Velcade-Melphalan-Prednisone in Older Untreated Multiple Myeloma Patients.

Study Overview
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Brief Summary
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This protocol is planned as a multicentric, national, open-label trial designed to evaluate, first, optimal dose of Velcade® (Bortezomib) in combination with melphalan and prednisone. After optimal dose is known, the second aim is evaluate safety and tolerance of V-MP plan, in respond terms, in a cohort of 60 patients. Finally, the entire results will be compared with those obtained from a series of 100 patients, all of them over 70 years old, diagnosed of Multiple Myeloma belonging to the GEM protocol finished in May 2003

Detailed Description
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Multiple Myeloma is a neoplastic disorder of the last maturation stage of B cell, called plasmatic cell. It represents the second most common haematological neoplasia, after Non Hodgkin Lymphoma. The annual incidence is over 4 cases per 100.000. Multiple Myeloma is an invariably mortal disease. When illness advances, the reduction of infections resistance, the intense bones destruction (with bone pain, pathological fractures and hypercalcemia), anaemia, renal failure and, in a less frequency, neurological complications and hyperviscosity provoke severe morbidity and mortality. Five-year survival rate in patients with Multiple Myeloma treated with conventional chemotherapy is 29%. There is an urgent need of new therapeutic agents for the treatment of this disease

Official Title
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A National, Multi-Center, Open-Label Study of Velcade in Combination With Melphalan and Prednisone (V-MP) in Older Untreated Multiple Myeloma Patients.

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Velcade
* Drug: Melphalan
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements. Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. Age over 65 years. Patient recently diagnosed with symptomatic Multiple Myeloma based on standard criteria and that has not received any previous chemotherapy treatment for Multiple Myeloma. Patient has measurable disease, defined as follows: For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value and, where applicable, urine light-chain excretion of ≥ 200 mg/24 hours. For oligo or non-secretory multiple myeloma, measurable disease is defined by the presence of soft tissue (not bone) plasmacytomas as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan). In patients with oligo-secretory multiple myeloma, the serum and/or urine M-protein measurements are very low and difficult to follow for response assessment. In patients with non-secretory multiple myeloma, there is no M-protein in serum or urine. Patient has a Karnofsky performance status higher 60%. Patient has a life-expectancy >3 months. Patient has the following laboratory values within 14 days before Baseline visit (Day 1 of Cycle 1, before study drug administration: Platelet count ≥ 100x109/L, hemoglobin ≥ 8 g/dl and absolute neutrophil count (ANC) ≥ 1.0x109/L. Corrected serum calcium < 14mg/dl. Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal. Alanine transaminase (ALT): ): ≤ 2.5 x the upper limit of normal. Total bilirubin: ≤1.5 x the upper limit of normal. Serum creatinine value ≤ 2mg/dl. Exclusion Criteria: Patient previously received treatment with Velcade. Patient previously received treatment for Multiple Myeloma. Patient had major surgery within 4 weeks before enrollment. Patient has a platelet count < 100 x 109/L within 14 days before enrollment. Patient has an absolute neutrophil count < 1.0 x 109/L within 14 days before. Patient has < Grade 2 peripheral neuropathy within 14 days before enrollment. Patient has hypersensitivity to bortezomib, boron or mannitol. Patient has received other investigational drugs within 14 days before enrollment. Patient is known to be seropositive for the human immunodeficiency virus (HIV), Hepatitis B surface antigen-positive or active hepatitis C infection. Patient had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Patient is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.

Ages Eligible for Study
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Minimum 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Velcade|Phase I: Velcade, 1.0mg/m2-1.3mg/m2 in escalating doses every 6 weeks for 4 cycles Pase II: Velcade at optimal doses, twice a week (days 1, 4, 8, 11, 22, 25, 28 and 32) follow a rest period for 10 days (days 33 to 42)|
|Drug: Melphalan|Melfalán 9mg/m2 days 1 to 4, V.O, follow by a rest period of 38 days in phse I and II|
|Drug: Prednisone|Prednisone 60mg/m2 v.o days 1 to 4 follows by a rest period of 38 days (phase I and II)|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determinate the efficacy of combination velcade, melphalan, prednisone |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess safety and tolerability |  | 1 year | 
| Assess potential superiority of this regimen versus historical controls with melphalan and prednisone alone |  | 2 years | 
| Evaluate efficacy in terms of progression-free survival and overall survival |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, Patients over 65 years old