PKC412, Daunorubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Condition: Acute Myeloid Leukemia (AML)
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: PKC412 may stop the growth of cancer cells by blocking the enzymes necessary for
      their growth. It may also increase the effectiveness of daunorubicin and cytarabine by making
      cancer cells more sensitive to the drugs. Drugs used in chemotherapy, such as daunorubicin
      and cytarabine, work in different ways to stop cancer cells from dividing so they stop
      growing or die. Combining PKC412 with chemotherapy may kill more cancer cells.

      PURPOSE: This phase I trial is studying the side effects and best way to give PKC412 when
      given either after or together with daunorubicin and cytarabine in treating patients with
      newly diagnosed acute myeloid leukemia.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the safety and tolerability of PKC412 administered sequentially or
           concurrently with induction chemotherapy comprising daunorubicin and cytarabine followed
           by consolidation therapy comprising high-dose cytarabine in patients with newly
           diagnosed acute myeloid leukemia.

        -  Compare the pharmacokinetics of these regimens in these patients.

      Secondary

        -  Determine the efficacy of these regimens, in terms of response rate, disease-free
           survival, and overall survival, in these patients.

        -  Correlate genetic variation in drug metabolism genes, leukemia genes, and drug target
           genes with response in patients treated with these regimens.

      OUTLINE: This is an open-label, multicenter study. Patients are alternately assigned to 1 of
      2 induction treatment groups.

        -  Induction therapy:

             -  Group I (sequential therapy): Patients receive daunorubicin IV over 30 minutes on
                days 1-3, cytarabine IV continuously on days 1-7, and oral PKC412 twice daily on
                days 8-21 in the absence of disease progression or unacceptable toxicity.

             -  Group II (concurrent therapy): Patients receive daunorubicin and cytarabine as in
                group I and oral PKC412 twice daily on days 1-7 and 15-21 in the absence of disease
                progression or unacceptable toxicity.

      In both groups, patients are evaluated on day 28. Patients with persistent disease receive a
      second induction course comprising daunorubicin IV over 30 minutes on days 1 and 2,
      cytarabine IV continuously on days 1-5, and oral PKC412 on the same schedule as their
      assigned treatment group. Patients with a complete response after course 1 or course 2
      proceed to consolidation therapy.

        -  Consolidation therapy: Patients in both groups receive high-dose cytarabine IV over 3
           hours twice daily on days 1, 3, and 5 and oral PKC412 on the same schedule as their
           assigned treatment group. Treatment repeats every 28-42 days for 3 courses in the
           absence of disease progression or unacceptable toxicity.

      After completion of consolidation therapy, patients in both groups continue to receive PKC412
      alone, according to their assigned treatment group, every 28-42 days for up to 3 years in the
      absence of disease progression or unacceptable toxicity.

      Patients are followed every 3 months.
    

Intervention name(s): cytarabine; daunorubicin hydrochloride; midostaurin
Intervention type(s): Drug; Drug; Drug
Other intervention name(s): PKC412
Intervention MeSH terms: Cytarabine; Daunorubicin; Midostaurin
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); untreated adult acute myeloid leukemia