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PrE0905


Title PrE0905 Randomized Trial of Gilteritinib vs Midostaurin in FLT3 Mutated Acute Myeloid Leukemia (AML)
Therapeutic Area Acute Myeloid Leukemia
Principal Investigator Andreas Klein, MD
Min Age 18 Years
Max Age 65 Years
Gender Both
Contact NCCCR Staff
617-636-3264
NCCCR@tuftsmedicalcenter.org
More Information https://clinicaltrials.gov/ct2/show/NCT03836209?term=NCT03836209&draw=2&rank=1

Overview

The purpose of this study is to compare the effectiveness of gilteritinib to midostaurin in patients receiving standard combination chemotherapy for FLT3 AML. Patients receive standard chemotherapy with daunorubicin and cytarabine during induction and high-dose cytarabine during consolidation. These drugs are approved by the Food and Drug Administration (FDA) for the treatment of AML.

Gilteritinib, is an oral drug that works by blocking 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 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 is considered investigational in this study.

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.

 

Study Details

Inclusion Criteria

  • Patient must have previously untreated FLT3 mutated Non M3 AML (FLT3-TKD or FLT3-ITD allowed)
  • 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).

  •  Patients may not have hypomethylating agent within 21 days.

Exclusion Criteria

Hypokalemia and/or hypomagnesemia that does not respond to supplementation.

Study Requirements

Patients may receive treatment for approximately 9 months, and will be followed for up to 4 years after treatment ends or until the study closes.

Prior to Day 1 Induction

  • Physical exam
  • Vital signs (temperature, pulse, and B/P) including weight
  • Evaluation of activity level
  • Blood tests including complete blood count, chemistries, liver function and blood clotting tests
  • Research blood samples if receiving gilteritinib: 10 mL (approximately 2 teaspoons) of blood will be drawn and saved for future research (optional)
  • Review of all medications patient is taking including over-the-counter medicines, vitamins, dietary and herbal supplements
  • Monitoring of side effects

    Daily During Induction

    *Daily if admitted to hospital, otherwise weekly until blood counts reach a safe level

  • Physical exam
  • Vital signs (temperature, pulse, and B/P)*
  • Complete blood count test until blood counts reach a safe level, then twice weekly
  • Review of all medications patient is taking including over-the-counter medicines, vitamins, dietary and herbal supplements*
  • Monitoring of side effects

    Weekly During Induction

  • Evaluation of activity level
  • Blood tests including chemistries and liver function tests twice weekly
  • ECG will be done in triplicate (3 ECGs will be done at least 5 minutes apart) on Day 8 and Day 15 before patient receives gilteritinib or midostaurin

    Day 21 from Start of Cycle 1 Induction Only

    Day 22 from Start of Cycle 1 Induction Only (Optional)

    If a Second Cycle of Induction is needed

    End of Induction

    CONSOLIDATION: Up to 4 Cycles

    Prior to Each Consolidation Cycle

  • Physical exam
  • Vital signs (temperature, respirations, pulse, and B/P) including weight and evaluation of activity level
  • Blood tests including complete blood count, chemistries and liver function tests
  • Blood test to determine how quickly blood clots (PT, PTT and Fibrinogen) before Cycle 1, Day 1 then as clinically indicated
  • ECG in triplicate (3 ECGs will be done at least 5 minutes apart), then as clinically indicated
  • Review of all medications patient is taking including over-the-counter medicines, vitamins, dietary and herbal supplements
  • Monitoring of side effects

    Weekly During Consolidation

  • Physical exam
  • Complete blood count test twice weekly
  • Blood tests including chemistries and liver function tests

    Cycle 1, Day 14 from Start of Consolidation (Optional)

    End of Last Cycle of Consolidation

  • Bone marrow aspiration and biopsy to assess response to treatment. Some of the bone marrow sample will be sent for research for Minimal Residual Disease (MRD) analysis (measures the disease remaining after treatment). The remaining bone marrow sample will be stored for future research.

    End of Treatment

  • Physical exam
  • Vital signs (temperature, respirations, pulse, and B/P) including weight and evaluation of activity level
  • Blood tests including complete blood count, chemistries and liver function tests
  • Blood tests to check thyroid function
  • ECG in triplicate (3 ECGs will be done at least 5 minutes apart)
  • Review of all medications patient is taking including over-the-counter medicines, vitamins, dietary and herbal supplements
  • Monitoring of side effects –patients will be monitored for side effects for up to 30 days after last dose of study drug (gilteritinib or midostaurin).
  • ECG will be done in triplicate (3 ECGs will be done at least 5 minutes apart) before patient receives gilteritinib or midostaurin
  • Bone marrow aspiration and biopsy to assess response to treatment
  • Research blood samples if patient is receiving gilteritinib: 10 mL (approximately 2 teaspoons) of blood will be drawn and saved for future research
  • MUGA scan or ECHO to check heart function will be obtained using the same method as initial testing
  • ECG will be done in triplicate (3 ECGs will be done at least 5 minutes apart) before start of the second cycle of induction, then as clinically indicated
  • Bone marrow aspiration and biopsy to assess response to treatment. Some of the bone marrow sample will be sent for research for Minimal Residual Disease (MRD) analysis (measures the disease remaining after treatment) and repeat FLT3 testing. If unable to have the MRD sample sent for research, patient will receive no further treatment on this study. The remaining bone marrow sample will be stored for future research.

     

  • Research blood samples if patient is receiving gilteritinib: 10 mL (approximately 2 teaspoons) of blood will be drawn and saved for future research

In addition, if disease comes back, a sample of your bone marrow may be taken for future research (optional).