Gilteritinib vs Midostaurin for Acute Myeloid Leukemia

Not currently recruiting at 43 trial locations

Overseen By Soumya Chappidi, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: PrECOG, LLC.

Must not be taking: CYP3A inducers, P-gp inducers

Disqualifiers: M3 AML, CNS leukemia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two oral drugs, gilteritinib and midostaurin, to determine which works better when combined with standard chemotherapy for FLT3 acute myeloid leukemia (AML). Gilteritinib aims to stop leukemia cells from producing a protein that aids their growth, while midostaurin blocks several proteins, including the one targeted by gilteritinib. The trial seeks individuals newly diagnosed with FLT3-mutated AML who have not yet received treatment for this condition. Participants will receive one of these drugs alongside chemotherapy to identify which combination most effectively controls their leukemia. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take drugs that strongly affect certain liver enzymes (CYP3A and P-gp), so check with your doctor about your specific medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that gilteritinib is generally well-tolerated by patients with relapsed or refractory acute myeloid leukemia (AML). About 3% of patients experienced differentiation syndrome, a side effect where cells mature too quickly. The FDA has already approved gilteritinib for certain AML cases, indicating that its safety is well understood.

Research on midostaurin has shown it is also well-tolerated when used with chemotherapy. The FDA has approved this drug for treating a type of AML called FLT3, confirming its safety profile.

Overall, both gilteritinib and midostaurin have been used in patients with AML, and their safety has been studied. This suggests they should be relatively safe for most people, but like any treatment, side effects can occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about gilteritinib as a treatment for acute myeloid leukemia (AML) because it targets FLT3 mutations, which are common in AML patients, more specifically and effectively than many existing options. Unlike standard treatments like midostaurin, which also targets FLT3 but less selectively, gilteritinib has shown promise in overcoming resistance and improving outcomes due to its potent and selective inhibition. This specificity could lead to better results for patients, offering a potential new line of attack against aggressive leukemia cells.

What evidence suggests that this trial's treatments could be effective for FLT3 AML?

This trial will compare Gilteritinib and Midostaurin for treating acute myeloid leukemia (AML). Research has shown that Gilteritinib, which participants in this trial may receive, can benefit patients with FLT3-mutated AML. Studies have demonstrated improved survival rates and treatment responses with Gilteritinib compared to other options for AML that has returned after treatment, although it is not yet approved for newly diagnosed cases. Meanwhile, Midostaurin, another treatment option in this trial, is already approved for treating FLT3 AML and has been shown to increase survival when used with standard chemotherapy. Specifically, one study found that 51.4% of patients using Midostaurin with chemotherapy were alive after four years. Both drugs target the FLT3 protein, which aids leukemia cell growth, potentially enhancing chemotherapy effectiveness. ^{2 3 6 7 8}

Who Is on the Research Team?

Selena Luger, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

Adults aged 18-70 with previously untreated FLT3 mutated Acute Myeloid Leukemia (AML) who have good organ function and no severe heart conditions or other cancers. They must not be pregnant, agree to use contraception, and can't have had certain treatments for related diseases within the last 21 days.

Inclusion Criteria

I do not have another cancer that could affect this treatment's results.

I haven't taken any hypomethylating agents in the last 21 days.

I can care for myself but may not be able to do heavy physical work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Participants receive standard chemotherapy of daunorubicin and cytarabine, and are randomized to receive either gilteritinib or midostaurin. Bone marrow aspirate and biopsy are done on Day 21 and after Induction to assess response.

3 months

Multiple visits (in-person)

Consolidation

Participants with a complete response proceed to consolidation chemotherapy with high-dose cytarabine and either gilteritinib or midostaurin. Bone marrow aspirate and biopsy are done after the first cycle of consolidation.

3 months

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of overall survival and event-free survival.

68 months

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Daunorubicin
• Gilteritinib
• Midostaurin

Trial Overview The trial is testing whether gilteritinib or midostaurin is more effective when combined with standard chemotherapy drugs daunorubicin and cytarabine in treating AML. Gilteritinib is investigational in this context while midostaurin is FDA-approved for FLT3 AML.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 3 Interventions

Induction: Daunorubicin, cytarabine and gilteritinib. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and gilteritinib.

