Carfilzomib, Cyclophosphamide, Dexamethasone in Transplant Eligible Newly Diagnosed High-risk Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      Patients with high risk multiple myeloma have shorter remission periods and reduced overall
      survival. Prognostic significance of minimal residual disease negative remission is being
      highlighted in many of the newer studies.

      The current phase 2 study investigates the combination of carfilzomib together with
      cyclophosphamide and dexamethasone in patients with high risk multiple myeloma in younger
      transplant-eligible patients.
    

Detailed description: 
      Carfilzomib is administered over 30 minutes as an infusion. For cycle 1 only, Carfilzomib is
      administered at 20mg/m2 IV on days 1 and 2, followed by escalation to 36 mg/m2 on days 8,9,15
      and 16 on a 28 day cycle. Patients who tolerate 36 mg/m2 dose are kept at this dose for the
      subsequent cycles on Days 1, 2, 8, 9, 15, 16 on a 28 day cycle. Dose and schedule
      modifications for intolerable side effects are detailed in the protocol. Additionally
      Cyclophosphamide is given a fixed dose of 500mg once per week orally, along with
      dexamethasone, given on the days of Carfilzomib administration, 30 minutes to 4 hours prior
      to Carfilzomib. Patients will undergo blood tests weekly and serum protein electrophoresis
      every 4 weeks during treatment. Within completion of 5 cycles of treatment, patients would
      undergo stem cell collection using chemotherapy and GCSF mobilization. After completion of 6
      cycles of treatment, autologous bone marrow transplantation will be performed. Three months
      following bone marrow transplantation, subjects will undergo further 2 consolidation cycles.
      After consolidation, subjects will undergo disease assessment by blood and subjects who are
      in CR will undergo bone marrow investigations and MRD analysis MPFC. Patients who achieve MRD
      negativity by MPFC will be managed expectantly by watch and wait. Patients who are MRD
      positive at this stage will receive maintenance for 2 years or till disease progression.
      Follow up would extend till a minimum of 2 years from completion of the study. At the end of
      2 years post maintenance or expectant monitoring, subjects who are in CR will undergo disease
      assessment by blood and bone marrow investigations and MRD analysis MPFC.
    

Intervention name(s): Carfilzomib, , Cyclophosphamide, Dexamethasone
Intervention type(s): Drug
Intervention description(s): Carfilzomib is administered intraveneously over 30 minutes. For cycle 1 only, Carfilzomib is administered at 20mg/m2 on Day 1 and 2, dose will be escalated to 36mg/m2 on Day 8,9,15 and 16 of the 28-days cycle. Patients who tolerate the 36mg/m2 dose are kept at this dose for the subsequent cycles on Day 1,2,8,9,15,16 on a 28 days cycle. Cyclophosphamide is given at a fixed dose of 500mg once per week orally, along with dexamethasone which is given on the days of Carfilzomib administration, 30 minutes to 4 hours prior to Carfilzomib infusion.
Other intervention name(s): Kyprolis
Intervention MeSH terms: Dexamethasone; Cyclophosphamide
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment