What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML), particularly chemotherapy (e.g., Vyxeos) and FLT3 inhibitors (e.g., gilteritinib), are associated with several side effects. Chemotherapy often leads to cytopenias, infections, gastrointestinal toxicity, fatigue, and potential organ-specific toxicities. FLT3 inhibitors can cause cytopenias, liver enzyme abnormalities, and gastrointestinal symptoms. Combining these treatments may increase the risk and severity of these side effects, requiring careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myeloid Leukemia (AML) that involve chemotherapy and FLT3 inhibition. Vyxeos (daunorubicin and cytarabine) is a liposomal formulation of chemotherapy specifically approved for the treatment of newly diagnosed therapy-related AML or AML with myelodysplasia-related changes. Gilteritinib, an FLT3 inhibitor, is approved for the treatment of relapsed or refractory AML with a FLT3 mutation. These approvals highlight the FDA's recognition of the importance of combining targeted therapies like FLT3 inhibitors with traditional chemotherapy to improve outcomes in AML patients.

What other types of research exist?

Promising novel alternatives for AML treatment in 2024 include alvocidib (flavopiridol), which has shown encouraging results in clinical trials for relapsed/refractory and newly diagnosed non-favorable risk AML patients. Additionally, venetoclax, particularly in combination with other agents, has demonstrated preliminary efficacy in elderly patients with IDH mutations. These alternatives offer new mechanisms of action and potential benefits for AML patients.

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Tyrosine Kinase Inhibitor

Vyxeos + Gilteritinib for Acute Myeloid Leukemia

Phase 1

Recruiting

Led By Onyee Chan, MD

Research Sponsored by H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

FLT3 testing must be confirmed at the time of disease relapse

Eastern Cooperative Oncology Group (ECOG) performance status ≤2

Must not have

Patients must not have evidence of GI tract abnormalities that would alter the absorption of oral medications

Patients with documented central nervous system involvement of AML

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial combines Vyxeos, a chemotherapy drug, and Gilteritinib, a targeted therapy, for patients with a specific type of acute myeloid leukemia. Vyxeos attacks cancer cells using a combination of drugs, while Gilteritinib blocks a protein that helps these cancer cells grow. The goal is to see if this combination can help patients who have not responded to other treatments.

Who is the study for?

This trial is for adults with a specific mutation in their leukemia cells (FLT3) who have seen their disease return or not respond to treatment. They must be able to perform daily activities with some limitations, take oral meds, and use effective birth control if applicable. People can't join if they've had certain complications like severe graft versus host disease after a stem cell transplant or AML progression on gilteritinib.

What is being tested?

The study tests combining Vyxeos (chemotherapy) and Gilteritinib (targeted therapy) in patients whose acute myeloid leukemia has returned or resisted treatment. It involves initial intense therapy followed by maintenance using Gilteritinib alone for those ineligible for stem cell transplant.

What are the potential side effects?

Possible side effects include heart problems due to Vyxeos, gastrointestinal issues affecting how well the body absorbs Gilteritinib, liver and kidney function changes, blood count abnormalities leading to increased infection risk, fatigue, and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My FLT3 test was positive at the time my disease came back.

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I can take care of myself but might not be able to do heavy physical work.

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My AML has FLT3 mutations and has not responded to at least one treatment.

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I have received a limited amount of a specific chemotherapy drug.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My digestive system can properly absorb medications.

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My AML has spread to my brain or spinal cord.

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My AML worsened despite being on gilteritinib.

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My white blood cell count is high, but I can use medication to manage it until treatment starts.

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I have severe graft versus host disease and am not taking steroids for it.

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I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

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I haven't had major surgery in the last two weeks or have fully recovered from one done more than two weeks ago.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum Tolerated Dose (MTD)

Secondary study objectives

Complete Remission Rate

Event free survival (EFS)

Overall survival (OS)

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Dose Expansion ArmExperimental Treatment2 Interventions

Participants will receive intravenous Vyxeos on days 1, 3 and 5 and Gilteritinib will be given on days 6-19 of induction therapy in the dose determined in the dose escalation arm.

Group II: Dose Escalation ArmExperimental Treatment2 Interventions

Participants will receive intravenous Vyxeos on days 1, 3 and 5 and Gilteritinib will be given on days 6-19 of induction therapy. The induction and reinduction dose of Vyxeos is 44mg/m2 daunorubicin and 100mg/m2 of cytarabine with each infusion. Dose level 1: Vyxeos + 120 mg Gilertinib In the event of a dose-limiting toxicity (DLT) at the initial dose level, a dose level minus (-) 1 is permitted Dose Level -1: Vyxeos + 80 mg Gilertinib

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Gilteritinib

2014

Completed Phase 2

~660

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Acute Myeloid Leukemia (AML) include chemotherapy and FLT3 inhibitors. Chemotherapy agents, such as Vyxeos, work by damaging the DNA of rapidly dividing cells, including AML cells, leading to their death. FLT3 inhibitors, like Gilteritinib, specifically target mutations in the FLT3 gene, which are common in AML, blocking the signaling pathways that promote the growth and survival of leukemic cells. These mechanisms are important for AML patients as they help in selecting targeted therapies that can effectively reduce the leukemic cell burden and improve treatment outcomes.

Progress in the problem of relapsed or refractory acute myeloid leukemia.