Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Chronic Myelogenous or Acute Leukemia
Condition: Leukemia
MeSH terms: Leukemia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation
      may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

      PURPOSE: Phase I/II trial to study the effectiveness of high-dose chemotherapy plus
      peripheral stem cell transplantation in treating patients with chronic myelogenous or acute
      leukemia.
    

Detailed description: 
      OBJECTIVES: I. Determine the maximum tolerated dose of decitabine in combination with
      busulfan and cyclophosphamide in patients with hematologic malignancies. II. Establish the
      pharmacokinetics of decitabine and busulfan in this patient population. III. Determine the
      effectiveness of this combination in achieving durable complete remission in patients with
      chronic myelogenous leukemia (CML) in blast crisis or acute myelogenous leukemia (AML) in
      relapse undergoing allogeneic stem cell transplantation.

      OUTLINE: In cohorts of 3, patients receive escalating doses of decitabine (DAC) IV over 4
      hours on days -8 and -7. Busulfan is administered orally every 6 hours on consecutive days -6
      through -4. Cyclophosphamide is given by vein (IV) over 1 hour on consecutive days -3 and -2.
      The maximum tolerated dose of DAC is defined as the dose at which 2 patients experience dose
      limiting toxicity. Donors receive filgrastim subcutaneously (SQ) daily every 12 hours
      starting 2-4 days prior to the first stem cell collection and before DAC infusion.
      Leukapheresis is conducted daily. If insufficient number of cells are collected, blood marrow
      is harvested for supplementation. Stem cells are infused on day 0. For graft vs host disease
      prophylaxis (GVHD), patients receive tacrolimus IV beginning one day before stem cell
      infusion, then orally following tolerance to tacrolimus. Patients intolerant to tacrolimus
      receive cyclosporine IV beginning on day -2, then orally following tolerance and engraftment.
      All patients receive methylprednisolone given according to clinical grade of GVHD procedures.
      For CNS prophylaxis, methotrexate is given intrathecally or intraventricularly monthly,
      beginning on the second month through the eighth month of treatment. Allogeneic patients are
      followed until the end of 1 year.

      PROJECTED ACCRUAL: An estimated 30 allogeneic recipients will be recruited in 2 years for the
      expected study duration of 2-3 years.
    

Intervention name(s): Filgrastim; Busulfan; Cyclophosphamide; Cyclosporine; Decitabine (DAC); Methotrexate; Methylprednisolone; Tacrolimus; Allogeneic Bone Marrow Transplantation; Peripheral Blood Stem Cell Transplantation
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Procedure
Intervention description(s): Subcutaneously (SQ) daily every 12 hours starting 2-4 days prior to the first stem cell collection and before DAC infusion.; Administered orally every 6 hours on consecutive days -6 through -4.; Given intravenously (IV) over 1 hour on consecutive days -3 and -2.; Patients intolerant to tacrolimus receive cyclosporine IV beginning on day -2, then orally following tolerance and engraftment.; IV over 4 hours on days -8 and -7.; Given intrathecally or intraventricularly monthly, beginning on the second month through the eighth month of treatment.; Given according to clinical grade of GVHD procedures.; IV beginning one day before stem cell infusion, then orally following tolerance to tacrolimus.; Infusion of stem cells on Day 0.; Stem cell infusion on Day 0.
Other intervention name(s): C-CSF; Neupogen; Busulfex; Myleran; Cytoxan; Neosar; Sandimmune; CYA; Cyclosporin A; Dacogen; Depo-Medrol; Medrol; Solu-Medrol; Prograf; ABMT; PBSCT
Intervention MeSH terms: Cyclosporine; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cyclophosphamide; Busulfan; Methotrexate; Decitabine; Tacrolimus; Cyclosporins; Prednisolone hemisuccinate; Prednisolone phosphate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent adult acute myeloid leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia