Sequential Trial on Reduced Intensity Conditioning (RIC) Allogeneic Transplantation
Condition: Hematologic Malignancies; Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms; Hematologic Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The aim of the current study is to improve the outcome of patients with hematologic
      malignancies (in a phase I trial) and more specifically multiple myeloma (in a phase II
      trial) by 2 interventions: reduce the risk of graft-versus-host disease (GVHD) and improve
      the efficacy of the procedure decreasing the risk of relapses after transplant.

      Currently, the standard approach used in most centers to prevent graft-versus-host disease
      after allogeneic transplantation is based on the combination of a calcineurin inhibitor
      (cyclosporine or tacrolimus) plus a short course of methotrexate. Unfortunately, this
      strategy is far from ideal, since the risk of acute GVHD is in the range of 30-40% among
      patients receiving a matched related donor transplantation and even higher among patients
      receiving transplantation from an unrelated donor while the incidence of chronic GVHD is
      60-70% among patients receiving peripheral blood progenitor cells from either a related or
      unrelated donor.

      As far as the patients with multiple myeloma (MM) is concerned, although the development of
      new drugs has markedly changed the outcome and management of these patients, allogeneic
      transplantation so far appears to be the only curative option, especially among those
      patients relapsing after first line treatment. Nevertheless, still new strategies within the
      allogeneic transplant setting are needed to improve its results.

      Relapses may occur either extramedullary (very common in this setting) or systemic. In order
      to reduce the risk of systemic relapses the investigators will use maintenance therapy with
      Lenalidomide (Len) which, together with bortezomib (Bz) should contribute to eradicate
      minimal residual disease (MRD). In case the patient do not obtain complete remission or near
      complete remission after transplant, in addition to the maintenance therapy, the
      investigators will use four intensification cycles with VRD (Bz-Len-Dexamethasone).

      In summary, the goal is to optimize the efficacy of allogeneic transplantation by two
      interventions: one focused on reducing the risk of relapse and the other on reducing the
      incidence of GVHD.
    


Intervention name(s): Bz (Bortezomib); Len (lenalidomide)
Intervention type(s): Drug; Drug
Intervention description(s): Bz 1.3 mg/m2 on days +1, +4 and +7. Maintenance therapy and dose reduction pre-specified.; Len at a dose of 6 mg po on day -5 and then 4 mg per day in order to maintain serum levels in the range of 6-12 ng /mL.
Maintenance therapy and dose reduction pre-specified.
Other intervention name(s): Codenamed PS-341; Marketed as Velcade; Rapamycin; CC-5013; Marketed as Revlimid
Intervention MeSH terms: Lenalidomide; Bortezomib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Allogeneic transplantation; Hematologic malignancies; Multiple myeloma; RIC (Reduced Intensity Conditioning)