Gilteritinib + Ivosidenib/Enasidenib for Acute Myeloid Leukemia
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial tests a new drug combination to determine its safety and effectiveness in treating acute myeloid leukemia (AML) that has returned or is unresponsive to treatment. Researchers aim to find the optimal dose of gilteritinib (Xospata) combined with either ivosidenib (Tibsovo) or enasidenib (Idhifa) that minimizes side effects. This trial targets individuals with AML who have specific gene mutations in FLT3 and IDH1 or IDH2, confirmed by testing. Those with AML unresponsive to previous treatments and possessing these gene mutations may find this trial suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.
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.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research shows that gilteritinib, when used alone, is generally easy for patients to handle. In a study with 319 patients who had relapsed or hard-to-treat acute myeloid leukemia (AML), gilteritinib demonstrated a manageable safety profile. Patients experienced some side effects, but these were often mild and manageable. Similarly, enasidenib, a drug targeting specific gene mutations, has succeeded in patients with those mutations, showing good results.
For ivosidenib, another drug targeting similar gene mutations, studies have shown it works well when combined with gilteritinib. The safety information for ivosidenib also suggests it is generally easy for patients to handle, with side effects similar to those seen with enasidenib.
This trial is in its early stages, so researchers are still determining the best dose to keep side effects mild. The fact that gilteritinib is already approved by the FDA for other uses adds some confidence about its safety. However, since combining these drugs is new, researchers are closely monitoring to ensure safety for all participants.12345Why are researchers excited about this trial's treatments?
Researchers are excited about the combination treatments of gilteritinib with ivosidenib or enasidenib for Acute Myeloid Leukemia (AML) because they target cancer in a novel way. Most standard AML treatments, like chemotherapy, focus on eliminating rapidly dividing cells, which can affect healthy cells too. However, gilteritinib targets specific mutations in the FLT3 gene, while ivosidenib and enasidenib target IDH1 and IDH2 mutations, respectively. This precision approach could potentially reduce side effects and improve outcomes by directly interrupting cancer cell growth pathways, offering a more tailored and effective treatment option for patients with these mutations.
What evidence suggests that this trial's treatments could be effective for relapsed/refractory AML?
Research shows that gilteritinib alone can achieve a 37% remission rate in patients with relapsed and refractory acute myeloid leukemia (AML) who have FLT3 mutations. In this trial, one group of participants will receive a combination of gilteritinib and enasidenib, which targets a different mutation called IDH2. This combination might enhance treatment effectiveness because these drugs address different genetic changes causing AML. Studies have found that using FLT3 and IDH inhibitors like gilteritinib and enasidenib together has a modest success rate of 17% after other treatments have been tried. Another group in this trial will receive a combination of gilteritinib with ivosidenib, which targets IDH1 mutations. Combining gilteritinib with ivosidenib shows promise; when ivosidenib is used with another drug, it has resulted in complete remission for 51% of patients with IDH1 mutations. These drug combinations aim to address multiple mutation types in AML, potentially leading to better outcomes.14678
Who Is on the Research Team?
Eytan Stein, MD
Principal Investigator
Memorial Sloan Kettering Cancer Center
Are You a Good Fit for This Trial?
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
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive the combination of gilteritinib with ivosidenib or enasidenib in continuous 28-day cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Enasidenib
- Gilteritinib
- Ivosidenib
Enasidenib is already approved in United States, European Union for the following indications:
- Relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation
- Acute myeloid leukaemia (AML) with an isocitrate dehydrogenase 2 (IDH2) mutation
Find a Clinic Near You
Who Is Running the Clinical Trial?
Memorial Sloan Kettering Cancer Center
Lead Sponsor
Astellas Pharma US, Inc.
Industry Sponsor
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