Not recruitingRare disease

Study on the Safety and Effectiveness of Azacitidine and Venetoclax for Patients with Higher-Risk Chronic Myelomonocytic Leukemia (CMML)

Verified siteRegistered drugNo placebo

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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 blood cancer called Chronic Myelomonocytic Leukemia (CMML), specifically in patients who are at a higher risk. The study is investigating the safety and effectiveness of a combination treatment using two medications: Venetoclax and Vidaza (Azacitidine). Venetoclax is taken as a tablet, while Vidaza is given as an injection. The purpose of the study is to determine how safe this combination is for patients and how well it works in treating the disease.

Participants in the study will receive the combination of Venetoclax and Vidaza over a period of time. The study is divided into different phases, starting with a safety run-in phase to monitor any side effects. Following this, the main phase of the study will assess how the treatment affects the disease, including the overall response rate, which measures how the disease responds to the treatment. The study will also look at other outcomes, such as how long the response lasts and the overall survival of the participants.

The trial aims to provide valuable information about the potential benefits and risks of using Venetoclax and Vidaza together for treating higher-risk CMML. This information could help improve treatment options for patients with this type of leukemia. Participants will be closely monitored throughout the study to ensure their safety and to gather data on the effectiveness of the treatment.

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
Upon joining the study, the treatment begins with the administration of azacitidine and venetoclax.
Azacitidine is provided as a suspension for injection and is administered subcutaneously. The dosage and frequency are determined by the study protocol.
Venetoclax is taken orally in the form of film-coated tablets. The dosage and frequency are also specified in the study protocol.
Step 2
Safety run-in phase
The initial phase of the study focuses on assessing the safety of the combination of azacitidine and venetoclax.
This phase involves monitoring for any dose-limiting toxicities that may occur within the first two cycles of treatment.
Step 3
Phase II treatment
Following the safety run-in phase, the study progresses to the phase II portion.
The primary goal is to evaluate the overall response rate after 3 and 6 cycles of treatment. This includes assessing complete remission, partial remission, marrow response, and clinical benefit.
Step 4
Response evaluation
Throughout the study, the response to treatment is evaluated using specific criteria.
The criteria include modified guidelines for assessing response in myelodysplastic syndromes and myeloproliferative neoplasms.
Step 5
Monitoring and follow-up
Regular monitoring is conducted to assess the safety profile of the treatment, including both hematological and non-hematological effects.
Additional endpoints such as overall survival, progression-free survival, and event-free survival are also evaluated.

Who can join the trial?

11 criteria

Must be **18 years or older**.
Must have a **CMML diagnosis** according to the WHO 2016 criteria. CMML stands for Chronic Myelomonocytic Leukemia, a type of blood cancer.
Must be at **intermediate-2 or high risk** according to the CMML Prognostic Scoring System (CPSS). This system helps determine the severity of the condition.
Must not have had any prior treatment with **HMAs**. HMAs are a type of medication used to treat certain blood disorders. However, prior treatment with **Erythropoiesis Stimulating Agents (ESA)** is allowed if there has been a break of more than 15 days from these agents. Also, prior treatment with **hydroxurea (HY)** for less than 6 weeks is acceptable.
Must have an **ECOG Performance status** of 0-2. This is a scale used to assess how a disease affects a patient's daily living abilities, with 0 being fully active and 2 being able to do some activities but unable to work.
Must have **adequate organ function**:
- Total bilirubin less than 2 times the upper limit of normal (ULN). Bilirubin is a substance made by the liver.
- ALT and AST less than 3 times ULN. These are enzymes that help measure liver function.
- Creatinine clearance greater than 30 mL/min. This measures how well the kidneys are working.
- Must have signed an **Informed Consent Form**, which means agreeing to participate in the study after understanding all the details.
- If relevant, must have a **negative pregnancy test** and use adequate contraception. This applies to both male and female participants to prevent pregnancy during the study.
- Must be **affiliated with a health insurance system**.

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Verified sites

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

CHU Grenoble Alpes
Verified
La Tronche, France
Centre Henri Becquerel
Verified
Rouen, France
Centre Hospitalier Et Universitaire De Limoges
Verified
Limoges, France

Trial locations

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Investigated drugs

Azacitidine
is a medication used to treat certain types of blood disorders. In this trial, it is being used to help manage higher-risk Chronic Myelomonocytic Leukemia (CMML). Azacitidine works by interfering with the growth of cancer cells, which can help slow down the progression of the disease.
Venetoclax
is a medication that targets and blocks a specific protein in cancer cells, which can lead to the death of these cells. In this trial, venetoclax is combined with azacitidine to evaluate its safety and effectiveness in treating patients with higher-risk CMML. The combination aims to improve the overall response to treatment.

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 higher-risk chronic myelomonocytic leukemia (CMML). 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 DNA and RNA, leading to the inhibition of DNA methylation and RNA synthesis, which can reactivate tumor suppressor genes. It is classified as a hypomethylating agent.
Venetoclax
Venetoclax is taken orally in the form of tablets. It is recognized in medical literature as a treatment for certain types of leukemia, including higher-risk chronic myelomonocytic leukemia (CMML). The primary therapeutic use is to induce cancer cell death by targeting and inhibiting the BCL-2 protein, which helps cancer cells survive. At the molecular level, venetoclax binds to the BCL-2 protein, blocking its function and triggering apoptosis, or programmed cell death, in cancer cells. It is classified as a BCL-2 inhibitor.

Investigated diseases

Chronic Myelomonocytic Leukemia (CMML) – Chronic Myelomonocytic Leukemia is a type of cancer that starts in blood-forming cells of the bone marrow and invades the blood. It is characterized by an increase in monocytes, a type of white blood cell, in the blood. CMML is considered a type of myelodysplastic/myeloproliferative disease, which means it has features of both myelodysplastic syndromes and myeloproliferative neoplasms. The disease progresses as the abnormal cells accumulate in the bone marrow, leading to a decrease in the production of normal blood cells. Over time, this can result in symptoms such as fatigue, anemia, and increased risk of infections. In some cases, CMML can transform into acute myeloid leukemia, a more aggressive form of leukemia.