• Number of patients with engraftment after induction chemotherapy [ Designated as safety issue: No ]
  

• Number and proportion of patients from whom ≥ 2 x 10e6 CD34-positive cells/kg are harvested [ Designated as safety issue: No ]
  
• Number and proportion of patients from whom ≥ 4 x 10e6 CD34-positive cells/kg are harvested [ Designated as safety issue: No ]
  
• CD34-positive cells/kg yield in each leukapheresis [ Designated as safety issue: No ]
  
• Number of leukaphereses to collect ≥ 2 x 10e6 CD34-positive cells/kg [ Designated as safety issue: No ]
  
• Number of leukaphereses to collect ≥ 4 x 10e6 CD34-positive cells/kg [ Designated as safety issue: No ]
  
• Proportion of patients with platelet recovery ≥ 20 x 10e9/L in the absence of transfusion for at least 7 days [ Designated as safety issue: No ]
  
• Proportion of patients with ANC recovery of ≥ 0.5 x 10e9/L [ Designated as safety issue: No ]
  
• Time to neutrophil recovery, defined as the time to neutrophil engraftment (i.e., ANC ≥ 0.5 x 10e9/L for 3 consecutive days) [ Designated as safety issue: No ]
  
• Time to ANC ≥ 1.0 x 10e9/L [ Designated as safety issue: No ]
  
• Time to platelet recovery, defined as the time to platelets ≥ 20 x 10e9/L in the absence of platelet transfusion support for at least 7 days [ Designated as safety issue: No ]
  
• Incidence and duration of hospitalization during mobilization phase and during post-transplantation phase [ Designated as safety issue: No ]
  
• Incidence and severity of adverse events during and after the use of pegfilgrastim 12 mg or pegfilgrastim 18 mg and filgrastim [ Designated as safety issue: Yes ]
  

OBJECTIVES:

Primary

• Compare engraftment of peripheral blood progenitor cells (PBPCs) mobilized by 2 different fixed doses of pegfilgrastim versus a by-weight dose of filgrastim (G-CSF).

Secondary

• Determine the ability of 2 different fixed doses of pegfilgrastim to mobilize PBPCs.
• Determine the safety of pegfilgrastim during PBPC mobilization and collection.
• Determine the effect of different induction chemotherapy regimens on autologous progenitor cell transplantation.

OUTLINE: This is a multicenter study. Patients are stratified by type of induction chemotherapy (Thal/Dex vs VAD vs Vel-Dex vs VTD) and by stage of disease according to International Prognostic Index criteria (stage I [i.e., beta-2 microglobulin < 3.5 and albumin > 35] vs stages II and III).

• Induction therapy: Patients receive 3-4 courses of 1 of the following regimens:

  • VAD: Patients receive vincristine, doxorubicin hydrochloride, and dexamethasone.
  • Thal/Dex: Patients receive thalidomide and dexamethasone.
  • Vel-Dex: Patients receive bortezomib and dexamethasone.
  • VTD: Patients receive bortezomib, thalidomide, and dexamethasone. Patients achieving complete, partial, or minimal response after 3-4 courses of induction therapy proceed to peripheral blood progenitor cell (PBPC) mobilization 17 days after completion of induction therapy.

• PBPC mobilization: Patients are randomized to 1 of 3 arms.

  • Arm I: Patients receive filgrastim subcutaneously (SC) once daily until the final leukapheresis.
  • Arm II: Patients receive a single dose of pegfilgrastim SC.
  • Arm III: Patients receive pegfilgrastim as in arm II at a higher dose.
• Leukapheresis: Patients undergo up to 3 leukaphereses to obtain adequate numbers of CD34-positive filgrastim- or pegfilgrastim-mobilized PBPCs for engraftment. Patients achieving a sufficient number of collected PBSCs proceed to conditioning chemotherapy.
• Conditioning chemotherapy: Patients receive high-dose melphalan* IV over 1-2 days. Patients then proceed to PBPC transplantation.

NOTE: *Patients ≥ 65 years old receive melphalan at a lower dose.

• Autologous PBPC transplantation: Patients undergo infusion of PBPCs on day 0. Patients in all arms receive G-CSF support beginning on day 1 after PBPC transplantation and continuing until blood counts recover for 3 consecutive days.

After completion of study therapy, patients are followed for up to 100 days post-transplantation.