Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: cytarabine; daunorubicin; midostaurin; placebo; dexamethasone acetate
Intervention description: Given IV; Given IV; Given orally; Given orally; ocular medication administration
Intervention MeSH terms: Cytarabine; Dexamethasone; Dexamethasone acetate; Daunorubicin; Midostaurin; BB 1101
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 717.0
Sex: All
Minimum age: 18 Years
Maximum age: 59 Years
Healthy volunteers: No
Keywords: adult acute basophilic leukemia; adult acute eosinophilic leukemia; adult acute lymphoblastic leukemia; adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); adult acute myelomonocytic leukemia (M4); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); untreated adult acute myeloid leukemia

Summary:

      The purpose of this study is to compare the effects, good and/or bad, of a standard
      chemotherapy regimen for AML that includes the drugs daunorubicin and cytarabine combined
      with or without midostaurin (also known as PKC412), to find out which is better. This
      research is being done because it is unknown whether the addition of midostaurin to
      chemotherapy treatment is better than chemotherapy treatment alone. Midostaurin has been
      tested in over 400 patients and is being studied in a number of illnesses, including AML,
      colon cancer, and lung cancer. Midostaurin blocks an enzyme, produced by a gene known as
      FLT3, that may have a role in the survival and growth of AML cells. Not all leukemia cells
      will have the abnormal FLT3 gene. This study will focus only on patients with leukemia cells
      with the abnormal FLT3 gene.
    

Eligibility criteria:

        1. Documentation of Disease:

               -  Unequivocal diagnosis of AML ( > 20% blasts in the bone marrow based on the WHO
                  classification), excluding M3 (acute promyelocytic leukemia). Patients with
                  neurologic symptoms suggestive of CNS leukemia are recommended to have a lumbar
                  puncture. Patients whose CSF is positive for AML blasts are not eligible.

               -  Documented FLT3 mutation (ITD or point mutation), determined by analysis in a
                  protocol- designated FLT3 screening laboratory.

          2. Age Requirement:

               -  Age ≥ 18 and < 60 years

          3. Prior Therapy:

               -  No prior chemotherapy for leukemia or myelodysplasia with the following
                  exceptions:

                    -  emergency leukapheresis

                    -  emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 5 days

                    -  cranial RT for CNS leukostasis (one dose only)

                    -  growth factor/cytokine support

               -  AML patients with a history of antecedent myelodysplasia (MDS) remain eligible
                  for treatment on this trial, but must not have had prior cytotoxic therapy (e.g.,
                  azacitidine or decitabine)

               -  Patients who have developed therapy related AML after prior RT or chemotherapy
                  for another cancer or disorder are not eligible.

          4. Cardiac Function: Patients with symptomatic congestive heart failure are not eligible.

          5. Initial Laboratory Value: Total bilirubin < 2.5 x ULN (Upper Limit of Normal)

          6. Pregnancy and Nursing Status:

               -  Non-pregnant and non-nursing due to the unknown teratogenic potential of
                  midostaurin in humans, pregnant or nursing patients may not be enrolled.

               -  Women of childbearing potential must have a negative serum or urine pregnancy
                  test within a sensitivity of at least 50 mIU/mL within 16 days prior to
                  registration.

               -  Women of child-bearing potential must either commit to continued abstinence from
                  heterosexual intercourse or commit to TWO acceptable methods of birth control:

                    -  one highly effective method (eg, IUD, hormonal (non-oral contraceptive),
                       tubal ligation, or partner's vasectomy) and

                    -  one additional effective method (e.g., latex condom, diaphragm or cervical
                       cap)

               -  The two acceptable methods of birth control must be used AT THE SAME TIME, before
                  beginning midostaurin/placebo therapy and continuing for 12 weeks after
                  completion of all therapy.

               -  Note that oral contraceptives are not considered a high effective method because
                  of the possibility of a drug interaction with midostaurin.

               -  Women of childbearing potential is defined as a sexually active mature woman who
                  has not undergone a hysterectomy or who has not had menses at any time in the
                  preceding 24 consecutive months.

               -  Men must agree not to father a child and must use a latex condom during any
                  sexual contact with women of childbearing potential while taking
                  midostaurin/placebo and for 12 weeks after therapy is stopped, even if they have
                  undergone a successful vasectomy.