Iadademstat + Gilteritinib for Acute Myeloid Leukemia

(FRIDA Trial)

Recruiting at 15 trial locations

Overseen By Mónica Reale-Vidal, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Oryzon Genomics S.A.

Must not be taking: KDM1A/LSD1 inhibitors

Disqualifiers: Acute promyelocytic leukemia, BCR-ABL-positive leukemia, uncontrolled infections, others

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Iadademstat is being studied as a treatment for subjects with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) with FMS-like tyrosine kinase mutation (FLT3 mut+). During the trial, iadademstat will be given in combination with gilteritinib, a drug that is already approved to treat patients with FLT3-mutated R/R AML.

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 have had treatment with iadademstat before, and any treatment with KDM1A/LSD1 inhibitors must have ended at least 3 weeks before starting the trial. Also, you cannot have taken any investigational products within 3 weeks prior to the trial.

What data supports the effectiveness of the drug Gilteritinib for treating Acute Myeloid Leukemia?

Gilteritinib has been shown to improve survival in patients with relapsed or refractory acute myeloid leukemia (AML) with a specific mutation (FLT3). In studies, it led to higher rates of complete remission and longer survival compared to standard chemotherapy. ^{1 2 3 4 5}

Is the combination of Iadademstat and Gilteritinib safe for treating acute myeloid leukemia?

Gilteritinib, also known as Xospata, has been approved for treating acute myeloid leukemia with a specific mutation and has a known safety profile. Common side effects include anemia, fever, and low platelet counts, while serious risks include differentiation syndrome, brain-related issues, heart rhythm changes, and pancreatitis. Safety measures include regular monitoring of heart and blood health, and it is important to use contraception during treatment due to potential risks to unborn babies. ^{2 3 6 7 8}

What makes the drug combination of Iadademstat and Gilteritinib unique for treating acute myeloid leukemia?

The combination of Iadademstat and Gilteritinib is unique because it targets acute myeloid leukemia with a specific FLT3 mutation, using Gilteritinib's ability to inhibit the FLT3 enzyme, which is involved in cancer cell growth, and Iadademstat's potential to enhance this effect, offering a novel approach compared to standard chemotherapy. ^{2 3 7 9 10}

Research Team

Mónica Reale-Vidal, MD

Principal Investigator

Oryzon Genomics

Eligibility Criteria

This trial is for adults with Acute Myeloid Leukemia (AML) that has returned or hasn't responded to treatment, and they must have specific FLT3 mutations. They should be able to perform daily activities with ease to moderate difficulty, have a life expectancy of at least 3 months, and normal liver and kidney function. Women must not be pregnant and use contraception; men agree to use barrier contraception.

Inclusion Criteria

I can take care of myself and perform daily activities.

Life expectancy of at least 3 months in the opinion of the investigator

My liver and kidney functions are normal.

Exclusion Criteria

I cannot take gilteritinib according to its usage instructions.

Pregnant or lactating women

I haven't had major surgery or radiation therapy in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and emerging activity of iadademstat and gilteritinib combination, and determine the pharmacologically-active dose

Up to 26 days

Expansion

Evaluate the activity of iadademstat in combination with gilteritinib at the selected dose in patients with FLT3-mutated R/R AML

Up to 18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 months

Treatment Details

Interventions

• Gilteritinib
• Iadademstat

Trial Overview The study tests Iadademstat in combination with Gilteritinib, an approved drug for AML with FLT3 mutation. It's aimed at patients whose AML has relapsed or is refractory. The goal is to see if adding Iadademstat can improve outcomes compared to using Gilteritinib alone.

Participant Groups

Group I: Active arm Experimental Treatment 2 Interventions

iadademstat and gilteritinib

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

Approved in United States as Xospata for:

• Acute myeloid leukemia (AML) with FLT3 mutation

Approved in European Union as Xospata for:

• Acute myeloid leukemia (AML) with FLT3 mutation

Approved in Japan as Xospata for:

• Acute myeloid leukemia (AML) with FLT3 mutation

Who Is Running the Clinical Trial?

Oryzon Genomics S.A.

Lead Sponsor

Trials

5

Recruited

350+

Findings from Research

Gilteritinib is a newly approved second-generation FLT3 inhibitor specifically designed for treating relapsed or refractory acute myeloid leukemia (AML) in patients with FLT3 mutations, which are found in about one-third of AML cases.

