MINIALO-VELCADE2005: A Study of Bortezomib (Velcade) Treated Multiple Myeloma Patients Pre and Post Allogeneic Haematopoietic Progenitor Cell Transplant With no Myeloablative Conditioning (MINIALO-VELCAD)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||MINIALO-VELCADE2005: A Phase II National, Open-label, Multicenter, no Controlled Study of Treated With Bortezomib (Velcade) Multiple Myeloma Patients Pre and Post Allogeneic Haematopoietic Progenitor Cell Transplant With no Myeloablative Conditioning|
- Analyze the efficacy of allogeneic bone marrow transplantation in a reduced-intensity manner combined with bortezomib [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2007|
|Study Completion Date:||October 2014|
|Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
- 2 cycles of 21 days : Velcade days: 1, 4, 8 and 11
- 1 cycle of 13 days : Velcade days 1, 4, 8 and 11
- 2 cycles of 21 days : Velcade days 1, 8 and 15
- 5 cycles of 56 days : Velcade days 1, 8 and 15
- Day -2: Velcade
- 2 cycles of 21 days : Dexamethasone: days 1-4 and 8-11
- Days -9 al -5: Fludarabine
- Days -4 and -3: Melphalan.
Multiple Myeloma is a plasma cell disorder characterized by an uncontrolled proliferation of bone marrow plasma cells leading to skeletal destruction with bone pain, anemia, renal failure, hypercalcemia, recurrent bacterial infections and extramedullary plasmacytomas. It accounts for 1% of all malignancies and slightly more than 10% of hematologic malignancies, with an annual incidence of about four per 100.000. Although this disease is incurable with a median survival of about 3 years, remarkable treatment advances have been recently made, including high-dose therapy followed by stem cell rescue and, particularly, the introduction of novel promising agents with new mechanisms of action.
The treatment with alquilant agents, melphalan or cyclophosphamide combined with prednisone has a median of no more than 3 years survival rate in approximately 50%. The chemotherapy combination and high-dose dexamethasone increases response rate with minimal effects in survival benefit. The limited efficacy of conventional treatment produced the introduction of the high-dose therapy followed by a stem cells transplant in order to increase antitumoral effect and prolong disease-free overall survival.
This way, autologous stem cells transplant has turned into optimal treatment for patients younger than 65 years with myeloma. Nevertheless there is increasing evidence that it benefits only patients who showed complete disease remission after transplantation.
The transcendental factor that determines the CR post-transplantation achievement is the initial chemotherapy- sensitivity disease, measuring the rapidity and the grade of response (rapidity of maximum response assessment) and the pre-transplantation M protein level (i.e., the grade of response to the initial treatment).
On the other hand, the treatments with alquilant agents can impede the obtention of adequate numbers of stem cells that make impossible the autotransplantation practice. For this reason nowadays the treatments based on dexamethasone are used as initial chemotherapy.
However, these regimens and particularly AVD have less activity than alquilant agents treatment. Bortezomib has shown a fast antimyeloma activity (response after 1 or 2 cycles) in refractory patients, where myelosuppression and cellular injury are not observed.
Alternating bortezomib and dexamethasone as pre-transplant induction regimen would show the following advantages:
- a rapid and high effect raised by means of the use of two drugs with proven activity when they are administered separately,
- absence of stem cells injury,
- different toxicity types avoiding the habitual side effects because of the dexamethasone abuse, when this one is administered in every cycle as it happens in AVD type regimens.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00564200
|H. Clinic I Provincial|
|H. de la Santa Creu I Sant Pau|
|Instituto Catalán de Oncología|
|H. de Jerez|
|Jerez de la Frontera, Spain|
|H. 12 de Octubre|
|H. Univ. Gregorio Marañón|
|H. Univ. La Princesa|
|H. Univ. Morales Meseguer|
|H. Univ. Son Dureta|
|Palma de Mallorca, Spain|
|H. Univ. de Salamanca|
|Study Chair:||Bladé Joan, Dr||Hospital Clinic of Barcelona|