Combination Chemotherapy With or Without PSC 833 in Treating Patients With Relapsed or Refractory Multiple Myeloma
Condition: Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so
      they stop growing or die. Some tumors become resistant to chemotherapy drugs. Combining PSC
      833 with chemotherapy may reduce resistance to the drug, and allow more tumor cells to be
      killed. It is not yet known whether combination chemotherapy plus PSC 833 is more effective
      than combination chemotherapy alone in treating patients with relapsed or refractory multiple
      myeloma.

      PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy
      with or without PSC 833 in treating patients with relapsed or refractory multiple myeloma.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the overall survival and objective response rate of patients with relapsed or
           refractory multiple myeloma treated with vincristine, doxorubicin, and dexamethasone
           (VAD) with or without PSC 833.

        -  Compare event free survival and subjective response in patients treated with these
           regimens.

        -  Correlate treatment outcome with p-glycoprotein expression.

        -  Determine whether prognostic factors previously determined to be useful in untreated
           patients (i.e., plasma cell labeling index and multidrug resistance determined from bone
           marrow aspirates, serum beta 2-microglobulin and interleukin-6 receptor levels)
           correlate with objective and subjective response and event-free and overall survival in
           patients treated with these regimens.

        -  Compare the toxicity of VAD with or without PSC 833.

      OUTLINE: This is a randomized, multicenter study. Patients are stratified by response to
      prior treatment, prior doxorubicin and/or vincristine, prior autologous peripheral blood stem
      cell transplantation, and center.

      Patients are randomized to 1 of 2 treatment arms:

        -  Arm I: The first group receives vincristine, doxorubicin, and dexamethasone (VAD).
           Patients receive higher dose vincristine IV over 96 hours and higher dose doxorubicin IV
           over 96 hours on days 1-4 and oral dexamethasone daily on days 1-4 and 15-18.

        -  Arm II: The second group receives VAD plus oral PSC 833. Patients receive oral PSC 833
           every 6 hours beginning on day 1 and continuing for 20 doses. Patients receive lower
           dose vincristine IV over 96 hours and lower dose doxorubicin IV over 96 hours on days
           2-5 and oral dexamethasone daily on days 2-5 and 16-19.

      Treatment in both arms repeats every 4 weeks in the absence of disease progression or
      unacceptable toxicity. After completion of 2 courses, patients are reevaluated, and those
      with stable or responding disease continue treatment for 2 courses beyond maximum response.
      Doxorubicin is discontinued in patients who receive a maximum lifetime dose but still have
      stable or responding disease.

      Patients are followed every 2 months for survival.

      PROJECTED ACCRUAL: A total of 360 patients will be accrued for this study over approximately
      20 months.
    

Intervention name(s): dexamethasone; doxorubicin hydrochloride; valspodar; vincristine sulfate
Intervention type(s): Drug; Drug; Drug; Drug
Intervention MeSH terms: Dexamethasone; Doxorubicin; Liposomal doxorubicin; Vincristine
Allocation: Randomized
Primary purpose: Treatment
Keywords: refractory multiple myeloma