Gilteritinib + Ivosidenib/Enasidenib for Acute Myeloid Leukemia

Recruiting at 6 trial locations

Overseen By Eytan Stein, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Investigational agents

Disqualifiers: Acute promyelocytic leukemia, Active infections, Significant cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

36 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Gilteritinib for treating Acute Myeloid Leukemia?

Gilteritinib has been shown to improve survival and response rates in patients with relapsed or refractory acute myeloid leukemia (AML) with FLT3 mutations, compared to standard chemotherapy. It is effective as a single-agent treatment and is well-tolerated, making it a valuable option for these patients. ^{1 2 3 4 5}

Is the combination of Gilteritinib and Ivosidenib/Enasidenib safe for treating acute myeloid leukemia?

Gilteritinib has been shown to be generally safe in humans, with common side effects including anemia (low red blood cell count), febrile neutropenia (fever with low white blood cell count), and thrombocytopenia (low platelet count). Serious but manageable side effects include differentiation syndrome (a potentially life-threatening condition), QT interval prolongation (heart rhythm changes), and pancreatitis (inflammation of the pancreas). Safety data for Ivosidenib and Enasidenib are not provided in the available research. ^{1 2 3 4 6}

What makes the drug combination of Gilteritinib, Ivosidenib, and Enasidenib unique for treating acute myeloid leukemia?

This drug combination is unique because it targets specific genetic mutations in acute myeloid leukemia, such as FLT3 and IDH mutations, using oral medications that are more convenient and potentially less toxic than traditional chemotherapy. Gilteritinib is a potent FLT3 inhibitor, while Ivosidenib and Enasidenib target IDH1 and IDH2 mutations, respectively, offering a personalized approach to treatment. ^{1 2 3 4 6}

What is the purpose of this trial?

The researchers are doing this study to see if the combination of gilteritinib with ivosidenib or enasidenib is a safe and effective treatment for people with relapsed/refractory AML with FLT3/IDH1 or FLT3/IDH2 gene mutations. The researchers will also look for the highest dose of the combination of gilteritinib with ivosidenib or enasidenib that causes few or mild side effects. When the highest safe dose is found, they will test that dose in new groups of participants.

Research Team

Eytan Stein, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults over 18 with relapsed or refractory Acute Myeloid Leukemia (AML) and specific gene mutations (FLT3/IDH1 or FLT3/IDH2). They must be able to follow the study plan, have adequate organ function, and not be pregnant. Men and women must agree to use birth control. Exclusions include uncontrolled infections, severe leukemia complications, heart issues, absorption problems, certain neurological diseases, and those on other cancer trials.

Inclusion Criteria

My tests show FLT3 and IDH mutations in my recent relapse.

My kidney function is good, with a creatinine clearance rate of at least 30 mL/min or my serum creatinine is less than 2.0.

I have had a stem cell transplant for my AML.

Exclusion Criteria

I have a history of a brain infection called PML.

I have an ongoing serious infection that isn't under control.

Patient on any other investigational anti-cancer agents

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the combination of gilteritinib with ivosidenib or enasidenib in continuous 28-day cycles

1 year

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Enasidenib
• Gilteritinib
• Ivosidenib

Trial Overview The trial is testing if combining gilteritinib with ivosidenib or enasidenib is safe and effective for AML patients with certain genetic mutations. It aims to find the highest dose that causes few side effects before using this dose in new participant groups.

Participant Groups

Group I: gilteritinib + ivosidenib (Cohort 1) Experimental Treatment 2 Interventions

Each patient will take the combination of gilteritinib/ ivosidenib (Cohort 1) , daily, in continuous 28-day cycles at the dose level that they are assigned.

Group II: gilteritinib + enasidenib (Cohort 2) Experimental Treatment 2 Interventions

Each patient will take the combination of gilteritinib/enasidenib (Cohort 2) daily, in continuous 28-day cycles at the dose level that they are assigned.

Enasidenib is already approved in United States, European Union for the following indications:

Approved in United States as Idhifa for:

• Relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation

Approved in European Union as Idhifa for:

• Acute myeloid leukaemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Astellas Pharma US, Inc.

Industry Sponsor

Trials

90

Recruited

12,900+

Naoki Okamura

Astellas Pharma US, Inc.

Chief Executive Officer since 2023

Not available

Tadaaki Taniguchi

Astellas Pharma US, Inc.

Chief Medical Officer since 2023

MD, PhD

Findings from Research

In a phase 3 trial involving 371 patients with relapsed or refractory FLT3-mutated acute myeloid leukemia (AML), gilteritinib significantly improved overall survival compared to salvage chemotherapy, with a median survival of 9.3 months versus 5.6 months.

Gilteritinib also led to higher rates of complete remission (21.1% vs. 10.5%) and had fewer severe adverse events compared to chemotherapy, indicating it is a safer and more effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. Perl, AE., Martinelli, G., Cortes, JE., et al.[2023]

Gilteritinib fumarate is an effective and well-tolerated treatment for patients with relapsing or refractory FLT3-positive acute myeloid leukemia, showing promise in managing the disease with lower toxicity compared to earlier treatments.

The drug's oral formulation makes it suitable for a wide range of patients, including elderly and frail individuals, allowing for outpatient treatment that reduces hospitalization risks and costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy. Bocchia, M., Carella, AM., Mulè, A., et al.[2022]

Gilteritinib significantly improves overall survival and response rates in adults with relapsed or refractory acute myeloid leukaemia (AML) with FLT3 mutations, as demonstrated in the phase III ADMIRAL trial.

While gilteritinib is effective, it can cause serious side effects like anaemia and febrile neutropenia, but these are generally manageable with dose adjustments, highlighting the importance of monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib: A Review in Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukaemia. Kang, C., Blair, HA.[2021]

In a phase IB study involving 80 participants with newly diagnosed FLT3-mutated acute myeloid leukemia (AML), gilteritinib combined with intensive chemotherapy achieved a high composite complete response rate of 89%, indicating strong efficacy in this patient population.

Gilteritinib was well-tolerated as both part of the chemotherapy regimen and as maintenance therapy, with a median overall survival time of 46.1 months, suggesting it is a safe and effective treatment option for patients with FLT3-mutant AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib in Combination With Induction and Consolidation Chemotherapy and as Maintenance Therapy: A Phase IB Study in Patients With Newly Diagnosed AML. Pratz, KW., Cherry, M., Altman, JK., et al.[2023]

Gilteritinib fumarate is a highly selective oral FLT3 inhibitor that has shown significant efficacy in treating relapsed or refractory FLT3-mutated acute myeloid leukemia (AML), with clinical trials indicating higher response rates and longer overall survival compared to traditional salvage chemotherapy.

The drug was well tolerated in clinical trials, with dose-proportional plasma concentrations observed at doses ranging from 20 to 450 mg/day, supporting its safety profile for patients in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological and clinical profile of gilteritinib (Xospata® tablets 40 mg), a therapeutic agent for relapsed or refractory FLT3-mutated acute myeloid leukemia]. Mori, M., Hidaka, K.[2021]

Gilteritinib, an FLT3 inhibitor approved by the FDA for relapsed or refractory acute myeloid leukemia, showed a 21% complete remission rate and a median overall survival of 9.3 months compared to 5.6 months with standard chemotherapy, indicating its efficacy in improving patient outcomes.

The treatment comes with safety warnings for serious conditions like differentiation syndrome and QT prolongation, necessitating careful monitoring of patients' heart rhythms and blood chemistry during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Gilteritinib for Relapsed or Refractory Acute Myeloid Leukemia with a FLT3 Mutation. Pulte, ED., Norsworthy, KJ., Wang, Y., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Gilteritinib: A Review in Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukaemia. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Gilteritinib in Combination With Induction and Consolidation Chemotherapy and as Maintenance Therapy: A Phase IB Study in Patients With Newly Diagnosed AML. [2023]

5. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacological and clinical profile of gilteritinib (Xospata® tablets 40 mg), a therapeutic agent for relapsed or refractory FLT3-mutated acute myeloid leukemia]. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Gilteritinib for Relapsed or Refractory Acute Myeloid Leukemia with a FLT3 Mutation. [2023]