15 ml/min;

9. Patients known to be HIV-positive;

10. Patients with active, uncontrolled infections;

11. Patients with neuropathy, CTC grade 2 or higher;

12. 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;

13. Patients who are not willing or capable to use adequate contraception during the therapy (all men, all pre-menopausal women);

14. Lactating women.



Exclusion for randomisation 1:

1. Severe pulmonary, neurologic, or psychiatric disease;

2. CTCAE grade 3-4 polyneuropathy during Bortezomib treatment;

3. Allogeneic Stem Cell Transplantation (Allo SCT) planned;

4. Progressive disease.



Exclusion for randomisation 2:

1. Progressive disease;

2. Neuropathy, except CTCAE grade 1;

3. CTCAE grade 3-4 polyneuropathy during Bortezomib treatment.

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Multiple myeloma (Kahler's disease)

Intervention(s)

Patients with multiple myeloma, meeting all eligibility criteria will be registered on entry and treated with 3 induction cycles with VCD, followed by Cyclophosphamide for stem cell mobilization and collection.

After induction patients will be randomized to compare two intensification regimens VMP vs. HDM (R1), except if a patient will proceed to allogenic SCT. In hospitals with a policy of double intensification, all patients will be randomized at R1 between VMP, 1 HDM and 2 HDM, in order also to evaluate 1 HDM vs. 2 HDM.

After intensification treatment there will be a 2nd randomization to compare VRD consolidation vs. no consolidation (R2), followed by Lenalidomide maintenance in both arms.

Primary Outcome(s)

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);

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;

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.

Secondary Outcome(s)

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

2. 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;

3. Toxicity.

Secondary ID(s)

2009-017903-28

Source(s) of Monetary Support

Amgen, Dutch Cancer Society, Roche Nederland BV, Johnson&Johnson-Orthobiotech, Novartis

Secondary Sponsor(s)

Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON)