Efficacy Study Comparing Velcade Dexamethasone Thalidomide Versus Velcade Cyclophosphamide Dexamethasone as Induction Treatment in the Initial Management of Multiple Myeloma (IFM2013-04)

Study Overview
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Brief Summary
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This is a phase III, multicenter, prospective with a clinical benefit, open-label and randomized study to compare two different treatments : Velcade (Bortezomib) Thalidomide Dexamethasone (VTD) versus Velcade (Bortezomib) Cyclophosphamide Dexamethasone (VCD) as an Induction Treatment prior to Autologous Stem Cell Transplantation in patients with Newly Diagnosed Multiple Myeloma. Eligible patients will be randomized into 2 treatment arms. Each patient will receive 4 consecutive 21 day cycles of an induction treatment with either VTD or VCD.

Detailed Description
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The patient population will consist of adult men and women who have a confirmed diagnosis of Multiple Myeloma and who meet eligibility criteria. They will be recruited from among the patients consulting in an investigating centre's haematology service for newly diagnosed, symptomatic, untreated multiple myeloma. in each treatment arm there will be : Induction therapy : 4 cycles of VTD (21 days)or VCD Systematic stem cell harvest after cycle 3

Official Title
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A PHASE III STUDY OF VELCADE (BORTEZOMIB) THALIDOMIDE DEXAMETHASONE (VTD) VERSUS VELCADE (BORTEZOMIB) CYCLOPHOSPHAMIDE DEXAMETHASONE (VCD) AS AN INDUCTION TREATMENT PRIOR TO AUTOLOGOUS STEM CELL TRANSPLANTATION IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA.

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Thalidomide®
* Drug: Cyclophosphamide
* Drug: Velcade®
* Drug: Dexaméthasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients newly diagnosed with symptomatic Multiple Myeloma (MM) patient - 18 ≤ age < 66 years - Eastern Cooperative Oncology Group Performance Status of 0, 1 or 2 - Patients must be eligible for Autologous Stem Cell Transplantation - Patients must have measurable disease by serum M-protein ≥ 10 g/L and/or urine M-protein ≥200mg/day - Female patients of child-bearing potential (FCBP): Must agree to have medically supervised pregnancy tests prior to starting study and every 21 days, including 4 weeks after the end of study treatment. This applies even if the patient practices complete and continued sexual abstinence. Must agree to use and be able to comply with effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including during periods of dose interruptions), and for 28 days after discontinuation of study therapy. - Male Patients: Must agree to use a condom during sexual contact with a FCBP, throughout study drug therapy, during any dose interruption and for one week after discontinuation of study therapy Must agree to not donate semen during study drug therapy and for one week after discontinuation of study therapy - All patients must: Agree to abstain from donating blood while taking study drug therapy and for one week after discontinuation of study drug therapy Agree not to share study medication with another person. - Patients must be capable of giving informed consent - Patients must be affiliated with French social security system Exclusion Criteria: - Asymptomatic Multiple myeloma - Non-secretory Multiple myeloma - Proven AL-amyloidosis - Age ≥ 66 years old - Prior or current systemic therapy for Multiple myeloma, including steroids (except for emergency use of a 4-day block of dexamethasone before randomization, maximum total dose allowed 160 mg) - Radiation therapy in the 2 weeks preceding randomization - National Cancer Institute grade ≥ 2 peripheral neuropathy - Haemoglobin < 8g/dL - Absolute neutrophil count < 1,000 cells / µL, platelet count < 50,000 cells / µL - Creatinine level > 170 µmol/L or requiring dialysis. - Bilirubin, transaminases or GamaGT > 3 UNL (upper normal limit) - Positive HIV serology, evidence of active Hepatitis B and C infection - Severe active infection - Inability to comply with an anti-thrombotic treatment regimen - A personal medical history of severe psychiatric disease - Uncontrolled diabetes contraindicating the use of high-dose dexamethasone - Non-controlled or severe cardiovascular disease (including a myocardial infarction in the 6 months prior to recruitment) - A personal medical history of cancer unless the patient has been without relapse after treatment discontinuation > or = 5 years (except for basocellular skin cancer or in situ cervical cancer) - Use of any investigational drug in the 30 days preceding randomization 22 - Pregnant or lactating women. 23 - Adults under juridical protection 24 - Known or suspected hypersensitivity to any of the study therapies or excipients 25 - Necessity of vaccination for yellow fever or with any other live vaccines

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: VELCADE (BORTEZOMIB) THALIDOMIDE DEXAMETHASONE (VTD)<br>Arm A: Induction therapy 4 cycles of VTD (21 days) Thalidomide® 100 mg/day Per Os Day1 to Day21 Velcade® 1.3 mg/m²/day Subcutaneous Day1, 4, 8 and 11 Dexamethasone 40 mg/day Per Os Day 1 to 4 and Day 9 to 12 Systematic stem cell harvest after cycle 3 Mobilization: Cyclophosphamide and one week after the last dose of Thalidomide, stem cells have to be harvested | Drug: Thalidomide®<br> <br> Drug: Velcade®<br> <br> Drug: Dexaméthasone<br> <br> |
| Active Comparator: VELCADE (BORTEZOMIB) CYCLOPHOSPHAMIDE DEXAMETHASONE (VCD)<br>For arm B: Induction therapy : 4 cycles of VCD (21 days) Cyclophosphamide 500 mg/m²/day, Per Os Day 1, 8, 15 Velcade® and Dexamethasone identical treatment to Arm A Systematic stem cell harvest after cycle 3 Mobilization: Cyclophosphamide and two weeks after the last dose of Cyclophosphamide, stem cells have to be harvested | Drug: Cyclophosphamide<br> <br> Drug: Velcade®<br> <br> Drug: Dexaméthasone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response assessment according to the criteria IMWG | compare the Response assessment in both arms: the Very good partial remission rate (according to the criteria IMWG) achieved with four courses of VTD with that achieved with four courses of VCD | 15-17 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response assessment according to the criteria IMWG | compare the Response assessment in both arms: the following parameters after induction treatment with four courses of VTD or four courses of VCD the Complete remission rate (according to the criteria IMWG) | 15 - 17 month | 
| Number of Adverse Events | To evaluate the Safety of induction therapy | 15-17 month | 
| Number of collected stem cell |  | 17 month | 
| Number of death | To evaluate Overall and Progression-Free Survival | 17 month | 
| Response assessment according to the criteria IMWG | compare the Response assessment in both arms: Compare the following parameters after induction treatment with four courses of VTD or four courses of VCD the Partial remission rate (according to the criteria IMWG) | 15-17 month | 
| Number of relapse according to the criteria IMWG | Progression-Free Survival | 17 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple myeloma, Newly Diagnosed