S0535, Gemtuzumab and Combination Chemotherapy in Treating Patients With Previously Untreated Acute Promyelocytic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Promyelocytic, Acute
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer
      cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies,
      such as gemtuzumab, can block cancer growth in different ways. Some find cancer cells and
      help kill them or carry cancer-killing substances to them. Others interfere with the ability
      of cancer cells to grow and spread. Gemtuzumab may also stop the growth of promyelocytic
      leukemia by blocking blood flow to the cancer. Giving gemtuzumab together with combination
      chemotherapy may be more effective in treating promyelocytic leukemia.

      PURPOSE: This phase II trial is studying how well giving gemtuzumab together with combination
      chemotherapy works in treating patients with previously untreated promyelocytic leukemia.
    

Detailed description: 
      OBJECTIVES:

        -  To assess the event-free survival and death during the first six weeks in patients with
           previously untreated, high-risk acute promyelocytic leukemia treated with a combined
           regimen of tretinoin, arsenic trioxide, and gemtuzumab ozogamicin.

        -  To estimate the frequency and severity of toxicities of this regimen in this group of
           patients.

        -  To investigate the molecular response rate utilizing this regimen in high-risk patients.

      OUTLINE:

        -  Induction chemotherapy: Patients receive oral tretinoin twice daily beginning on day 1
           until CR (up to 90 days), gemtuzumab ozogamicin IV over 2 hours on day 1, and arsenic
           trioxide IV over 2 hours 5 days a week beginning on day 10 until CR (up to 60 days) in
           the absence of disease progression or unacceptable toxicity. Patients achieving A1 bone
           marrow, B1 peripheral blood, and C1 extramedullary disease status proceed to
           consolidation therapy after maintaining B1 peripheral blood status for ≥ 7 days.

        -  Consolidation therapy: Beginning between 2-8 weeks after documentation of complete
           response (CR), patients receive consolidation therapy.

             -  Consolidation courses 1 and 2: Patients receive arsenic trioxide IV over 2 hours 5
                days a week for 5 weeks. Treatment repeats every 7 weeks for up to 2 courses.
                Patients remaining in A1 bone marrow, B1 peripheral blood, and C1 extramedullary
                disease status continue with consolidation courses 3 and 4.

             -  Consolidation courses 3 and 4: Within 4 weeks of completing consolidation course 2,
                patients receive oral tretinoin twice daily on days 1-7 and daunomycin IV bolus or
                over 1 hour on days 1-3. Within 2-8 weeks after recovery to B1 peripheral blood
                status, patients receive consolidation course 4 as in course 3. Patients who remain
                in B1 peripheral blood and C1 extramedullary disease status continue on
                consolidation courses 5 and 6.

             -  Consolidation courses 5 and 6: Beginning between 2-8 weeks after recovery to B1
                peripheral blood status, patients receive gemtuzumab IV over 2 hours on day 1.
                Between 2-8 weeks after recovery to B1 peripheral blood status, patients receive
                consolidation course 6 as in course 5. Patients who remain in A1 bone marrow, B1
                peripheral blood, and C1 extramedullary disease status proceed to maintenance
                therapy.

        -  Maintenance therapy: Beginning 2-8 weeks after recovery of blood counts, patients
           receive oral tretinoin twice daily on days 1-7 every other week for 1 year, oral
           mercaptopurine once daily for 1 year, and oral methotrexate once weekly for 1 year.

      Patients undergo bone marrow aspirates and biopsies periodically during study. Samples are
      analyzed for cytogenetics by fluorescence in situ hybridization (FISH) and for PML-RARα by
      polymerase chain reaction (PCR).

      After completion of study treatment, patients are evaluated at 3, 6, 9, 12, 18, 24, and 36
      months.
    

Intervention name(s): arsenic trioxide; gemtuzumab ozogamicin; mercaptopurine; methotrexate; tretinoin
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Methotrexate; Mercaptopurine; Arsenic Trioxide; Tretinoin; Gemtuzumab
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult acute promyelocytic leukemia (M3); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); untreated adult acute myeloid leukemia