Tandem Transplantation in Multiple Myeloma (MM) Patients With <12 Months of Prior Treatment
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      The two objectives of this study are:

        -  To increase the 2-year event-free survival from 55%, established with Total Therapy II
           (UARK 98-026), to 75% in myeloma patients with cytogenetic abnormalities, and from 80%,
           established with the Total Therapy II regimen, to 95% in myeloma patients without
           cytogenetic abnormalities.

        -  To determine whether bortezomib, thalidomide, and dexamethasone can be safely
           incorporated with transplant 1 into the established pre-transplant regimen of high-dose
           melphalan (used in Total Therapy II) and whether Velcade and gemcitabine can be safely
           added to the transplant 2 high-dose chemotherapy regimen of combination melphalan and
           BCNU.
    

Detailed description: 
      This study is targeted towards patients who have been diagnosed with Multiple Myeloma and
      have had no prior autologous or allogeneic transplant. Furthermore, only up to 12 months of
      prior treatment are allowed in this patient population. The study schema consists of one
      round of induction chemotherapy, two transplants, one round of consolidation chemotherapy,
      and two years of maintenance treatment. This study design differs from its historical
      predecessors in the following manner:

        -  In contrast to Total Therapy II and III, which only allow enrollment of patients with at
           most one cycle or one month of treatment prior to enrollment, the proposed study allows
           enrollment of patients with up to 12 months of prior treatment. No statistically
           significant difference in outcome between patients with one or no cycle of preceding
           therapy and those with up to 12 months of prior therapy. This should allow enrollment of
           significantly more myeloma patients.

        -  Induction therapy has been reduced to a single cycle.

        -  Bortezomib and thalidomide have been added to the transplant regimen.

        -  BCNU is added to the second transplant to high dose melphalan.

        -  Gemcitabine is added to the second transplant regimen.

        -  Consolidation treatment has been reduced to a single cycle.

        -  The first year of maintenance is with bortezomib, thalidomide and dexamethasone, and the
           second year of maintenance therapy consists of dexamethasone only.

        -  The novel agents thalidomide and bortezomib are not introduced upfront, but only with
           transplantation and maintenance.
    

Intervention name(s): tandem autologous transplantation
Intervention type(s): Combination Product
Intervention description(s): DPACE: dexamethasone 20 mg days 1-4 and 8-11, cisplatin 10 mg/m2 days 1-4, Adriamycin 10 mg/m2 days 1-4, cyclophosphamide 400 mg/m2 days 1-4, etoposide 40 mg/m2 days 1-4.
Transplant 1: Dexamethasone 20 mg days -4 to -1 and +2 to +5. Velcade 1mg/m2 on days -4,-1, +2, and +5. Thalidomide 100mg on day -4 to day +5. Melphalan, 100 mg/m2 on days -4 and -1.
Transplant 2: Dexamethasone 20 mg on days -4 to -1 and +2 to +5. BCNU 300mg/m2 on day -4. Melphalan 140 mg/m2 on day -1. Velcade 1mg/m2 on days -4, -1, +2, +5. Gemcitabine 1000 mg/m2 on days -4 + -1.
Maintenance year 1: Bortezomib 1.0 mg/m2 on days 1, 4, 15,18 every cycle. Thalidomide, 100 mg . Dexamethasone,20 mg,on days 1-4 & 15-18 every cycle.
Maintenance year 2: Dexamethasone, 20 mg,days 1-4 every cycle.
Intervention model: Single Group Assignment
Intervention model description: Induction- Tandem Transplants with VTD-MEL and gemcitabine, BCNU, melphalan, velcade and dexamethasone- Maintenance therapy
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Multiple Myeloma; myeloma