Study on the Safety and Effectiveness of Ivosidenib or Enasidenib with Azacitidine for Patients with Newly Diagnosed Acute Myeloid Leukemia with IDH1 or IDH2 Mutations

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What is this study about?

This clinical trial is focused on studying treatments for Acute Myeloid Leukemia (AML), a type of cancer that affects the blood and bone marrow. The study involves patients who have a specific genetic change, known as a mutation, in enzymes called isocitrate dehydrogenase 1 or 2 (IDH1 or IDH2). These patients are not suitable candidates for intensive chemotherapy, which is a common treatment for cancer. The trial is testing two different combinations of medications: one combination includes oral tablets of Ivosidenib (also known as AG-120) with injections of Azacitidine, and the other combination includes oral tablets of Enasidenib Mesilate (also known as AG-221) with Azacitidine injections.

The purpose of the study is to evaluate the safety and effectiveness of these medication combinations in treating patients with newly diagnosed AML who have the IDH1 or IDH2 mutation. The study is divided into different stages. Initially, it will focus on finding the best dose of the medication combinations and assessing their safety. Later, the study will compare the effectiveness of the Enasidenib Mesilate and Azacitidine combination against Azacitidine alone in patients with the IDH2 mutation. Throughout the study, participants will receive either the medication combination or a placebo, and their health will be monitored to gather information on how well the treatments work and any side effects they may experience.

Participants in the trial will take part in regular visits to the study site, where they will receive their assigned treatment and undergo various health assessments. These assessments will help researchers understand how the treatments affect the body and how the disease responds to the medication. The study aims to provide valuable insights into new treatment options for patients with AML who have specific genetic mutations, potentially leading to improved outcomes for those affected by this challenging condition.

1 initial treatment phase

The trial begins with the administration of medications designed to target specific mutations in the leukemia cells. These medications include enasidenib mesilate and ivosidenib, both taken orally in the form of film-coated tablets.

The dosage for enasidenib mesilate is either 50 mg or 100 mg, depending on the specific requirements of the treatment plan. Ivosidenib is administered at a dosage of 250 mg.

In addition to the oral medications, azacitidine is given as a subcutaneous injection. This medication is provided as a 25 mg/ml powder for suspension for injection.

2 combination treatment phase

During this phase, the combination of oral medications and subcutaneous injections continues. The goal is to assess the safety and tolerability of these combinations in treating acute myeloid leukemia (AML) with specific genetic mutations.

The treatment involves either AG-120 (oral) with azacitidine (subcutaneous) or AG-221 (oral) with azacitidine (subcutaneous), depending on the mutation type (IDH1 or IDH2).

3 dose finding and expansion stage

This stage focuses on determining the recommended combination dose of the medications. The process involves monitoring for any dose-limiting toxicities and evaluating the overall safety and effectiveness of the treatment.

The expansion stage specifically assesses the combination of AG-120 with azacitidine in patients with an IDH1 mutation.

4 randomized treatment stage

In this stage, the effectiveness of AG-221 with azacitidine is compared to azacitidine alone in patients with an IDH2 mutation.

The objective is to evaluate the efficacy of the combination treatment in improving patient outcomes.

5 monitoring and follow-up

Throughout the trial, regular monitoring is conducted to assess the patient’s response to the treatment and to identify any side effects.

Follow-up visits are scheduled to ensure the continued safety and effectiveness of the treatment regimen.

Who Can Join the Study?

The person must be at least 18 years old when they sign the consent form.
The person must understand and willingly sign a consent form before any study-related activities begin.
The person must be willing and able to follow the study visit schedule and other study requirements.
The person must have newly diagnosed Acute Myeloid Leukemia (AML) with at least 20% cancerous cells in the bone marrow. They must have a specific gene mutation called IDH1 or IDH2 and should not be suitable for intensive chemotherapy.
The person must have a performance status of 0, 1, or 2, which is a way to measure how well they can perform daily activities.
The person must have proper organ function, which means:
- Certain liver enzymes (AST/SGOT and ALT/SGPT) should be no more than 3 times the normal limit, unless it’s due to leukemia affecting the organs.
- Total bilirubin, a substance in the blood, should be less than 1.5 times the normal limit, unless higher levels are due to specific conditions like Gilbert’s syndrome or leukemia affecting the organs.
- Creatinine, a waste product in the blood, should be less than 2 times the normal limit, or the kidneys should be able to filter at least 30 mL/min.
The person must agree to have repeated bone marrow tests.
Women who can have children must:
- Agree to avoid pregnancy by using effective birth control methods or abstaining from sex during the study and for at least 4 months after the last treatment.
- Have a negative pregnancy test before starting the study and within 72 hours before beginning treatment.
Men must:
- Agree to avoid fathering a child by using effective birth control methods or abstaining from sex during the study and for at least 4 months after the last treatment (6 months in Canada).
- Use a condom while being treated with azacitidine and for at least 4 months after the last dose.

