Recruiting Trials for New Therapy Regimen for AML Patients

Acute myeloid leukemia (AML) is an aggressive form of blood cancer that originates from mutations in immature white blood cells in the bone marrow, ​​disrupting normal blood cell production. The estimated number of new cases of AML in 2024 is 20,800, which is why treatment advances need to keep moving forward to provide the best options for all patients. 

Apart from those older or with chronic conditions, AML patients are currently treated with intensive chemotherapy regimens and stem cell transplants. However, most patients still need to switch treatments because the current one stops working, or the AML returns after a period of remission.

The Need for New AML Therapies 

Several therapies directed to specific mutations have been developed in the last decade. Within this category, LSD1 inhibitors constitute a promising option, and currently, several clinical trials are aiming to treat AML patients. 

What is Iadademstat? 

Iadademstat is an oral medication that works in two crucial sites of AML cells; inhibiting main enzyme activities of the lysine-specific demethylase 1 (LSD1; also known as KDM1A). It showed promising early activity and safety in a phase 1 trial and synergy with azacitidine in AML cells. 

What’s the Role of LSD1 in Blood Cells? 

LSD1 is a key regulator in the development and function of blood cells, playing an essential role in blood cell production. Even before we are born, LSD1 regulates important genes to control the transition of hematopoietic stem cells (HSCs) from their early stages to mature blood cells. 

LSD1 works at the epigenetic level (explained below) and helps suppress genes linked to the endothelial system that influences the AML environment in the bone marrow,  while it also stimulates the maturation of healthy bone marrow stem cells. It is critical not only for normal blood cell production but also for preventing the development of blood-related cancers like leukemia.

What is Epigenetic Therapy? 

Epigenetic therapy refers to treatments that target the genes that control modifications without changing the DNA sequence itself.  In AML, mutations in genes related to epigenetic regulation can disrupt normal gene expression, leading to the development and progression of the disease.

The ultimate goal of using epigenetic medications is to restore proper gene function. This opens the possibility of reprograming cancer cells to stop growing uncontrollably, promote their differentiation into normal cells, or induce cell death.

LSD1 inhibitors like iadademstat, which block a specific enzyme involved in histone modification, are an example of epigenetic therapy being explored for AML treatment. They offer a potential new way to target cancer at the molecular level.

Iadademstat News for AML Patients

Research efforts focus on delivering new options for relapsed and refractory AML patients and newly diagnosed AML patients who are starting therapy, resulting in specialized, tailor-made treatment strategies for all AML patients. 

Oryzon Genomics, S.A., an epigenetic-specialized biopharmaceutical company, announced that the first patient had been treated in a Phase Ib trial (NCT06357182) for newly diagnosed AML patients, testing iadademstat with venetoclax and azacitidine. 

Led by Dr. Curtis Lachowiez at the OHSU Knight Cancer Institute, this trial aims to assess the safety, tolerability, and optimal dose of this triple-drug regimen. 

• Venetoclax (Venclexta)  is a BCL-2 inhibitor, that potentiates the immune response to eliminate cancer cells.

• Azacitidine (Vidaza) is a chemotherapy drug, that decreases DNA methylation and alters gene expression regulating the activity of cancer cells.

This trial builds on previous results from Oryzon’s ALICE study in Spain, which showed that iadademstat combined with azacitidine had strong antileukemic effects and was well tolerated in patients. 

Oryzon is also conducting the FRIDA trial, which evaluates iadademstat with gilteritinib (Xospata) in relapsed or refractory AML with FLT3 mutations. This marks an important expansion for the clinical applications of iadademstat.

Conclusions

In conclusion, AML remains a challenging disease with limited long-term treatment success for many patients. Developing new therapies, like LSD1 inhibitors, offers hope for improved outcomes. Iadademstat is currently being studied in multiple clinical trials to assess its effectiveness in combination with other therapies. As research advances, these new treatments can potentially transform the care of AML patients.

If you want to track your labs and stay on top of your AML journey, you can create a free account and use all of HealthTree’s resources—the platform that powers life-saving research! 

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Clinical Trials for Iadademstat

Recruiting clinical trials with iadademstat

• Iadademstat in Combination With Azacitidine and Venetoclax in Treating Newly Diagnosed Acute Myeloid Leukemia patients 

• Study of Iadademstat and Gilteritinib in Patients With Relapsed/​Refractory AML patientsWith FMS-like Tyrosine Kinase Mutation (FLT3 Mut+) (FRIDA)

Not yet recruiting trial

•  Testing the Combination of an Anti-Cancer Drug, Iadademstat, With Other Anti-Cancer Drugs (Venetoclax and Azacitidine) for Treating AML

Sources: 

• What potential is there for LSD1 inhibitors to reach approval for AML?

• Lysine-Specific Demethylase 1A as a Promising Target in Acute Myeloid Leukemia

• ORYZON Announces First Patient Dosed in an Investigator-Initiated Phase Ib Study of Iadademstat in First-Line Acute Myeloid Leukemia

• Iadademstat in combination with azacitidine in patients with newly diagnosed acute myeloid leukaemia (ALICE): an open-label, phase 2a dose-finding study