Group II: Arm B Active Control 3 Interventions

Induction: Daunorubicin, cytarabine and midostaurin. Depending on response, second cycle of Induction may be given. Consolidation: High-dose cytarabine and midostaurin.

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

Approved in United States as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Meningeal leukemia

Approved in European Union as Depocyt for:

• Lymphomatous meningitis

Approved in Canada as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia

Who Is Running the Clinical Trial?

PrECOG, LLC.

Lead Sponsor

Trials

19

Recruited

8,000+

Astellas Pharma Inc

Industry Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Published Research Related to This Trial

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]

Midostaurin, when combined with standard chemotherapy (cytarabine and daunorubicin), significantly improves event-free survival, disease-free survival, and overall survival in patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML), based on a phase III trial.

The treatment with midostaurin is considered safe, showing no significant difference in overall toxicity compared to placebo, although it was associated with a higher incidence of grade 3 to 5 anemia and rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midostaurin in Combination With Standard Chemotherapy for Treatment of Newly Diagnosed FMS-Like Tyrosine Kinase 3 (FLT3) Mutation-Positive Acute Myeloid Leukemia. Kim, M., Williams, S.[2019]

Midostaurin, a multikinase inhibitor, was found to have a manageable safety profile in a study of 103 patients with FLT3 mutation-positive acute myeloid leukemia, with no new safety events reported during treatment.

The treatment showed promising outcomes, including high rates of transplant success and low relapse rates during maintenance therapy, indicating its efficacy when combined with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated safety of midostaurin plus chemotherapy in newly diagnosed FLT3 mutation-positive acute myeloid leukemia: the RADIUS-X expanded access program. Roboz, GJ., Strickland, SA., Litzow, MR., et al.[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]

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]

Midostaurin is an oral Type III receptor tyrosine kinase inhibitor that effectively targets FLT3 mutations in acute myeloid leukemia (AML), showing robust anti-blast responses in relapsed/refractory patients and potentially bridging them to transplant.

While generally well tolerated as a single agent, midostaurin's hematologic toxicity increases when combined with standard chemotherapy, but it may prolong survival in patients with FLT3-ITD mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Midostaurin: an emerging treatment for acute myeloid leukemia patients. Gallogly, MM., Lazarus, HM.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40839405/

Gilteritinib in FLT3-mutated acute myeloid leukemia: A real- ... The median overall survival (OS) for the entire cohort was 11.0 months, with estimated OS rates of 46.8% at 1 year and 28.5% at 3 years. Sixty ...

2. ashpublications.org ashpublications.org/bloodadvances/article/8/21/5590/517770/Outcomes-with-single-agent-gilteritinib-for

Outcomes with single-agent gilteritinib for relapsed or ... Complete remission (CR) was achieved in 21%, and CR with incomplete recovery (CRi) in a further 9%. Remission rates were lower for patients with ...

3. xospatahcp.com xospatahcp.com/efficacy

ADMIRAL Trial: XOSPATA® (gilteritinib) Overall Survival Discover efficacy data for overall survival with XOSPATA in the treatment of relapsed or refractory FLT3m+ AML. See Important Safety Information including ...

4. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.70055

Gilteritinib in FLT3‐mutated acute myeloid leukemia: A real ... Among 46 patients (22.4%) who relapsed after allo-SCT, gilteritinib treatment yielded an overall response rate (ORR) of 54.3%, a median OS of ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025017926

AML-1203: Efficacy of Gilteritinib Versus Salvage ... In this metaanalysis, gilteritinib significantly improved OS and ORR compared with salvage chemotherapy in FLT3-mutated AML. Additionally, single-arm studies of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8506653/

FDA Approval Summary: Gilteritinib for relapsed or refractory ... The primary safety population (n=319) included patients with R/R AML who received 120 mg gilteritinib, regardless of FLT3 status (Table 1).

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666636722018322

Outcomes in Patients with FLT3-Mutated Relapsed ... Gilteritinib as post-transplantation maintenance therapy had a stable safety and tolerability profile and was associated with low relapse rates.

8. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6079/527220/Efficacy-and-Safety-of-Gilteritinib-Based-Therapy

Efficacy and Safety of Gilteritinib-Based Therapy Combinated ... The gilteritinib-based combination therapy demonstrates a high composite complete remission rate, MRD negativity rate, and long patients' survival in treating ...