Phase III Trial in Acute Promyelocytic Leukemia Patients
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Promyelocytic, Acute
Study type: Interventional
Phase: Phase 3

Summary: 
      Open label, randomised, phase III multicenter trial.
    

Detailed description: 
      -  Arm I:

             -  Induction therapy: Patients receive oral tretinoin twice daily and arsenic trioxide
                IV over 2 hours on days 1-60. Patients achieving hematological complete remission
                go on to receive consolidation therapy.

             -  Consolidation therapy: Patients receive oral tretinoin twice daily on days 1-14.
                Treatment with tretinoin repeats every 4 weeks for up to 7 courses. Patients also
                receive arsenic trioxide IV over 2 hours on days 1-5 in weeks 1-4. Treatment with
                arsenic trioxide repeats every 8 weeks for up to 4 courses.

        -  Arm II:

             -  Induction therapy: Patients receive tretinoin as in arm I induction therapy and
                idarubicin IV over 20 minutes on days 2, 4, 6, and 8. Patients achieving
                hematological complete remission go on to receive consolidation therapy.

             -  Consolidation therapy: Patients receive oral tretinoin twice daily on days 1-45,
                idarubicin IV over 20 minutes on days 1-4 and day 31, and mitoxantrone
                hydrochloride IV over 30 minutes on days 16-20.

      Marrow samples are collected after completion of consolidation therapy and analyzed by
      reverse transcriptase-PCR for molecular remission. Patients achieving molecular remission
      (PML-RARa negative) go on to receive maintenance therapy.

        -  Maintenance therapy: Patients receive oral mercaptopurine once daily and methotrexate
           intramuscularly once weekly for 3 months. Treatment with mercaptopurine and methotrexate
           repeats every 3 months for 7 courses. After completion of course 1 of mercaptopurine and
           methotrexate, patients receive oral tretinoin once daily on days 1-15*. Treatment with
           tretinoin repeats every 3 months for 6 courses.

      NOTE: *Patients do not receive mercaptopurine and methotrexate during tretinoin
      administration.

      After completion of study therapy, patients are followed periodically for 5 years.

      As of 14th September 2010, all patients needed to evaluate the primary endpoint (162
      patients) have been recruited but the trial accrual continued in order to assess one
      secondary outcome (QoL)."
    

Intervention name(s): arsenic trioxide; idarubicin; mercaptopurine; methotrexate; all-trans retinoic acid; all-trans retinoic acid (ATRA)
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Induction Arsenic Trioxide (As2O3=ATO), 0.15 mg/Kg IV over 2 hours daily starting on day 1. ATO will be continued until hematological CR or for a maximum of 60 days.
Consolidation ATO, 0.15 mg/Kg IV over 2 hours daily for 5 days every week. Treatment will be continued for 4 weeks on and 4 weeks off, for a total of 4 cycles (last cycle administered on weeks 25 - 28).; Induction
Idarubicin, 12 mg/m² on days 2, 4, 6 and 8 by short (20') intravenous infusion .
If no hematological CR is achieved by 60 days after start of induction, patient will go off-study.
Consolidation
1st cycle Idarubicin, 5 mg/m2/day by short (20') intravenous infusion on days 1, 2, 3, 4.
3rd cycle Idarubicin, 12 mg/m2/day as short (20') intravenous infusion only on day 1.; Maintenance therapy 6-Mercaptopurine (6-MP), 50 mg/m2/day orally. The dose will be adjusted according to hematopoietic toxicity during the follow-up period; Maintenance therapy Methotrexate (MTX), 15 mg/m2/weekly intramuscularly. The dose will be adjusted according to toxicity during the follow-up period.; Induction ATRA, 45 mg/m²/day will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment, starting on day 1. ATRA treatment will be continued until hematological CR and for a maximum of 60 days.
Consolidation
st cycle ATRA, 45 mg/m2/day, will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment, starting from day 1 to day 15.
nd cycle ATRA, 45 mg/m2/day will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment, starting from day 1 to day 15.
rd cycle ATRA, 45 mg/m2/day will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment, starting from day 1 to day 15.
Maintenance therapy
ATRA, 45 mg/m2/day orally, for 15 days every three months until a two year period is completed.; Induction All-trans retinoic acid (ATRA), 45 mg/m²/day will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment, starting on day 1. ATRA treatment will be continued until hematological complete remission (CR, see below for definition) or for a maximum of 60 days.
Consolidation ATRA, 45 mg/m²/day will be administered orally in two equally divided doses and rounded to the nearest 10 mg increment. Treatment will be administered for 2 weeks on 2 weeks off and for a total of 7 cycles (last cycle administered on weeks 25 - 26).
Intervention MeSH terms: Methotrexate; Mercaptopurine; Idarubicin; Tretinoin; Arsenic Trioxide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult acute promyelocytic leukemia (M3); adult acute myeloid leukemia with t(15;17)(q22;q12); untreated adult acute myeloid leukemia