Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia

Phase 2

Active, not recruiting

Interventions: Drug: Gilteritinib
Drug: Midostaurin
Drug: Daunorubicin
Drug: Cytarabine

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

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

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

Locations (44): HonorHealth Research Institute
🇺🇸
Scottsdale, Arizona, United States
University of California, San Francisco-Fresno (University Oncology Associates)
🇺🇸
Clovis, California, United States
UCLA
🇺🇸
Los Angeles, California, United States
Kaiser Permanente Oakland
🇺🇸
Oakland, California, United States
UC Irvine Health
🇺🇸
Orange, California, United States
Kaiser Permanente Roseville
🇺🇸
Roseville, California, United States
Kaiser Permanente Santa Clara
🇺🇸
Santa Clara, California, United States
Mayo Clinic- Jacksonville, FL
🇺🇸
Jacksonville, Florida, United States
Augusta University Medical Center
🇺🇸
Augusta, Georgia, United States
University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
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HonorHealth Research Institute
🇺🇸Scottsdale, Arizona, United States