High-Dose Sequential Therapy and Single Autologous Transplantation for Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      This study uses a sequence of high-dose chemotherapy drugs and a stem cell transplant to
      treat multiple myeloma. The study is being performed to evaluate the efficacy and side
      effects of treatment. Specifically, the study is designed to reduce the risk of interstitial
      pneumonitis.
    

Detailed description: 
      Analysis of 196 previously treated patients demonstrated a median event-free survival (EFS)
      of 36 months with a median overall survival of more than 6 years. The main toxicity of this
      therapy is related to carmustine-induced pneumonitis or interstitial pneumonitis (IP). This
      complication is related to the dose of carmustine. Institutional experience in myeloma
      patients using this dose of carmustine indicates an incidence of IP of34%.

      There have been recent studies evaluating the role of tandem autologous transplants for
      patients with multiple myeloma. These trials were based upon the hypothesis that performing
      tandem high-dose therapy regimens would lead to increased tumor cell kill, decreased tumor
      burden and an improvement in overall survival. Our results with high-dose sequential therapy
      including the dose-intense carmustine/melphalan transplant demonstrates similar median EFS
      and overall survival (OS) when compared with the results of tandem transplant approaches.The
      proposed trial will continue to use a high-dose sequential transplant approach, however, we
      will use a reduced dose of carmustine which we expect to be associated with a lower incidence
      of IP.
    

Intervention name(s): Cyclophosphamide; Etoposide; Melphalan; Carmustine; Filgrastim
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): Cyclophosphamide as a white powder in 100 mg, 200 mg and 500 mg vials, to be dissolved in ~250 mL of saline or D5W and infused IV over 2 hours; 100 mg etoposide as 5 mL solution in clear ampules for injection.; Melphalan as single-use glass vials of freeze-dried melphalan hydrochloride (equivalent to 50 mg of melphalan), to be reconstituted in 0.9% sodium chloride solution to not greater than 0.45 mg/mL, and administered within 1 hour of constitution.; Carmustine as a powder for reconstitution in 100 mg vials, to be reconstituted with 3 mL sterile dehydrated ethanol and D5W. Carmustine should be dissolved in 500 mL of 5% dextrose in water (D5W) and infused IV over 2 hours.; Filgrastim in vials of 300 µg or 480 µg at a concentration of 300 µg/mL, to be given as a daily subcutaneous injection.
Other intervention name(s): Cytoxan; Neosar; Etopophos; VePesid; Toposar; VP-16; Etoposide phosphate; Alkeran; L-PAM; L-Sarcolysin; Phenylalanine mustard; BiCNU; BCNU; Neupogen; Granulocyte-colony stimulating factor (G-CSF)
Intervention MeSH terms: Cyclophosphamide; Melphalan; Carmustine; Etoposide; Etoposide phosphate; Lenograstim
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment