Recruiting

Study of Azacitidine, Venetoclax, and Tagraxofusp for Patients with Higher-Risk Chronic Myelomonocytic Leukemia

Fast replyRegistered drug

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

What is this trial about?

A plain-language summary of the goals, design and what participants do

This clinical trial is focused on studying a type of blood cancer called chronic myelomonocytic leukemia (CMML), which is considered higher-risk. The study will explore the effects of combining three treatments: azacitidine (AZA), venetoclax (VEN), and tagraxofusp (TAG). Azacitidine is a standard treatment for certain blood disorders, while venetoclax and tagraxofusp are additional medications being tested for their effectiveness in this combination.

The purpose of the study is to gather information on how well these treatments work together in patients with higher-risk CMML. Participants will receive these medications over a period of up to 12 months. The study will monitor the response to the treatment, including any changes in the disease and overall health. The medications will be given in different forms: venetoclax as a film-coated tablet taken by mouth, and tagraxofusp as a solution for infusion, which means it is administered directly into the bloodstream through a vein.

Throughout the study, participants will be closely observed for any side effects or changes in their condition. The study aims to understand the potential benefits and risks of this treatment combination, as well as its impact on the quality of life for those with higher-risk CMML. The results will help determine if this combination of treatments can be a viable option for managing this type of leukemia.

The research process

The trial runs in 5 steps – from screening to follow-up. Each step says what happens and what the team monitors.

Step 1
Initiation of treatment
The treatment begins with the administration of azacitidine (AZA), venetoclax (VEN), and tagraxofusp (TAG).
Azacitidine is given as part of the standard care for patients with higher-risk chronic myelomonocytic leukemia (CMML).
Step 2
Medication administration
Venetoclax is taken orally in the form of film-coated tablets.
Tagraxofusp is administered through an intravenous (IV) infusion as a solution for infusion.
Step 3
Treatment cycles
The treatment is organized into cycles. Each cycle includes the administration of the medications as described.
The primary outcome measure is assessed after 3 cycles of treatment, focusing on the response rate.
Step 4
Monitoring and assessment
Throughout the trial, regular monitoring of adverse events, clinical laboratory values, vital signs, and heart function is conducted.
The response to treatment is evaluated using specific criteria to determine the effectiveness of the therapy.
Step 5
Evaluation of outcomes
The primary outcome is the response rate after 3 cycles, defined as complete response (CR), marrow complete response (mCR), or partial response (PR).
Secondary outcomes include overall survival, time to leukemia transformation, and changes in quality of life after 3 and 12 cycles.

Who can join the trial?

14 criteria

Must sign a written informed consent form, which means you agree to participate in the study after understanding all the details.
Must be 18 years or older at the time of signing the informed consent.
Must be able to follow the study visit schedule and other study requirements.
Must have a diagnosis of chronic myelomonocytic leukemia (CMML) according to the World Health Organization (WHO) 2022 criteria.
Must have a CPSS risk of intermediate-2 or high for CMML at the start of the study. CPSS is a scoring system used to assess the risk level of CMML.
Must be eligible for and will receive azacitidine (AZA) as part of the standard treatment.
Must have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale, which measures how well you can perform daily activities.
check
Must have adequate organ function, including:
- Liver: Total bilirubin less than 1.5 times the upper limit of normal, and liver enzymes (ALT and AST) less than 2.5 times the upper limit of normal.
- Kidneys: Creatinine clearance of 45 mL/minute or higher, which measures how well your kidneys are working.
- Heart: Left ventricular ejection fraction (LVEF) of 50% or higher, which measures how well your heart pumps blood, and no significant abnormalities on an electrocardiogram (ECG).
- Albumin: Serum albumin level of 3.2 g/dL or higher, which is a protein in your blood.
- Must have available blood counts and transfusion records for the previous 8 weeks.
- Women who can have children must use a highly effective method of birth control during the study and for 6 months after the last dose. They must also have a negative pregnancy test before starting treatment and agree to regular pregnancy tests during the study.
- Men who are sexually active with women who can have children must use a highly effective method of birth control during the study and for 3 months after the last dose. They must also agree not to donate sperm during this time.

