Gilteritinib for Acute Myeloid Leukemia

No longer recruiting at 147 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Astellas Pharma Global Development, Inc.

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

Disqualifiers: APL, BCR-ABL leukemia, CNS leukemia, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: Variable (up to 885 days for ASP2215, up to 217 days for salvage chemotherapy)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a drug called Gilteritinib for individuals with acute myeloid leukemia (AML) who have a FLT3 gene mutation and whose cancer has returned or did not respond to initial treatment. The study compares Gilteritinib to traditional chemotherapy to determine which treatment better helps patients live longer and achieve remission, where cancer is not detectable. Suitable candidates for this trial have AML with the FLT3 mutation and have not succeeded with their first round of treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications that strongly affect liver enzymes or specific receptors, unless they are absolutely essential for your care. It's best to discuss your current medications with the study team to see if any adjustments are needed.

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

Research has shown that gilteritinib, a treatment for certain types of acute myeloid leukemia (AML), is generally well-tolerated. It is already approved for patients with FLT3-mutant AML, indicating its safety. In earlier studies, researchers tested gilteritinib to find the safest dose, determining the best amount to administer while managing side effects. Some participants experienced side effects, but the medication's benefits in treating AML were significant. Overall, the available safety information suggests that gilteritinib is a good option for those with this specific leukemia mutation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute myeloid leukemia?

Gilteritinib is unique because it specifically targets and inhibits FLT3, a common mutation found in acute myeloid leukemia (AML) cells. This is different from standard treatments like chemotherapy, which broadly attack all rapidly dividing cells and often come with significant side effects. By focusing on the FLT3 mutation, gilteritinib offers a more targeted approach with the potential for fewer side effects and improved outcomes for patients with FLT3-mutated AML. Researchers are excited because this targeted approach could significantly enhance treatment efficacy compared to traditional chemotherapy regimens.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research has shown that Gilteritinib, which participants in this trial may receive, may effectively treat FLT3-mutated acute myeloid leukemia (AML). In one study, patients taking Gilteritinib lived for a median of 11 months, with almost half surviving beyond a year. Complete remission, meaning no signs of cancer, was achieved in 21% of patients, and 9% showed partial improvement. Another study found that Gilteritinib led to better survival and response rates compared to standard chemotherapy. These findings suggest Gilteritinib could be a strong option for those whose AML has returned or is resistant to other treatments. Meanwhile, participants in another arm of this trial will receive salvage chemotherapy, which includes treatments like LoDAC, azacitidine, MEC, or FLAG-IDA. ^{6 7 8 9 10}

Who Is on the Research Team?

Executive Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with relapsed or refractory Acute Myeloid Leukemia (AML) that have a specific mutation called FLT3. They should not have had success with first-line AML therapy and must be physically able to handle the treatments, as indicated by an ECOG performance status of 2 or less. Women of childbearing age must agree to use effective contraception and not breastfeed.

Inclusion Criteria

I am eligible for a specific follow-up chemotherapy.

Participant must meet specific clinical laboratory test criteria

I have been diagnosed with acute myeloid leukemia, either primary or following MDS.

Exclusion Criteria

Participant has clinically significant abnormality of coagulation profile

Participant has any condition which makes the Participant unsuitable for study participation

I have active leukemia in my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants receive ASP2215 or salvage chemotherapy in continuous 28-day cycles

Variable (up to 885 days for ASP2215, up to 217 days for salvage chemotherapy)

Follow-up

Participants are monitored for safety and effectiveness after treatment discontinuation

30 days

1 visit (telephone contact)

Long-term Follow-up

Long-term follow-up every 3 months up to 3 years from the participant's end-of-treatment visit

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• ASP2215
• Azacitidine
• FLAG-IDA
• gilteritinib
• LoDAC
• MEC

Trial Overview The study tests ASP2215 against standard salvage chemotherapy in patients whose AML has returned after treatment or didn't respond to initial therapy. It aims to see if ASP2215 can improve overall survival, event-free survival, and rates of complete remission compared to existing chemotherapy options.

How Is the Trial Designed?

Group I: Gilteritinib Experimental Treatment 1 Intervention

Participants received 120 mg dose (3 tablets of 40 mg) orally once a day in continuous 28-day cycles, at least 2 hours after or 1 hour before food. Gilteritinib treatment continued until participants met one of the treatment discontinuation criteria.

Group II: Salvage Chemotherapy Active Control 4 Interventions

Participants received chemotherapy in 28-day cycles. Participants on Low-Dose Cytarabine (LoDAC) received 20 mg of cytarabine twice daily by subcutaneous (SC) or intravenous (IV) injection for 10 days. Participants on azacitidine received 75 mg/m\^2 daily by SC or IV injection for 7 days. Participants on LoDAC or azacitidine treatment continued until they met discontinuation criteria. Participants on MEC chemotherapy received mitoxantrone 8 mg/m\^2 daily by IV for 5 days, etoposide 100 mg/m\^2 daily by IV for 5 days and cytarabine 1000 mg/m\^2 daily by IV for 5 days (days 1-5). Participants on FLAG-IDA chemotherapy received G-CSF 300 μg/m\^2 daily by SC/IV for 5 days (days 1-5), fludarabine 30 mg/m\^2 daily by IV for 5 days (days 2-6), cytarabine 2000 mg/m\^2 daily by IV for 5 days (days 2-6) and idarubicin 10 mg/m\^2 daily by IV for 3 days (days 2-4). Participants receiving MEC or FLAG-IDA received 1 cycle of therapy and were assessed for response on or after day 15.

Who Is Running the Clinical Trial?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

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. 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 ...

4. 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 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02927262

NCT02927262 | A Study of ASP2215 (Gilteritinib ... The purpose of this study was to compare relapse-free survival (RFS) between participants with FMS-like tyrosine kinase 3 (FLT3) / internal tandem duplication ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11523226/

Efficacy and safety of second‑generation FLT3 inhibitors in ... These findings suggest that second-generation FLT3 inhibitors can improve the overall survival of patients with AML.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02014558

NCT02014558 | Dose Escalation Study Investigating the ... The objective of this study was to assess the safety and tolerability, including the maximum tolerated dose, of gilteritinib in participants with relapsed ...

8. asco.org asco.org/abstracts-presentations/ABSTRACT164597

Pharmacokinetics and pharmacodynamics of gilteritinib in ... Background: Gilteritinib, also known as ASP2215, is a selective FLT3 inhibitor in development for the treatment of acute myeloid leukemia (AML).

9. aml-hub.com aml-hub.com/medical-information/post-marketing-pharmacovigilance-study-of-gilteritinib-and-midostaurin-from-the-faers-database

Post-marketing pharmacovigilance study of gilteritinib and ... The FLT3 inhibitors midostaurin and gilteritinib are approved for treatment of patients with FLT3-mutant R/R AML. However, real-world safety ...

10. newsroom.astellas.us newsroom.astellas.us/2017-06-22-The-Lancet-Oncology-Publishes-Anti-Leukemic-Activity-and-Safety-Data-for-gilteritinib-in-Relapsed-Refractory-Acute-Myeloid-Leukemia

The Lancet Oncology Publishes Anti-Leukemic Activity and ... The Lancet Oncology Publishes Anti-Leukemic Activity and Safety Data for gilteritinib in Relapsed/Refractory Acute Myeloid Leukemia. Data ...