Study of Ziftomenib with Chemotherapy for Children with Relapsed or Refractory Acute Leukemia

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What is this study about?

This clinical trial is focused on studying treatments for children with certain types of acute leukemia, which is a cancer of the blood and bone marrow. The specific types of leukemia being studied include Acute Myeloid Leukemia, Mixed Phenotype Acute Leukemia, and Acute Lymphocytic Leukemia. The trial will test a new treatment called Ziftomenib, also known by its code name KO-539, in combination with standard chemotherapy drugs. Chemotherapy drugs used in this study include Cytarabine and Fludarabine phosphate, which are given through injections or infusions. The purpose of the study is to find the best dose of Ziftomenib when used with these chemotherapy drugs.

Participants in the study will receive Ziftomenib in the form of a hard capsule taken by mouth, along with chemotherapy. The study will also include a group receiving a placebo, which is a substance with no active medication. The trial aims to determine the safety and how the body processes Ziftomenib, as well as to observe any side effects. The study will monitor participants over a period of time to assess the effectiveness of the treatment and any potential improvements in their condition.

The trial is designed for children who have experienced a return of their leukemia or whose leukemia has not responded to previous treatments. The study will help researchers understand how well Ziftomenib works in combination with chemotherapy and will provide important information about its safety and potential benefits for treating these types of leukemia in children. The estimated completion date for the study is the end of 2028.

1 initial treatment phase

The treatment begins with the administration of ziftomenib in the form of hard capsules. This medication is taken orally.

In addition to ziftomenib, cytarabine and fludarabine phosphate are administered intravenously. These medications are part of the chemotherapy regimen.

2 combination therapy

The combination therapy involves the continued use of ziftomenib along with the chemotherapy drugs cytarabine and fludarabine phosphate.

The goal of this phase is to determine the recommended dose of ziftomenib when used with chemotherapy, focusing on safety and how the body processes the drug.

3 supportive care

During the trial, hydrocortisone may be administered intrathecally, which means it is injected into the spinal canal. This is done to manage inflammation and other symptoms.

Supportive care is provided to manage any side effects or adverse reactions that may occur during the treatment.

4 monitoring and assessment

Regular monitoring is conducted to assess the effectiveness of the treatment and to check for any dose-limiting toxicities.

Pharmacokinetic studies are performed to understand how ziftomenib is absorbed, distributed, metabolized, and excreted by the body.

5 follow-up

After completing the treatment cycles, follow-up assessments are conducted to evaluate the overall response to the therapy.

The follow-up includes checking for measurable residual disease and monitoring for any long-term effects of the treatment.

Who Can Join the Study?

Patients must be between 0-21 years old and weigh at least 5 kg. Most patients should be under 18 years old.
Female patients with infants must agree not to breastfeed during the study.
Patients who can have children must agree to use a very effective birth control method during the study and for 6 months after it ends. Male patients must use a condom and agree not to father a child or donate sperm during the study and for 6 months after it ends.
Patients must have recovered from the immediate side effects of any previous cancer treatments. This includes waiting a certain number of days after different types of treatments, such as:
- 21 days after treatments like interleukins or interferons.
- 14 days after long-acting growth factors or 7 days for short-acting ones.
- 14 days after local radiation therapy, 84 days after certain types of extensive radiation, or 42 days after other significant radiation.
- 84 days after a bone marrow or stem cell transplant, with some exceptions for mild conditions.
- 30 days after cellular therapies like modified T cells.
- Patients who had a different menin inhibitor can join unless they had severe side effects from it.
- 14 days after cytotoxic chemotherapy, except for certain medications like hydroxyurea or corticosteroids.
- No waiting period is needed for certain intrathecal therapies.
- 21 days after antibody-drug treatments, or after two half-lives for other antibody treatments.
Patients must have a specific type of leukemia that has returned or not responded to standard treatments.
Patients must meet certain conditions related to their leukemia, such as having a certain percentage of cancer cells in their bone marrow.
Patients in the US and Canada must have enrolled in a specific trial before joining this one.
Patients must have a certain level of physical ability, measured by a performance score.
Patients must have adequate organ function, including:
- Kidney function with a creatinine clearance of at least 60 mL/min.
- Liver function with specific levels of bilirubin and liver enzymes.
- Heart function with certain measures of heart performance and no signs of heart failure.
Written consent must be provided by the patient or their guardian, and assent from the child if applicable.
Female patients who can become pregnant must have a negative pregnancy test before joining the study.