Who cannot join the trial?

4 criteria

Patients who have a different type of cancer than chronic myelomonocytic leukemia cannot participate. This is a specific type of blood cancer.
Patients who are not within the specified age range for the study cannot participate. The study is designed for certain age groups only.
Patients who are part of a vulnerable population, such as those who cannot make decisions for themselves, are not included in the study.
Patients who are not able to follow the study procedures or take the study medications as required cannot participate.

Clinical Trials Concierge

Prefer not to search? Our Concierge searches the trials for you.

Tell us about your condition – we search every trial in Europe and connect you with the right site.

We usually reply within a few days

Verified sites

All sites with verified contact details – recruitment status may not be available; ask directly

Verified
ASST Fatebenefratelli Sacco
Milan, Italy
Responsive
Azienda Ospedaliero Universitaria Careggi
Florence, Italy
Responsive
Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz
Madrid, Spain

Trial locations

Where you can join this trial

Countries are shaded by recruitment status. Click a recruiting country to ask about joining there.

Recruiting

Not finding your country?

Not sure what to do next?

Joining a clinical trial can seem overwhelming. We guide you step by step, so you know exactly what to expect and how we support you through the process.

See the full process and FAQ

Investigated drugs

Azacitidine
is a medication used to treat certain types of blood disorders. It works by helping to restore normal growth of blood cells and reducing the number of abnormal blood cells. In this trial, it is part of the standard care therapy for patients with higher-risk chronic myelomonocytic leukemia.
Venetoclax
is a medication that helps to kill cancer cells by blocking a protein that helps them survive. It is used in combination with other treatments to improve their effectiveness in treating certain types of leukemia.
Tagraxofusp
is a medication that targets specific cancer cells and helps to destroy them. It is used in this trial to see if it can improve outcomes for patients with higher-risk chronic myelomonocytic leukemia when combined with other treatments.

What is already known about the treatment

Azacitidine
Azacitidine is administered as an injection under the skin or into a vein. It is currently used in medical practice and literature for treating certain blood disorders, including chronic myelomonocytic leukemia. The main therapeutic indication is to help restore normal growth of bone marrow cells and reduce the number of abnormal blood cells. At the molecular level, azacitidine works by incorporating into RNA and DNA, inhibiting the growth of cancer cells. It is classified as a nucleoside metabolic inhibitor.
Venetoclax
Venetoclax is taken orally in the form of tablets. It is recognized in medical literature for its role in treating certain types of leukemia, including chronic myelomonocytic leukemia. The primary therapeutic use is to help induce cancer cell death. Venetoclax works by inhibiting a protein called BCL-2, which helps cancer cells survive. It is classified as a BCL-2 inhibitor.
Tagraxofusp
Tagraxofusp is administered through an intravenous infusion. It is currently being studied for its effectiveness in treating chronic myelomonocytic leukemia. The main therapeutic indication is to target and kill cancer cells. At the molecular level, tagraxofusp is a fusion protein that binds to the interleukin-3 receptor on cancer cells, delivering a toxin that leads to cell death. It is classified as a CD123-directed cytotoxin.

Investigated diseases

Chronic Myelomonocytic Leukemia – This is a type of cancer that affects the blood and bone marrow, characterized by an increase in monocytes, a type of white blood cell. It typically progresses slowly, with symptoms that may include fatigue, fever, and weight loss. Over time, the disease can lead to anemia, increased risk of infections, and bleeding issues due to low blood cell counts. The bone marrow, which is responsible for producing blood cells, becomes dysfunctional, leading to an imbalance in blood cell production. As the disease advances, it may transform into acute myeloid leukemia, a more aggressive form of blood cancer. The progression and symptoms can vary significantly among individuals.