Who Cannot Join the Study?

Patients who have a different type of cancer other than Acute Myeloid Leukemia (AML) cannot participate. AML is a type of blood cancer.
Patients who do not have a specific genetic change called an IDH1 or IDH2 mutation are excluded. These mutations are changes in the genes that can affect how cells grow.
Patients who are able to receive a strong form of treatment called intensive IC (intensive chemotherapy) are not eligible. Intensive IC is a powerful treatment that uses drugs to kill cancer cells.
Patients who are under the age of 18 or over the age of 75 are not eligible to participate.
Both male and female patients can participate, but they must meet all other criteria.
Patients who are considered part of a vulnerable population, such as those who cannot make decisions for themselves, are not eligible.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
Institut Gustave Roussy	Villejuif	France
Oncopole Claudius Regaud	Toulouse	France
Medizinische Hochschule Hannover	Hanover	Germany

Other Sites

Site Name	City	Country
Azienda Sanitaria Territoriale Di Pesaro E Urbino	Pesaro	Italy
Azienda Ospedaliero-Universitaria San Luigi Gonzaga	Orbassano	Italy
Institut fuer Klinische Transfusionsmedizin und Immungenetik Ulm gGmbH	Ulm	Germany
Aexevktqr Uio	Amsterdam	The Netherlands

Trial status

Country	Status	Recruitment Start
France	Not recruiting	18.06.2016
Germany	Not recruiting	18.06.2016
Italy	Not recruiting	18.06.2016
The Netherlands	Not recruiting	18.06.2016

Trial locations

Investigated drugs:

AG-120 is an oral medication being studied for its potential to treat acute myeloid leukemia (AML) in patients with a specific genetic mutation known as IDH1. This medication is designed to target and inhibit the abnormal enzyme activity caused by the IDH1 mutation, which may help slow down or stop the growth of cancer cells. In this trial, AG-120 is combined with another medication to evaluate its safety and effectiveness.

AG-221 is another oral medication included in the study, aimed at treating AML in patients with a different genetic mutation called IDH2. Similar to AG-120, AG-221 works by targeting the abnormal enzyme activity resulting from the IDH2 mutation. The goal is to determine if this medication can effectively manage the disease when used in combination with another treatment.

Azacitidine is a medication administered subcutaneously, meaning it is injected under the skin. It is used in this trial as part of a combination therapy with either AG-120 or AG-221. Azacitidine works by interfering with the growth of cancer cells, and it is commonly used to treat certain types of blood cancers. In this study, it is being evaluated for its potential to enhance the effects of the other medications in patients with AML.

Investigated diseases:

Acute myeloid leukaemia

Acute Myeloid Leukemia (AML) – Acute Myeloid Leukemia is a type of cancer that starts in the blood-forming cells of the bone marrow and quickly progresses to affect the blood. It is characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML can lead to symptoms such as fatigue, frequent infections, and easy bruising or bleeding due to the lack of healthy blood cells. The disease can progress rapidly, requiring prompt medical attention. It is often associated with genetic mutations, such as IDH1 or IDH2, which can influence the behavior of the leukemia cells. AML is considered a rare disease and can vary significantly in its presentation and progression among different individuals.

Trial ID:

2024-511722-31-00

Protocol code:

AG-221-AML-005

NCT ID:

NCT02677922

Trial Phase:

Human Pharmacology (Phase I) – Other

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Study on the Safety and Effectiveness of Ivosidenib or Enasidenib with Azacitidine for Patients with Newly Diagnosed Acute Myeloid Leukemia with IDH1 or IDH2 Mutations

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?