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

This study has been completed.
Sponsor:
Collaborators:
Millennium Pharmaceuticals, Inc.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by:
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT00388635
First received: October 16, 2006
Last updated: January 8, 2011
Last verified: January 2011
  Purpose

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


Condition Intervention Phase
Multiple Myeloma
Drug: Velcade
Drug: Melphalan
Drug: Prednisone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • Determinate the efficacy of combination velcade, melphalan, prednisone [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess safety and tolerability [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Assess potential superiority of this regimen versus historical controls with melphalan and prednisone alone [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Evaluate efficacy in terms of progression-free survival and overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: April 2004
Study Completion Date: December 2008
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    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)
Detailed Description:

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

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00388635

Locations
Spain
Hospital Central de Asturias
Oviedo, Asturias, Spain
Hospital Universitario de Canarias
Tenerife, Islas Canarias, Spain
Hospital Son Llatzer
Palma de Mallorca, Mallorca, Spain
Clínica Universitaria de Navarra
Pamplona, Navarra, Spain
Hospital Clínic
Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Germans Trias i Pujol
Barcelona, Spain
Hospital Virgen Blanca de León
Leon, Spain
Hospital Clínico San Carlos de Madrid
Madrid, Spain
Hospital Doce de Octubre
Madrid, Spain
Hospital Ramón y Cajal
Madrid, Spain
Hospital Universitario de la Princesa
Madrid, Spain
Hospital Morales Messeguer
Murcia, Spain
Hospital Clínico Universitario de Salamanca
Salamanca, Spain
Hospital General de Segovia
Segovia, Spain
Hospital La Fe
Valencia, Spain
Hospital Universitario Dr. Peset
Valencia, Spain
Hospital Clínic
Valencia, Spain
Hospital Clínico Lozano Blesa
Zaragoza, Spain
Sponsors and Collaborators
PETHEMA Foundation
Millennium Pharmaceuticals, Inc.
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Chair: San Miguel Jesús, Professor Hospital Clinico Universitario de Salamanca
  More Information

Additional Information:
Publications:
1. Greenlee RT, Murray T, Bolden S , Wingo PA. Cancer Statistics, 2000. CA Cancer J Clin 2000; 50: 7-33.
2. Longo D. Plasma cell disorders. In : Fauce A, et al. Ed. Harrison's Principles of Internal Medicine. 14th Ed. New York, New York: Mc Graw-Hill; 1998: 712-718
7. Smith ML, Newland AC. Treatment of myeloma. QJM 1999 ;92(1) :11-14.
8. Bataille r, Harousseau JL. Multiple Myeloma. N Eng J Med 1997; 336(23):1657-1664.
9. Alexanian R, Dimopoulos M. Drug therapy: the treatment of multiple myeloma. N Eng J Med 1994;330(7):484-489.
19. Sherr CJ. Cancer cell cyecles. Science 1996;274:1672-1677

Responsible Party: pethema
ClinicalTrials.gov Identifier: NCT00388635     History of Changes
Other Study ID Numbers: PET-VEL-2004-01
Study First Received: October 16, 2006
Last Updated: January 8, 2011
Health Authority: Spain: Ministry of Health

Keywords provided by PETHEMA Foundation:
Multiple Myeloma
Patients over 65 years old

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Prednisone
Bortezomib
Melphalan
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 16, 2014