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

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

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: January 2007

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

Intervention(s) in this Clinical Trial

• 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)

Primary Measures

• Determinate the efficacy of combination velcade, melphalan, prednisone
  • Time Frame: 1 year
    Safety Issue?: No

Secondary Measures

• Assess safety and tolerability
  • Time Frame: 1 year
    Safety Issue?: Yes
• Assess potential superiority of this regimen versus historical controls with melphalan and prednisone alone
  • Time Frame: 2 years
    Safety Issue?: No
• Evaluate efficacy in terms of progression-free survival and overall survival
  • Time Frame: 5 years
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 65 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: PETHEMA Foundation

Overall Clinical Trial Officials and Contacts

San Miguel Jesús, Professor Study Chair Hospital Clinico Universitario de Salamanca  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00388635

Study ID Number: PET-VEL-2004-01

ClinicalTrials.gov Identifier: NCT00388635

Health Authority: Spain: Ministry of Health

Pethema Foundation web

Spanish association of Haematology