Combination Chemotherapy Plus PSC 833 Followed by Interleukin-2 in Treating Patients With Acute Myelogenous 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. Some cancers may become resistant to chemotherapy drugs.
      Combining PSC 833 with chemotherapy may reduce resistance to the drugs and allow the cancer
      cells to be killed. Interleukin-2 may stimulate a person's white blood cells to kill leukemia
      cells.

      PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy plus PSC 833
      followed by additional chemotherapy or peripheral stem cell transplantation and interleukin-2
      in treating patients with untreated acute myelogenous leukemia.
    

Detailed description: 
      OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of daunorubicin when used in
      combination with etoposide, cytarabine, and PSC 833 (ADEP), and in combination with etoposide
      and cytarabine (ADE) in previously untreated patients with acute myelogenous leukemia who are
      less than 60 years. II. Determine the MTD of etoposide when used in combination with a
      constant dose of daunorubicin and cytarabine (ADE) in these patients. III. Determine the
      feasibility and toxic effects of administering postremission therapy in a risk adapted
      fashion, such that patients with favorable cytogenetic findings receive three
      intensifications with high dose cytarabine (HiDAC), while average to poor risk patients
      receive HiDAC/etoposide/filgrastim (G-CSF) for consolidation therapy and stem cell
      mobilization followed by peripheral stem cell (PBSC) transplant using busulfan/etoposide as
      the preparative regimen. IV. Determine the feasibility and toxic effects of the consolidation
      sequence of HiDAC/etoposide/G-CSF followed by 2 courses of HiDAC in patients who would
      otherwise receive PBSC transplant, but are unable to do so for logistical or institutional
      reasons. V. Determine the feasibility of intermittent administration of high dose
      subcutaneous interleukin-2 (IL-2) in combination with continuous low dose subcutaneous IL-2
      in patients recovering from PBSC transplant or intensive consolidation chemotherapy.

      OUTLINE: This is a dose escalation study of daunorubicin in the induction therapy portion,
      with a separate dose escalation study of etoposide in the same portion. Patients are treated
      with three phases of treatment: induction, intensification, and postremission therapy.
      Induction therapy: Patients receive cytarabine IV as a continuous infusion on days 1-7 plus
      daunorubicin IV over 30 minutes and etoposide IV over 2 hours on days 1-3 (ADE regimen). Some
      patients also receive PSC 833 IV as a continuous infusion on days 1-3 (ADEP regimen). This
      course may be repeated 14 days later. Cohorts of 9 patients each receive escalating doses of
      daunorubicin until the maximum tolerated dose (MTD) is reached. The MTD is defined as the
      dose at which 3 of 9 patients experience dose limiting toxicity. Escalations are conducted
      separately for the ADE and ADEP regimens. Other cohorts of 9 patients each receive escalating
      doses of etoposide with constant doses of daunorubicin in the ADE regimen. The MTD is
      described in the same manner. Intensification therapy: Arm I (patients with certain genetic
      characteristics in their leukemia cells): Patients receive 3 additional courses of cytarabine
      IV over 3 hours, twice a day, for 3 days. Courses are repeated every 28 days. Arm II
      (patients who do not have these genetic characteristics): Patients undergo a peripheral blood
      stem cell (PBSC) transplant. Patients first receive high dose cytarabine IV over 2 hours on
      days 1-4, etoposide IV as a continuous infusion on days 1-4, and filgrastim (G-CSF)
      subcutaneously beginning on day 5 until blood counts recover. PBSC are then collected.
      Approximately 4-6 weeks later, patients receive oral busulfan 4 times a day on days 1-4 and
      etoposide IV over 4 hours on day 5. PBSC are reinfused on day 7. G-CSF is administered
      subcutaneously beginning on day 7 until blood cell counts recover. Arm III (patients who
      cannot undergo a PBSC transplant): Patients receive cytarabine, etoposide, and G-CSF as in
      arm II, then high dose cytarabine as in arm I. Postremission therapy (all patients): Patients
      receive low dose interleukin-2 (IL-2) by daily injection for 2 weeks. On day 15, patients
      begin receiving intermittent high dose IL-2 three days a week. Patients alternate these
      courses of IL-2: 14 days of low dose IL-2, 3 days of high dose IL-2, 1 day of rest, low dose
      IL-2 for 10 days, then 3 days of high dose IL-2, then 1 day of rest. This course is repeated
      3 times. Patients then receive another 16 day course of low dose IL-2. Patients are followed
      at 1 month, then every 3 months for 2 years, then every 6 months for 2 years, then annually
      thereafter.

      PROJECTED ACCRUAL: Approximately 410 patients will be accrued into this study within 36
      months.
    

Intervention name(s): ara-C; Daunorubicin; Etoposide; PSC-833; Aldesleukin
Intervention type(s): Drug; Drug; Drug; Drug; Biological
Intervention MeSH terms: Aldesleukin; Etoposide; Daunorubicin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: untreated adult acute myeloid leukemia; adult acute erythroid leukemia (M6); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloblastic leukemia with maturation (M2); adult acute myelomonocytic leukemia (M4); adult acute monoblastic leukemia (M5a); adult acute megakaryoblastic leukemia (M7); adult acute monocytic leukemia (M5b); adult acute minimally differentiated myeloid leukemia (M0)