Comparison of Biological Therapies Following Combination Chemotherapy and Bone Marrow or Peripheral Stem Cell Transplantation in Women With Stage II or Stage III Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
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. Combining chemotherapy with peripheral stem cell transplantation or
      bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs
      and kill more tumor cells. Biological therapy may interfere with the growth of the cancer
      cells. It is not yet known which post-transplant biological therapy regimen is more effective
      for breast cancer.

      PURPOSE: Randomized phase III trial to compare the effectiveness of cyclosporine and
      interferon gamma to that of interleukin-2 following combination chemotherapy and bone marrow
      or peripheral stem cell transplantation in women who have stage II or stage III breast
      cancer.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the response, disease-free survival (DFS), and overall survival of women with
           high-risk stage II or III breast cancer treated with high-dose cyclophosphamide,
           thiotepa, and carboplatin with autologous marrow and/or peripheral blood stem cell
           transplantation.

        -  Determine the safety of immunomodulation consisting of cyclosporine and interferon gamma
           versus low-dose interleukin-2 in this patient population.

        -  Determine parameters associated with immune activation and autologous graft-versus-host
           disease.

        -  Determine which immunomodulation regimen is more efficacious with respect to DSF.

      OUTLINE: This is a randomized study. Patients are stratified according to stage (II vs III),
      age, lymph node status, and inflammatory histology. Patients are randomized to one of two
      immunomodulation arms.

      Autologous harvest of at least 1 million CD34+ cells /kg or 400 million mononuclear cells/kg
      must be achieved.

      All patients receive cyclophosphamide IV continuously and thiotepa IV continuously over 96
      hours on days -6 through -3 and carboplatin IV over 5 hours daily on days -6 through -3.
      Patients undergo autologous bone marrow and/or peripheral blood stem cell transfusion on day
      0.

        -  Arm I: Patients receive cyclosporine IV over 4 hours twice a day, beginning on day 0 and
           continuing until discharge from the hospital, and interferon gamma subcutaneously (SC)
           every 2 days on days 7-28.

        -  Arm II: Patients receive interleukin-2 SC daily for 28 days following recovery of blood
           counts.

      Treatment continues in the absence of disease progression or unacceptable toxicity.

      Patients are followed every 3 months for 1 year and then annually for 5 years.

      PROJECTED ACCRUAL: A total of 70 patients (30 with stage II disease and 40 with stage III
      disease) will be accrued over 2 years.
    

Intervention name(s): aldesleukin; recombinant interferon gamma; carboplatin; cyclophosphamide; cyclosporine; thiotepa; autologous bone marrow transplantation; peripheral blood stem cell transplantation
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Procedure; Procedure
Intervention MeSH terms: Interferons; Aldesleukin; Interferon-gamma; Cyclosporine; Cyclophosphamide; Thiotepa; Carboplatin; Cyclosporins
Allocation: Randomized
Primary purpose: Treatment
Keywords: stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer