Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Registration Number
- NCT03836209
- Lead Sponsor
- PrECOG, LLC.
- Brief Summary
Eligible untreated patients with FLT3 acute myeloid leukemia (AML) between the ages of 18 and 70 will be randomized to receive gilteritinib or midostaurin during induction and consolidation. Patients will also receive standard chemotherapy of daunorubicin and cytarabine during induction and high-dose cytarabine during consolidation.
Gilteritinib, is an oral drug that works by stopping the leukemia cells from making the FLT3 protein. This may help stop the leukemia cells from growing faster and thus may help make chemotherapy more effective. Gilteritinib has been approved by the Food and Drug Administration (FDA) for patients who have relapsed or refractory AML with a FLT3 mutation but is not approved by the FDA for newly diagnosed FLT3 AML, and its use in this setting is considered investigational.
Midostaurin is an oral drug that works by blocking several proteins on cancer cells, including FLT3 that can help leukemia cells grow. Blocking this pathway can cause death to the leukemic cells. Midostaurin is approved by the FDA for the treatment of FLT3 AML.
The purpose of this study is to compare the effectiveness of gilteritinib to midostaurin in patients receiving combination chemotherapy for FLT3 AML.
- Detailed Description
Approximately one third of patients with AML have a particular change in their leukemia cells (called a mutation) in a gene called FLT3. The presence of a FLT3 mutation can be used to direct treatment options.
This is an open-label phase II study. Patients will receive standard chemotherapy of daunorubicin and cytarabine during Induction and high-dose cytarabine during Consolidation. Patients will be randomized to gilteritinib or midostaurin. After approximately 90 patient's complete treatment, a review of the effectiveness of gliteritinib compared to midostaurin will be done. If gilteritinib is not as effective as midostaurin, the study may be stopped.
Bone marrow aspirate and biopsy will be done on Day 21 after start of Induction and after Induction to assess response. Patients with a complete response may proceed to consolidation chemotherapy. Another bone marrow aspirate and biopsy will be done after the first cycle of consolidation is complete.
Mandatory prescreening bone marrow and/or blood samples are required for FLT3 testing. Any left-over samples will be requested for future research (optional).
Mandatory bone marrow samples for research are required after Induction and if patient receives Consolidation, after the first cycle of Consolidation.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 181
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Daunorubicin Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Arm B Daunorubicin Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Arm A Cytarabine Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Arm A Gilteritinib Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib. Arm B Midostaurin Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin. Arm B Cytarabine Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin.
- Primary Outcome Measures
Name Time Method FLT3 Mutation Negative Composite Complete Response (CRc) [Includes Complete Response (CR) or CR With Incomplete Hematologic Recovery (CRi)] at End of Induction 3 months FLT3 mutation negative (evaluated by polymerase chain reaction \[PCR\]) Composite Complete Response (CRc) \[includes CR and CRi\] rate after induction treatment and complete MRD assessment. The cut points used for FLT3 mutation negative are 1% (equivalent to 10-2) for FLT3-TKD and 10-4 for FLT3-ITD.
- Secondary Outcome Measures
Name Time Method FLT3 Mutation Negative Complete Response (CR) Rate at End of Induction 3 months CR evaluated by FLT3 testing after Induction
Minimal Residual Disease (MRD)- CRc Rate at End of Induction 3 months MRD- CRc evaluated by flow cytometry after Induction
CRc (CR or CRi) Rate at End of Induction 3 months CRc assessed in accordance with 2017 European LeukemiaNet (ELN)
Event Free Survival (EFS) 68 months EFS assessed in accordance with 2017 ELN
Overall Survival (OS) 68 months OS assessed in accordance with 2017 ELN
Number of Participants Treatment-related Adverse Events as Assessed by CTCAE v5.0 10 months Number of participants with abnormal laboratory values and/or adverse events
Trial Locations
- Locations (44)
UCLA
🇺🇸Los Angeles, California, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
HonorHealth Research Institute
🇺🇸Scottsdale, Arizona, United States
Franciscan Health Indianapolis
🇺🇸Indianapolis, Indiana, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
Mayo Clinic- Rochester, MN
🇺🇸Rochester, Minnesota, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
University of California, San Francisco-Fresno (University Oncology Associates)
🇺🇸Clovis, California, United States
UC Irvine Health
🇺🇸Orange, California, United States
Kaiser Permanente Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente Roseville
🇺🇸Roseville, California, United States
Mayo Clinic- Jacksonville, FL
🇺🇸Jacksonville, Florida, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Kaiser Permanente Santa Clara
🇺🇸Santa Clara, California, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Augusta University Medical Center
🇺🇸Augusta, Georgia, United States
University of Kentucky Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Northwell Health
🇺🇸Lake Success, New York, United States
Atlantic Health Systems/Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Mount Sinai
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Weill Cornell Medicine New York Presbyterian Hospital
🇺🇸New York, New York, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Geisinger Medical Center
🇺🇸Danville, Pennsylvania, United States
University of Oklahoma Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
MultiCare
🇺🇸Spokane, Washington, United States
Marshfield Medical Center
🇺🇸Marshfield, Wisconsin, United States
University of Wisconsin Clinical Science Center
🇺🇸Madison, Wisconsin, United States
UW Cancer Center at ProHealth Care
🇺🇸Waukesha, Wisconsin, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
St. Joseph's Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States