Gilteritinib + Azacitidine for Acute Myeloid Leukemia

No longer recruiting at 140 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Astellas Pharma Global Development, Inc.

Must be taking: Azacitidine

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

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: Unknown

Duration: Up to 77 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment approach for individuals recently diagnosed with acute myeloid leukemia (AML), a cancer where the bone marrow produces abnormal white blood cells. The study compares the current standard treatment, azacitidine (Vidaza®), with a combination of azacitidine and an experimental drug, gilteritinib (Xospata), which aims to slow leukemia cell growth. The researchers aim to determine if the combination helps patients live longer. Suitable candidates for this trial have been diagnosed with AML and cannot receive intensive chemotherapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot take certain drugs that strongly affect liver enzymes or specific receptors unless they are absolutely necessary for your care. It's best to discuss your current medications with the trial 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 combining gilteritinib with azacitidine has been tested for safety in people with acute myeloid leukemia (AML). In these studies, most patients tolerated the combination well. However, like most treatments, side effects can occur. Some reports mention serious adverse reactions, but these are not common for everyone.

Azacitidine alone is already a standard treatment for some AML patients in the United States. Studies have demonstrated its effectiveness, but there are safety concerns. Most side effects are serious, and some have been fatal. However, these serious effects do not occur in everyone.

The trial's advanced phase indicates that earlier studies found the treatments safe enough to continue testing. Prospective participants should discuss specific risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Gilteritinib and Azacitidine for treating Acute Myeloid Leukemia (AML) because it offers a fresh approach compared to standard treatments like chemotherapy alone or Azacitidine by itself. Gilteritinib is a targeted therapy that specifically inhibits FLT3, a gene mutation often found in AML, which can help slow down the progression of the disease. When combined with Azacitidine, which enhances the body's ability to kill cancer cells, this duo could potentially offer more effective results than traditional options. This combination aims to improve survival rates and remission status, giving hope for better long-term outcomes for AML patients.

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

This trial will evaluate the effectiveness of different treatment combinations for acute myeloid leukemia (AML). Research has shown that combining gilteritinib and azacitidine, one of the treatment arms in this trial, may effectively treat AML. Studies have found that this combination leads to more patients achieving complete remission, meaning their cancer cells disappear, compared to using azacitidine alone, which is another treatment arm in this trial. Gilteritinib blocks a protein that helps cancer cells grow, especially in patients with a FLT3 gene mutation. In past cases, this treatment has helped many patients live longer. On its own, azacitidine has been effective in helping some AML patients live longer, with a response rate of 44%. Both treatments show promise in managing AML, offering hope for better outcomes. ^{1 4 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

Adults recently diagnosed with AML and a FLT3 gene mutation, who can't have standard chemo. They must be over 18 (or over 65 in some cases), not suitable for intensive chemotherapy due to age or health issues like heart failure, poor kidney function, or low performance status. Participants need functioning major organs and agree to contraception if of childbearing potential.

Inclusion Criteria

I am legally an adult where I live.

Subject must meet certain clinical laboratory test criteria

My blood or bone marrow tested positive for the FLT3 mutation.

Exclusion Criteria

I need to take certain medications along with my treatment.

Subject with mean Fridericia-corrected QT interval (QTcF) > 480 ms at screening

Subject has specific pulmonary function test results

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Safety Cohort

8 to 12 patients are enrolled to evaluate the safety and tolerability of ASP2215 given with azacitidine

4 weeks

Treatment

Patients receive ASP2215 plus azacitidine or azacitidine alone in 28-day cycles

Up to 77 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 77 months

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Gilteritinib

Trial Overview The trial is testing gilteritinib alone or combined with azacitidine versus azacitidine by itself in adults with AML who can't receive standard chemo. Gilteritinib targets the FLT3 protein to slow leukemia growth. Patients are randomly assigned to treatments, with a higher chance of receiving the combination therapy.

How Is the Trial Designed?

Group I: Safety Cohort: Gilteritinib + Azacitidine (AZA) Experimental Treatment 2 Interventions

Participants received 80 mg (2 tablets of 40 mg) of gilteritinib orally once daily for continuous 28-day cycles and 75 mg/m\^2 of AZA daily via subcutaneous injection or intravenous infusion for 7 days of each 28-day treatment cycle. Depending on the safety cohort data ,the decision to initiate the randomized trial at the targeted dose was made. After the end of treatment period, participants were followed up for 30- day follow up period. Participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death). Participants in long-term follow-up who were no longer receiving treatment were followed every 3 months for survival until the implementation of the final protocol version 13.0, at which time they were discontinued from the study, as further survival data were no longer needed.

