Treatment of Primary Plasma Cell Leukaemia in Subjects Under the Age of 70
Condition: Multiple Myeloma
MeSH terms: Leukemia; Multiple Myeloma; Leukemia, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      Plasma cell leukaemia is a rare variety of multiple myeloma with a poor prognosis. Plasma
      cell leukaemia is defined as: at least 2,000 circulating plasma cells per µL for a blood
      leukocyte count higher than 10,000/µL or 20% of plasma cells for a leukocyte count less than
      10,000/µL. Plasma cell leukaemia can be either primary, when it constitutes the first
      manifestation of the disease, or secondary in the setting of relapsed/refractory multiple
      myeloma. Primary plasma cell leukaemia (PPL) is a rare disease, representing only 1 to 2% of
      all cases of multiple myelomas at diagnosis. As the annual incidence of multiple myeloma in
      France is about 4,000 new cases, an estimated 40 to 80 new cases of PPL would be observed
      each year.

      Few data are currently available in the literature concerning the pathophysiology and
      therapeutic management of PPL, and are derived from retrospective series based small numbers
      of patients. The prognosis of PPL in response to conventional chemotherapy remains poor with
      a median survival of 7 to 14 months. However, longer survivals have been obtained with
      intensive therapy and haematopoietic stem cell transplantation (allogeneic or autologous
      HSCT).

      The investigators propose to perform a prospective study of the management of patients with
      PPL under the age of 70 years, in combination with a laboratory study: 12 weeks of induction
      chemotherapy by liposomal Bortezomib-Dexamethasone-Doxorubicin (PAD) alternating with
      Bortezomib-Dexamethasone-Cyclophosphamide (VCD) for a total of 4 cycles. Peripheral blood
      stem cell collection after mobilization by G-CSF will be performed after high-dose
      Cyclophosphamide chemotherapy. Autologous HSCT conditioned by high-dose Melphalan will be
      performed during the following month for all responding patients. During the 3 months after
      this first autologous HSCT, allogeneic HSCT with attenuated conditioning will be proposed in
      patients under the age of 66 years in complete remission with a suitable donor, and another
      systematic autologous HSCT will be proposed in all other patients. For all patients not
      treated by allogeneic HSCT, consolidation/maintenance therapy will be performed 3 months
      after the second autologous HSCT: 4 quarterly consolidations with
      Bortezomib-Lenalidomide-Dexamethasone (VRD) with maintenance by 2 months of Lenalidomide
      between these cycles, for a total duration of one year.

      The laboratory assessment will consist of blood and bone marrow samples systematically
      obtained at diagnosis for plasma cell phenotyping by cytometry, cytogenetics, FISH, study of
      the gene expression profile and SNParray. A DNA bank and plasma bank will be constituted. The
      investigators also propose to study residual disease by cytometry (after the first autologous
      HSCT, before and at the end of the consolidation/maintenance phase), as it increasingly
      appears to have a major impact on survival in multiple myeloma.
    


Intervention name(s): PAD-VCD
Intervention type(s): Drug
Intervention description(s): 12 weeks of induction chemotherapy by liposomal Bortezomib-Dexamethasone-Doxorubicin (PAD) alternating with Bortezomib-Dexamethasone-Cyclophosphamide (VCD) for a total of 4 cycles
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: primary plasma cell leukaemia; treatment