Blood Cancer


Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia

STATUS: Closed to Accrual

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.
  • Registration Criteria: - Any patient undergoing bone marrow biopsy with suspicion of or known diagnosis of acute myeloid leukemia (AML) will be asked to sign a Prescreening Consent to allow for centralized testing of bone marrow/peripheral blood samples. Randomization Eligibility Criteria: - Patient must have previously untreated FLT3 mutated Non M3 AML (FLT3-TKD or FLT3-ITD allowed). ° Standard of care induction 7+3 chemotherapy may start prior to randomization using same regimen and doses as defined in the protocol while awaiting prescreening test results. - Patient must have had no prior systemic therapy for AML, except as noted below: - Hydroxyurea and emergent leukapheresis or preemptive treatment with retinoic acid prior to exclusion of Acute Promyelocytic Leukemia (APL) allowed. - Prior therapy for myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN) (e.g., thalidomide or lenalidomide, interferon, jakafi, cytokines, 5-azacytidine or decitabine, histone deacetylase inhibitors). - Initiation of standard of care 7+3 induction chemotherapy using same regimen and doses as defined in protocol while awaiting prescreening test results - Patient may not have received hypomethylating agent within 21 days. - Patient may not have M3 AML. - Patient may not have AML with known Core Binding Factor -t(8;21), inv(16), t(16;16). - Patient may not have known active Central Nervous System (CNS) leukemia. ° Prophylaxis with intrathecal chemotherapy is allowed prior to or during induction/consolidation. - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3. - Patient must be age ≥ 18 years to ≤ 70 years. - Patient must be able to understand and willing to sign Institutional Review Board (IRB)-approved informed consent. - Patient must be willing to provide mandatory bone marrow and blood samples for research. - Patient must have adequate organ function as measured by the following criteria, obtained ≤ 48 hours prior to randomization except ECG and left ventricular ejection fraction (LVEF) which can be done ≤ 2 weeks prior to randomization: - Serum creatinine ≤ 1.5x institutional upper limit of normal (ULN), or if serum creatinine outside normal range, then glomerular filtration rate (GFR) >40 mL/min as measured by Cockcroft-Gault formula. - Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 3x ULN, unless secondary to leukemia. - Serum total or direct bilirubin <2 mg/dL, unless due to Gilbert's, hemolysis or leukemic infiltration. - Fridericia-Corrected QT Interval (QTcF) interval ≤ 500 msec (using Friderica's correction). - Left Ventricular Ejection Fraction >45%. - The patient may not be known to have hypokalemia and/or hypomagnesemia that does not respond to supplementation. - A female patient is eligible to participate if she is not pregnant and at least one of the following conditions apply: - Not a woman of childbearing potential (WOCBP) OR - WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 180 days after the final study drug administration. - Female patient must agree not to breastfeed or donate ova starting at treatment and throughout the study period, and for at least 180 days after the final study drug administration. - A male patient must agree not to donate sperm starting at treatment and throughout the study period, and for at least 120 days after the final study drug administration. - A male patient with female partner(s) of child-bearing potential must agree to use contraception during the treatment period, and for at least 120 days after the final study drug administration. - Male patient with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the treatment period, and for at least 120 days after the final study drug administration. - Patient may not have another malignancy that could interfere with the evaluation of safety or efficacy of this combination. - Patient may not have a history of Long QT Syndrome. - Patient may not have evidence of uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, or congestive heart failure (CHF) New York Heart Association (NYHA) Class 3 or 4. Patient may also not have a history of CHF NYHA Class 3 or 4 in the past, unless a prescreening echocardiogram (ECHO) or multigated acquisition scan (MUGA) performed within 2 weeks prior to study entry with results of left ventricular ejection fraction >45%. - Patient may not have had major surgery or radiation therapy within 4 weeks of registration. - Patient may not require treatment with concomitant drugs that are strong inducers of CYP3A and P-gp. - Patient with a known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent are not eligible. - Patient with known gastrointestinal (GI) disease or prior GI procedure that could interfere with the oral absorption or tolerance of gilteritinib or midostaurin including difficulty swallowing are not eligible. - Patient with any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of the treatment according to the protocol are not eligible. - Patient may not participate in any other therapeutic clinical trials, including those with other investigational agents not included in this trial during treatment on this study without prior approval from PrECOG.

United States
Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Contact: Vladimir Kustanovich

UC Irvine Health/Chao Family Comprehensive Cancer Center

Mayo Clinic in Florida

Northwestern University

University of Chicago Comprehensive Cancer Center

University of Kentucky/Markey Cancer Center

Massachusetts General Hospital Cancer Center

Johns Hopkins University/Sidney Kimmel Cancer Center

Mayo Clinic in Rochester

University of Nebraska Medical Center

New York
Icahn School of Medicine at Mount Sinai

Memorial Sloan Kettering Cancer Center
Contact: Ellin Berman

Case Comprehensive Cancer Center

Oklahoma City
University of Oklahoma Health Sciences Center

Thomas Jefferson University Hospital

University of Pennsylvania/Abramson Cancer Center

University of Pittsburgh Cancer Institute (UPCI)

Vanderbilt University/Ingram Cancer Center

University of Wisconsin Carbone Cancer Center - University Hospital

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.

Interactive content above is from the official study record on the National Cancer Institute website,

This trial is by the PrECOG research group, which supports the mission of the ECOG-ACRIN Cancer Research Group.

PrECOG 60px
ECOG-ACRIN Cancer Research Group