A study to evaluate the drug CC-486/oral azacitidine (Onureg) in patients with myeloid neoplasia and severe or moderate hepatic impairment

Myeloid neoplasms are disorders of the hematopoietic system in which the bone marrow produces defective blood cells or too many of them. These include myelodysplastic syndromes (MDS), in which immature blood cells do not mature properly, and myeloproliferative neoplasms (MPN), in which too many blood cells are produced. Some of these conditions, such as acute myeloid leukemia (AML), are aggressive forms of blood cancer, while others, such as chronic myelomonocytic leukemia (CMML), progress more slowly but can progress to more aggressive forms of leukemia. All of these diseases interfere with normal blood formation and can lead to anemia, susceptibility to infection, or a tendency to bleed.

Treatment for myeloid neoplasms depends on the type and severity of the disease. Chemotherapy is often used to destroy the cancer cells, particularly in aggressive forms such as AML. For slower-progressing diseases, such as MDS or MPN, targeted therapy or symptomatic treatment can help stabilize blood production. In some cases, a stem cell transplant may offer the possibility of a permanent cure. When treating patients, it is always important to take into account any other health limitations they may have. For example, liver dysfunction can limit the choice of medications. The liver metabolizes many drugs, and liver damage can cause a drug to be broken down more quickly or more slowly, resulting in a stronger or weaker effect. Depending on this, side effects may also increase.

The study drug Onureg (active ingredient: azacitidine) is taken in tablet form and is approved for maintenance therapy in adults with AML who are in remission following intensive chemotherapy but are unable to undergo a stem cell transplant. This can reduce the risk of relapse and prolong survival. Onureg (azacitidine) slows cancer growth by correcting faulty cellular processes and destroying cancer cells. Onureg is not yet approved for the other conditions identified in the study. In these cases, the active ingredient azacitidine is already approved when administered as a subcutaneous injection. Onureg is also not currently approved for use in patients with liver dysfunction, as dose adjustments may be necessary.

The goal of this study is to investigate the effects of moderate or severe liver dysfunction on the pharmacokinetics (absorption, distribution, metabolism, and excretion) of oral azacitidine (Onureg) and to evaluate its safety and tolerability. This should allow for better adjustment of the dosage and administration of Onureg in patients with impaired liver function.

Patients will be divided into 2 groups based on the severity of their liver dysfunction. One group will have severe liver impairment, and the other will have moderate liver impairment. A third group of patients with normal liver function will serve as the control group. To this end, the concentration of the active ingredient in the blood, as well as data on safety and efficacy, will be collected over a period of up to 9 months. All patients receive the study drug; the treatment is already approved for AML under certain conditions, but not for patients with liver dysfunction. The treatment is also experimental for the other types of myeloid neoplasms.

Women and men aged 18 and older who have various myeloid neoplasms are eligible to participate in the study. Patients must have moderate or severe impairment of liver function.