This treatment targets the FLT3 mutation, which is associated with poor prognosis due to increased tumor growth and reduced cell differentiation, potentially improving outcomes for patients with this challenging form of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib: A Novel FLT3 Inhibitor for Relapsed/Refractory Acute Myeloid Leukemia. Marjoncu, D., Andrick, B.[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]

In a phase IB study involving 80 participants with newly diagnosed FLT3-mutated acute myeloid leukemia (AML), gilteritinib combined with intensive chemotherapy achieved a high composite complete response rate of 89%, indicating strong efficacy in this patient population.

Gilteritinib was well-tolerated as both part of the chemotherapy regimen and as maintenance therapy, with a median overall survival time of 46.1 months, suggesting it is a safe and effective treatment option for patients with FLT3-mutant AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib in Combination With Induction and Consolidation Chemotherapy and as Maintenance Therapy: A Phase IB Study in Patients With Newly Diagnosed AML. Pratz, KW., Cherry, M., Altman, JK., et al.[2023]

In a phase 3 trial involving 371 patients with relapsed or refractory FLT3-mutated acute myeloid leukemia (AML), gilteritinib significantly improved overall survival compared to salvage chemotherapy, with a median survival of 9.3 months versus 5.6 months.

Gilteritinib also led to higher rates of complete remission (21.1% vs. 10.5%) and had fewer severe adverse events compared to chemotherapy, indicating it is a safer and more effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. Perl, AE., Martinelli, G., Cortes, JE., et al.[2023]

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]

Gilteritinib has been approved in the EU as a monotherapy for adult patients with relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation, showing a significant improvement in overall survival (9.3 months) compared to salvage chemotherapy (5.6 months) in a phase III study with 371 participants.

The safety profile of gilteritinib is considered manageable, with common side effects including increases in liver enzymes and creatine phosphokinase, as well as gastrointestinal and general symptoms like fatigue and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Gilteritinib (Xospata) for the Treatment of Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an FLT3 Mutation. Tzogani, K., Røshol, H., Olsen, HH., et al.[2021]

Gilteritinib is an effective oral treatment for acute myeloid leukaemia (AML) with FLT3 mutations, approved in both Japan and the USA for patients with relapsed or refractory cases.

It works by inhibiting FLT3 signaling, leading to apoptosis in cancer cells, and also targets ALK mutations, reducing tumor cell proliferation, showcasing its dual mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib: First Global Approval. Dhillon, S.[2020]

In a real-life study of 17 patients with FLT3-positive relapsed/refractory acute myeloid leukemia (AML) treated with gilteritinib, the overall response rate was an impressive 100%, indicating its strong efficacy.

However, the study also highlighted safety concerns, as common adverse events included anemia and hypokalemia, with patients experiencing peripheral edema having a significantly higher risk of death compared to those without it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gilteritinib (XOSPATA®) in Turkey: Early Access Program Results. Dogu, MH., Tekgunduz, AIE., Deveci, B., et al.[2023]

Gilteritinib fumarate is an effective and well-tolerated treatment for patients with relapsing or refractory FLT3-positive acute myeloid leukemia, showing promise in managing the disease with lower toxicity compared to earlier treatments.

The drug's oral formulation makes it suitable for a wide range of patients, including elderly and frail individuals, allowing for outpatient treatment that reduces hospitalization risks and costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy. Bocchia, M., Carella, AM., Mulè, A., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Gilteritinib: A Novel FLT3 Inhibitor for Relapsed/Refractory Acute Myeloid Leukemia. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Gilteritinib for Relapsed or Refractory Acute Myeloid Leukemia with a FLT3 Mutation. [2023]

3. Japan 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]. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Gilteritinib in Combination With Induction and Consolidation Chemotherapy and as Maintenance Therapy: A Phase IB Study in Patients With Newly Diagnosed AML. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. [2023]

6. France pubmed.ncbi.nlm.nih.gov

Gilteritinib: A Review in Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukaemia. [2021]

7. England pubmed.ncbi.nlm.nih.gov

The European Medicines Agency Review of Gilteritinib (Xospata) for the Treatment of Adult Patients with Relapsed or Refractory Acute Myeloid Leukemia with an FLT3 Mutation. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Gilteritinib: First Global Approval. [2020]

9. Italy pubmed.ncbi.nlm.nih.gov

Gilteritinib (XOSPATA®) in Turkey: Early Access Program Results. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy. [2022]