A Phase II, Randomized, Comparative Trial of Standard of Care, With or Without Midostaruin to Prevent Relapse Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients With FLT3-ITD Mutated Acute Myeloid Leukemia
Trial status: Open for Enrollment
Why is this study being done?
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,
Who is eligible to participate?
- Patients must be between 18 and 60 years of age
- Patients must have an ECOG Performance Status of < 2
- Patients must have a documented Unequivocal diagnosis of AML according to WHO 2008 classification (>20% blasts in the bone marrow), excluding M3 (acute promyelocytic leukemia).
- Patients must have a documented FLT3 ITD mutation, determined by local laboratory for eligibility (historical tissue will be requested for central analysis confirmation)
- Patients who have undergone allogeneic HSCT in CR1 from a matched related or matched unrelated donor. All of the following criteria must also 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 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 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
- Patients whom have failed prior attempts at allogeneic HSCT
- Patients who have 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 are 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 requires 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 use highly effective methods of contraception during dosing and for 30 days after treatment completion
Other protocol-defined inclusion/exclusion criteria may apply