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Clinical Trial VICCHEM1346


A Phase II, Randomized, Comparative Trial of Standard of Care, with or without Midostaurin to Prevent Relapse Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients with FLT3-ITD Mutated Acute Myeloid Leukemia

Principal Investigator(s)

Sanjay Mohan


  • Protocol No. VICCHEM1346
  • Open Date: 01/21/2014
  • Staging: Phase II
  • Age Group: Adults
  • Scope: National
  • Objective: To determine if the addition of midostaurin to standard of care (SOC) therapy reduces relapse after at least 18 months of follow-up following allogeneic HSCT in FLT3-ITD mutant AML patients in first complete remission (CR1)
  • Disease Sites: Leukemia; Hematologic
  • Therapies: Molecular Targeted Agents / Immunotherapy / Biologics
  • Drugs: Midostaurin (PKC412)
  • Participating Institutions: Vanderbilt University
  • National Clinical Trial ID: NCT01883362
  • Secondary Protocol No: CPKC412AUS23


Patients with acute myeloid leukemia (AML) with the FLT3-ITD mutation are invited to take part in this study. The purpose of this study is to find out if the addition of a drug called midostaurin (PKC412) given to patients with AML that have a FLT3-ITD mutation and who have received an allogeneic stem cell transplant can reduce the risk of relapse or having the disease reappear. Patients in this study will have a 50% chance of being treated with either standard of care treatment with midostaurin or standard of care treatment alone. This study will assess which of these two treatments gives better relief of preventing AML from coming back after transplant. Because we do not know which treatment is best, we need to make comparisons. Midostaurin is a medicine that has not been approved by any health authorities for the treatment of people with AML. Midostaurin is currently not available for you to buy in any country. So far midostaurin has been given to about 1700 patients, including healthy volunteers, cancer patients, and patients with diabetes mellitus. About 60 patients will join in this study at 20 centers in the US and Canada: 30 patients will receive standard of care alone and 30 patients will be treated with Standard of Care plus midostaurin.


Ages Eligible for Study:18 Years to 60 Years
Genders Eligible for Study:Both
Accepts Healthy Volunteers:No


Inclusion Criteria:
• 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
Exclusion Criteria:
• 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