Group II: Randomized Cohort: Gilteritinib + AZA Experimental Treatment 1 Intervention

Participants received 120 mg(3 tablets of 40 mg)of gilteritinib orally once daily for continuous 28-day cycles in combination with 75mg/m\^2 of AZA daily via subcutaneous injection or IV infusion for 7days of each 28-day treatment cycle until the participant no longer received clinical benefit from therapy in the opinion of the investigator,unacceptable toxicity occurred,or the participant met another treatment discontinuation criterion.After the end of treatment period,participants were followed up for 30-day follow up period.Participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment,EQ-5D-5L,remission status and survival (cause and date of death).Participants in long-term follow-up who were no longer receiving treatment were followed every 3months for survival until the implementation of the final protocol version 13.0, at which time they were discontinued from the study,as further survival data were no longer needed.

Group III: Randomized Cohort: AZA Experimental Treatment 2 Interventions

Participants received 75 mg/m\^2 of AZA daily via subcutaneous injection or intravenous infusion for 7 days of each 28-day treatment cycle until the participant no longer received clinical benefit from therapy in the opinion of the investigator, unacceptable toxicity occurred or the participant met another treatment discontinuation criterion. After the end of treatment period, participants were followed up for 30- day follow up period. Participants were allowed to enter the long-term follow-up period of up to 3 years for collection of subsequent AML treatment, EQ-5D-5L, remission status and survival (cause of death and date of death). Participants in long-term follow-up who were no longer receiving treatment were followed every 3 months for survival until the implementation of the final protocol version 13.0, at which time they were discontinued from the study, as further survival data were no longer needed.

Group IV: Randomized Cohort: Gilteritinib Active Control 1 Intervention

Participants received 120 mg (3 tablets of 40 mg) of gilteritinib orally once daily for continuous 28-day cycles until the participant no longer received clinical benefit from therapy in the opinion of the investigator, unacceptable toxicity occurred or the participant met another treatment discontinuation criterion. However, randomization to this arm was removed in protocol version 7.0. Participants previously randomized to this arm continued following treatment and assessments as outlined in the protocol.

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

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9793740/

Clinical Utility of Azacitidine in the Management of Acute ... The data suggest that oral AZA maintenance is an effective maintenance strategy to prolong survival in high-risk as well as favorable-risk AML ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2213048916300486

Clinical outcomes of AML patients treated with Azacitidine ... Median OS was 10.6 months in those receiving AZA as 1st line. Response (overall response rate 44%) had a significant impact on overall survival (p=<0.0001).

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2425/531542/Real-World-Treatment-Patterns-and-Outcomes-with

Real-World Treatment Patterns and Outcomes with Oral ... At 12 mo, estimated OS and rwRFS rates from Oral-AZA initiation were 88.2% (standard error [SE], 2.3) and 85.5% (SE, 2.5), respectively. Median ...

4. nature.com nature.com/articles/s41375-025-02730-3

Outcomes of patients treated with venetoclax plus ... The 5-year relative survival of patients with AML is ~32%, and survival rates are dependent on age at diagnosis. Patients <50 years of age have ...

5. healthtree.org healthtree.org/aml/community/articles/outcomes-oral-azacitidine-secondary-aml

Outcomes from Oral Azacitidine Maintenance Therapy AML-MRC patients who took oral azacitidine had a longer time in remission of 7.5 months, compared to the placebo group's 3.7 months. In ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40233158/

Real-world treatment patterns and outcomes with oral ... Rates of real-world relapse-free survival and overall survival at 12 months from oral-AZA initiation were 66.9% and 74.5%, respectively. During ...

7. hematologyadvisor.com hematologyadvisor.com/news/azacitidine-myelodysplastic-syndrome-mds-adverse-events-safety-concerns/

New Adverse Events Highlight Safety Concerns With ... Most AEs (95.78%) were classified as serious, and 40.87% resulted in death. Health professionals submitted nearly 90% of the reports, with the ...