Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML
Conditions
Acute Myeloid Leukemia
Conditions: official terms
Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
acute myeloid leukemia, AML, FLT3-ITD, midostaurin, PKC412, allogeneic hematopoeitic stem cell tranplant, SCT, HSCT, CR1
Study Type
Interventional
Study Phase
Phase 2
Study Design
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
Intervention
Name: Midostaurin (PKC412) Type: Drug
Name: Standard of Care Type: Other
Overall Status
Recruiting
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,
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 60 Years
Minimum Age: 18 Years
Gender: Both
Criteria: 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
Locations
City of Hope National Medical Center Oncology
Duarte, California, United States
Status: Withdrawn
University of California San Diego Moores Cancer Center
La Jolla, California, United States
Status: Not yet recruiting
University of California at Los Angeles Oncology
Los Angeles, California, United States
Status: Recruiting
Contact: - 310-825-5513
Sarah Cannon Research Institute
Denver, Colorado, United States
Status: Recruiting
Contact: - 720-754-4800
H. Lee Moffitt Cancer Center & Research Institute Oncology
Tampa, Florida, United States
Status: Recruiting
Contact: - 813-745-6012
Northside Hospital
Atlanta, Georgia, United States
Status: Not yet recruiting
Contact: - 404-851-5926
University of Chicago Medical Center
Chicago, Illinois, United States
Status: Recruiting
Contact: - 773-834-2487
University of Louisville / James Graham Brown Cancer Center Brown Cancer Center (2)
Louisville, Kentucky, United States
Status: Not yet recruiting
Contact: - 502-562-4351
John Hopkins University - Kimmel Comp. Cancer Center Oncology
Baltimore, Maryland, United States
Status: Withdrawn
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Status: Recruiting
Contact: - 617-724-1124
Karmanos Cancer Institute Karmanos - Wayne State
Detroit, Michigan, United States
Status: Recruiting
Contact: - 313-576-8093
Mayo Clinic - Rochester
Rochester, Minnesota, United States
Status: Recruiting
Contact: - 507-284-2467
Washington University School Of Medicine-Siteman Cancer Ctr Washington U School of Med
St. Louis, Missouri, United States
Status: Recruiting
Contact: - 314-454-8323
Hackensack University Medical Center Hackensack Univ Med Ctr (32)
Hackensack, New Jersey, United States
Status: Recruiting
Contact: - 201-336-8297
Memorial Sloan Kettering Cancer Center Oncology
New York, New York, United States
Status: Recruiting
Contact: - 212-639-3859
University of North Carolina at Chapel Hill University of North Carolina 6
Chapel Hill, North Carolina, United States
Status: Recruiting
Contact: - 919-966-7746
Duke Clinical Research Institute Oncology
Durham, North Carolina, United States
Status: Withdrawn
University Hospitals Case Medical Center
Cleveland, Ohio, United States
Status: Recruiting
Contact: - 216-844-8447
Ohio State Comprehensive Cancer Center/James Cancer Hospital Ohio State University
Columbus, Ohio, United States
Status: Withdrawn
Oregon Health Sciences University
Portland, Oregon, United States
Status: Recruiting
Contact: - 503-494-8945
Tennessee Oncology Sarah Cannon Research Inst.
Nashville, Tennessee, United States
Status: Recruiting
Contact: - 615-339-7274
Vanderbilt Univeristy Oncology
Nashville, Tennessee, United States
Status: Recruiting
Contact: - 615-936-8422
Baylor Health Care System/Sammons Cancer Center Oncology
Dallas, Texas, United States
Status: Recruiting
Contact: - 214-818-8471
University of Texas/MD Anderson Cancer Center
Houston, Texas, United States
Status: Withdrawn
Texas Transplant Physicians Group Oncology 2
San Antonio, Texas, United States
Status: Recruiting
Contact: - 210-575-6904
Virginia Commonwealth University Virginia Commonwealth Univ.
Richmond, Virginia, United States
Status: Not yet recruiting
Fred Hutchinson Cancer Research Center Oncology
Seattle, Washington, United States
Status: Recruiting
Contact: - 206-667-1990
University of Wisconsin Oncology
Madison, Wisconsin, United States
Status: Withdrawn
Novartis Investigative Site
Toronto, Ontario, Canada
Status: Recruiting
Start Date
February 2014
Completion Date
March 2018
Sponsors
Novartis Pharmaceuticals
Source
Novartis
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page