Who Cannot Join the Study?

Patients who have a different type of leukemia than the ones being studied cannot participate. The study is focused on specific types of leukemia: Acute Myeloid Leukemia, Mixed Phenotype Acute Leukemia, and Acute Lymphocytic Leukemia.
Patients who do not have the specific genetic changes being studied cannot participate. These changes are called KMT2A-r, NUP98-r, or NPM1-m. These are specific genetic markers found in some leukemia cases.
Patients who are not within the age range specified for the study cannot participate. The study is for children, so adults are not eligible.
Patients who are not able to safely receive the study treatment due to other health conditions or risks cannot participate. This is to ensure the safety of all participants.
Patients who are unable to follow the study procedures or attend required visits cannot participate. This is important for collecting accurate data and ensuring participant safety.

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

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Other Sites

Site Name	City	Country
St. Anna Kinderspital GmbH	Vienna	Austria
Fondazione IRCCS San Gerardo Dei Tintori	Monza	Italy
Prinses Maxima Centrum voor Kinderoncologie B.V.	Utrecht	The Netherlands
Centre Hospitalier Universitaire De Nantes	Nantes	France
Hopital Beaujon	Clichy	France
Ospedale Pediatrico Bambino Gesu’	Rome	Italy
Hgiiuris Vsat dxhznvfv	Barcelona	Spain

Trial status

Country	Status	Recruitment Start
Austria	Recruiting	01.11.2024
France	Recruiting	01.11.2024
Italy	Recruiting	01.11.2024
Spain	Recruiting	01.11.2024
The Netherlands	Recruiting	01.11.2024

Trial locations

Investigated drugs:

Ziftomenib is a medication being studied for its potential to treat certain types of acute leukemia in children. It works by inhibiting a protein called menin, which is involved in the growth of cancer cells. The trial aims to find the best dose of ziftomenib when used with chemotherapy to ensure it is safe and effective for children whose leukemia has returned or is not responding to other treatments.

Chemotherapy (FLA) is a combination of cancer-fighting drugs used to kill or stop the growth of cancer cells. In this trial, chemotherapy is used alongside ziftomenib to enhance the treatment’s effectiveness against specific types of acute leukemia in children. The goal is to determine how well this combination works and to find the safest and most effective dose.

Acute Myeloid Leukemia – 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. Symptoms may include fatigue, fever, frequent infections, and easy bruising or bleeding. The disease can spread to other parts of the body, including the lymph nodes, liver, spleen, and central nervous system. It is more common in adults but can occur at any age. The progression is typically fast, requiring prompt medical attention.

Mixed Phenotype Acute Leukemia – A rare form of leukemia that exhibits features of both acute myeloid leukemia and acute lymphoblastic leukemia. It involves the presence of both myeloid and lymphoid cell markers in the same leukemia cells. This type of leukemia can be challenging to diagnose due to its mixed characteristics. Symptoms often include fatigue, fever, frequent infections, and bleeding or bruising easily. The disease can progress rapidly, affecting the bone marrow and other organs. It requires careful evaluation to determine the most appropriate treatment approach.

Acute Lymphocytic Leukemia – A cancer of the blood and bone marrow that affects white blood cells, specifically lymphocytes. It progresses quickly and is most common in children, though it can also occur in adults. Symptoms may include fatigue, fever, frequent infections, and easy bruising or bleeding. The disease can spread to other parts of the body, such as the lymph nodes, liver, spleen, and central nervous system. It is characterized by the overproduction of immature lymphocytes, which crowd out normal cells. The rapid progression necessitates immediate medical intervention.

Trial ID:

2023-505262-28-00

NCT ID:

NCT06376162

Trial Phase:

Human Pharmacology (Phase I) – Other

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