A Multicenter Open Label Phase II Study of Pomalidomide and Cyclophosphamide and Dexamethasone in Relapse/Refractory Multiple Myeloma Patients Who Were First Treated Within the IFM/DFCI 2009 Trial
Condition: Multiple Myeloma; First Relapse
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Recurrence
Study type: Interventional
Phase: Phase 2

Summary: 
      Imnovid in combination with dexamethasone is indicated in the treatment of adult patients
      with relapsed and refractory multiple myeloma who have received at least two prior treatment
      regimens, including both lenalidomide (Revlimid) and bortezomib (Velcade), and have
      demonstrated disease progression on the last therapy.

      Patients with relapsed and refractory multiple myeloma who have received bortezomib,
      lenalidomide, dexamethasone combination, considered to be the multiple myeloma optimal
      treatment, can access to pomalidomide under marketing authorization only as from third line
      of treatment.

      In France this combination is not authorized for marketing for a first line treatment and
      only patient randomized in the IFM/DFCI 2009 trial received it.

      This study concerns patients previously randomized in the IFM/DFCI 2009 trial who have
      received bortezomib, lenalidomide and Dexamethasone combination in first line, which at
      progression/relapse time therapeutic opportunities remained limited and who cannot access
      pomalidomide under marketing authorization.

      This study is a multicentre, phase 2, open label, study testing the triple combination of
      pomalidomide and cyclophosphamide and dexamethasone (PCD) in multiple myeloma patients who
      are refractory or in first progression/relapse after a first line treatment with bortezomib
      and lenalidomide, an IMiDs (an Immuno Modulatory Drug and a proteasome inhibitor) according
      to the IFM/DFCI 2009 trial.

      In the IFM/DFCI trial, patients in arm A received eight cycles of the
      Velcade-Revlimid-Dexamethasone combination followed by 1 year of lenalidomide maintenance,
      patients in arm B received 3 cycles of Velcade-Revlimid-Dexamethasone combination plus
      melphalan 200mg/m2 with an autologous transplantation followed by 2 cycles of
      Velcade-Revlimid-Dexamethasone combination consolidation and 1 year of lenalidomide
      maintenance.

      This study will contain 3 treatment phases:

        -  Study treatment phase:

      All patients will receive 4 cycles (28 days) of pomalidomide-cyclophosphamide-dexamethasone
      combination.

        -  Consolidation phase (depends on the initial randomization in the IFM/DFCI 2009 trial):

             -  For patients previously randomized in IFM/DFCI 2009's arm A:

                  -  Melphalan 200 mg/m2 followed by Autologous Transplantation

                  -  Three months after, 2 cycles of pomalidomide-cyclophosphamide-dexamethasone
                     combination

             -  For patients previously randomized in IFM/DFCI 2009's arm B:

                  -  5 cycles of pomalidomide-cyclophosphamide-dexamethasone combination

        -  Maintenance phase (identical to all patients) subsequent cycles of pomalidomide and
           Dexamethasone until progression / relapse or discontinuation for any other reason.

      For arm B patients, in case relapse occurs at least 12 months after the end of the
      maintenance IFM/DFCI 2009 trial, they could proceed to a second autologous transplantation
      and therefore follow the arm A procedure. The decision to proceed to a second transplant will
      be made by the physician and the patient.

      In order to have the same amount of patients enrolled in this trial in the initial Arm A and
      Arm B of the IFM/DFCI 2009 trial, once 50 patients have been included in either arm A or B,
      subsequent patients will be eligible if they have not been initially treated as the first 50
      patients from either arm.

      The primary endpoint is the response rate (Partial Response (PR) or better) after 4 cycles of
      the triple combination pomalidomide and cyclophosphamide and dexamethasone (PCD) in the
      studied population using International Myeloma Working Group (IMWG) response criteria.
    


Intervention name(s): PCD; Autologous transplantation (ASCT)
Intervention type(s): Drug; Procedure
Intervention description(s): STUDY TREATMENT PHASE: All patients
4x 28 days cycles of PCD
[Pomalidomide: 4mg/day oral route on 21 days per cycle]
[Cyclophosphamide: 300mg/day oral route on days 1, 8, 15, 22 per cycle]
[Dexamethasone: 40mg/day oral route on days 1, 2, 3, 4 and 15, 16, 17, 18 per cycle]
CONSOLIDATION PHASE: depends on previous IFM/DFCI 2009's arm:
Arm A:
Melphalan 200mg/m2 followed by Autologous Transplantation
2x 28 days cycles of PCD, three months post transplantation
Arm B:
5x 28 days cycles of PCD
[Pomalidomide: 4mg/day oral route on 21 days per cycle]
[Cyclophosphamide: 300mg/day oral route on days 1, 8, 15, 22 per cycle]
[Dexamethasone: 40mg/day oral route on days 1, 8, 15, 22 per cycle]
MAINTENANCE PHASE: All patients
- Until progression/relapse or discontinuation for any other reason
[Pomalidomide: 4mg/day oral route on 21 days per cycle]
[Dexamethasone: 20mg/day oral route on days 1, 8, 15, 22 per cycle]; Arm A:
•Melphalan 200mg/m2 followed by Autologous Transplantation
Other intervention name(s): Pomalidomide-Cyclophosphamide-Dexamethasone association
Intervention MeSH terms: Dexamethasone; Cyclophosphamide; Pomalidomide
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Myeloma; Multiple Myeloma; Relapse; Refractory; PCD; IFM/DFCI 2009; Transplantation; Autologous; Pomalidomide; Immunoglobulin; Ig; Free light Chain