Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML
Condition: Acute Myeloid Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Midostaurin; Standard of Care
Intervention description: Midostaurin was supplied in 25mg soft gelatin capsule taken orally twice a day for 28 days of each cycle. Patients will be treated for 12 cycles.; Standard of Care was not defined per protocol. The investigator prescribed based on the commonly used medications given in the post SCT setting.
Intervention MeSH terms: Midostaurin
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: acute myeloid leukemia; AML; FLT3-ITD; midostaurin; PKC412; allogeneic hematopoeitic stem cell tranplant; SCT; HSCT; CR1; adult

Summary:

      To determine if the addition of midostaurin (PKC412) to Standard of Care (SOC) therapy
      reduces relapse in FLT3-ITD mutated AML patients receiving an allogenetic hematopoietic stem
      cell transplant,
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients between 18 and 70 years of age

          -  Patients with ECOG Performance Status of ≤ 2

          -  Patients with a documented unequivocal diagnosis of AML according to WHO 2008
             classification (>20% blasts in the bone marrow), excluding M3 (acute promyelocytic
             leukemia).

          -  Patients with a documented FLT3 ITD mutation, determined by local laboratory for
             eligibility (historical tissue will be requested for central analysis confirmation)

          -  Patients who undersent allogeneic HSCT in CR1 from a matched related or matched
             unrelated donor. All of the following criteria had to be met: HLA typing to include
             available 8/8 or 7/8 allele HLA matched donor (at A,B,C, DRB1) Single allelic mismatch
             allowed

          -  Patients who had received a conditioning regimen which included one of the following:

        Busulfan/Fludarabine (Bu/Flu) Busulfan (16 mg/kg PO or 12.8 mg/kg IV) Fludarabine (120-180
        mg/m2) Fludarabine / Melphalan (Flu/Mel) Fludarabine (120-180 mg/m2) Melphalan (≤ 150
        mg/m2) Busulfan/Cyclophosphamide (Bu/Cy) Busulfan (16 mg/kg PO or 12.8 mg/kg IV)
        Cyclophosphamide (120 mg/kg) Cyclophosphamide/Total Body Irradiation (Cy/TBI)
        Cyclophosphamide (120 mg/kg) TBI (1200-1420 cGy)

        • Recovery of counts by day 42 and was able to start midostaurin by day 60 post-HSCT (first
        dose of midostaurin to start no earlier than 28 days post-HSCT); ANC >1000µL, platelets
        ≥20,000 without platelet transfusion

        Exclusion Criteria:

        Patients eligible for this study must not have met any of the following criteria:

          -  Patients who failed prior attempts at allogeneic HSCT

          -  Patients who had received an autologous transplant

          -  Patients with Acute GVHD Grade III-IV

          -  Patients with a known confirmed diagnosis of HIV infection or active viral hepatitis.

          -  Impaired cardiac function including any of the following:

               -  Screening ECG with a QTc > 450 msec. If QTc > 450 and electrolytes were not
                  within normal ranges, electrolytes should be corrected and then the patient
                  rescreened for QTc.

               -  Patients with congenital long QT syndrome

               -  History or presence of sustained ventricular tachycardia

               -  Any history of ventricular fibrillation or torsades de pointes

               -  Bradycardia defined as HR. < 50 bpm

               -  Right bundle branch block + left anterior hemiblock (bifascicular block)

               -  Patients with myocardial infarction or unstable angina < 6 months prior to
                  starting study

               -  Congestive Heart Failure NY Heart Association class III or IV

               -  Patients with an ejection fraction < 45% assessed by MUGA or ---ECHO within 28
                  days prior to starting study cycle 1 (of midostaurin or control group)

          -  Patients with any pulmonary infiltrate including those suspected to be of infectious
             origin (unless resolves to ≤ Grade 1 within screening timeframe)

          -  Patient required treatment with strong CYP3A4 inhibitors or moderate or strong CYP3A4
             inducers other than those required for GVH or infection prophylaxis or treatment

        Pregnant or nursing (lactating) women, or women of child-bearing potential, must have used
        highly effective methods of contraception during dosing and for 30 days after treatment
        completion