Status:
COMPLETED
Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML
Lead Sponsor:
Novartis Pharmaceuticals
Conditions:
Acute Myeloid Leukemia
Eligibility:
All Genders
18-70 years
Phase:
PHASE2
Brief 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
- 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
- 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
Key Trial Info
Start Date :
February 6 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
April 30 2018
Estimated Enrollment :
60 Patients enrolled
Trial Details
Trial ID
NCT01883362
Start Date
February 6 2014
End Date
April 30 2018
Last Update
March 17 2021
Active Locations (19)
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1
University of California San Diego Moores Cancer Center
La Jolla, California, United States, 92093-0987
2
University of California at Los Angeles Oncology
Los Angeles, California, United States, 90095
3
SCRI- Colorado Blood Cancer Institute
Denver, Colorado, United States, 80218
4
H Lee Moffitt Cancer Center and Research Institute Oncology
Tampa, Florida, United States, 33612