MINIALO-VELCADE2005: A Study of Bortezomib (Velcade) Treated Multiple Myeloma Patients Pre and Post Allogeneic Haematopoietic Progenitor Cell Transplant With no Myeloablative Conditioning
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary objective of this study is to analyze the efficacy of allogeneic bone marrow
      transplantation in a reduced-intensity manner combined with bortezomib in the treatment of
      multiple myeloma with bad prognosis, in order to evaluate the response and relapse rates
    

Detailed description: 
      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:

        1. a rapid and high effect raised by means of the use of two drugs with proven activity
           when they are administered separately,

        2. absence of stem cells injury,

        3. 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.
    

Intervention name(s): Bortezomib; dexamethasone; Fludarabine; Melphalan
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): PREACONDICIONAMIENTO:
2 cycles of 21 days : Velcade days: 1, 4, 8 and 11
1 cycle of 13 days : Velcade days 1, 4, 8 and 11
ACONDICIONAMIENTO:
- Day -2: Velcade
POSTRANSPLANTATION:
2 cycles of 21 days : Velcade days 1, 8 and 15
5 cycles of 56 days : Velcade days 1, 8 and 15; PREACONDICIONAMIENTO:
- 2 cycles of 21 days : Dexamethasone: days 1-4 and 8-11; ACONDICIONAMIENTO:
- Days -9 al -5: Fludarabine; ACONDICIONAMIENTO:
- Days -4 and -3: Melphalan.
Intervention MeSH terms: Dexamethasone; Fludarabine; Bortezomib; Melphalan
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Multiple Myeloma, transplant