Combining Azacitidine and Venetoclax for Higher-Risk Chronic Myelomonocytic Leukemia

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    What is this study about?

    The AVENHIR study is an open-label clinical trial for patients with higher-risk chronic myelomonocytic leukemia, a type of blood cancer. This study will evaluate the effectiveness and safety of combining two drugs: Azacitidine and Venetoclax (also known as ABT-199). Azacitidine is a chemotherapy drug, while Venetoclax is a targeted therapy that works by blocking a specific protein in cancer cells.

    The main goals of the study are to determine the overall response rate to this drug combination, which means how many patients achieve complete remission, partial remission, or clinical benefit. The study will also closely monitor safety and any potential dose-limiting side effects during the first two treatment cycles.

    To be eligible for this study, patients must be newly diagnosed with higher-risk chronic myelomonocytic leukemia and have not received any prior treatment with hypomethylating agents like Azacitidine.

    Learn more about this Trial

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      Locations

      Where does the clinical trial take place?

      Amiens , France

      Angers , France

      Bobigny , France

      Grenoble , France

      Limoges , France

      Marseille , France

      Montpellier , France

      Nantes , France

      Nantes , France

      Nice , France

      Paris , France

      Paris , France

      Pierre-Bu00e9nite , France

      Poitiers , France

      Rennes , France

      Rouen , France

      Toulouse , France

      Tours , France

      Villejuif , France

      You can join this study in:

      Study Steps

      How Complex Will My Study Be and What Phases Will I Go Through?

      Here are the key steps a patient would go through in this clinical trial of azacitidine combined with venetoclax for higher-risk chronic myelomonocytic leukemia (CMML):

      1. Patients receive azacitidine subcutaneously at a dose of 75 mg/m2 per day, either on days 1-7 or using a 5-2-2 schedule, of each 28-day treatment cycle.
      2. Patients also take venetoclax orally during the first 7 or 14 days of each 28-day cycle (exact number of days determined during safety run-in phase of trial):
        • Cycle 1: Venetoclax given with 3-day ramp-up – 100 mg on day 1, 200 mg on day 2, and 400 mg on days 3 to 7 (or 14)
        • Subsequent cycles: Venetoclax given at 400 mg on days 1 to 7 (or 14)
      3. Total treatment duration is 24 months (about 26 cycles).
      4. Patients are followed for response after 3 cycles and 6 cycles.
      5. Long-term follow-up continues for an average of 5 years to track outcomes like progression to acute myeloid leukemia, overall survival, etc.

      In summary, the trial involves receiving injections of azacitidine and taking oral venetoclax in 28-day cycles, for a total treatment period of 24 months. Initial response is checked at 3 and 6 cycles, with longer-term monitoring for an average of 5 years. The exact timeline depends on the individual patient’s course in the study.


      Diseases Under Investigation

      What Conditions Qualify Me for This Study?

      Chronic myelomonocytic leukemia (CMML) is a type of cancer that affects the blood and bone marrow, which is the soft, spongy center of the bones where blood cells are made. In CMML, the body produces too many monocytes, a type of white blood cell. This disease can vary widely in its severity and how fast it progresses, depending on the characteristics of the cancer cells present. CMML is considered a type of leukemia known as myelodysplastic/myeloproliferative disease, which features aspects of both the overproduction and the ineffective production of cells.


      Terms and conditions

      What Requirements I Have to Meet To Join This Study?

      When Am I Eligible to Join the Study?

      Here are the eligibility criteria for the study on chronic myelomonocytic leukemia (CMML):

      1. Age Requirement: Participants must be 18 years or older.
      2. Diagnostic Criteria: Must have a confirmed diagnosis of CMML according to the World Health Organization (WHO) 2016 criteria.
      3. Disease Risk: Must be classified as intermediate-2 or high risk according to the CMML Prognostic Scoring System (CPSS).
      4. Treatment History: Cannot have prior treatment with hypomethylating agents. Limited prior treatment with hydroxyurea or erythropoiesis-stimulating agents is allowed under specific conditions.
      5. Performance Status: Must have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) Scale.
      6. Organ Function: Must have adequate liver, kidney, and bilirubin levels.
      7. Consent: Must be able to sign the Informed Consent Form.
      8. Reproductive Status: Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception. Men must also agree to use contraception.

      What Reasons Could Exclude Me from the Study?

      Based on the eligibility criteria, you cannot take part in the AVENHIR study if you have any of the following:

      1. Other myeloproliferative or myelodysplastic disorders besides CMML: The study is specifically for patients with chronic myelomonocytic leukemia (CMML) and not other similar blood disorders.
      2. Bone marrow or blood blasts 20% or higher: Blasts are immature blood cells. If the percentage of blasts in your bone marrow or blood is too high, you are not eligible.
      3. CMML with certain genetic changes (t(5;12) or PDGFRbeta rearrangement): These specific genetic abnormalities disqualify you because they indicate your CMML may respond to a different treatment (imatinib).
      4. Low or intermediate-1 risk score: Your CMML must be intermediate-2 or high risk based on the CMML Prognostic Scoring System. Lower risk scores make you ineligible.
      5. Pregnant or breastfeeding: The study drugs may harm a fetus or nursing baby.
      6. Serious coexisting medical conditions: Certain active infections, autoimmune disorders requiring high steroid doses, or other major illnesses could make study participation unsafe.
      7. Medications that strongly affect liver enzymes: You cannot be on drugs that significantly induce or inhibit CYP3A enzymes in the liver, as they could dangerously alter venetoclax levels.
      8. Certain prior cancers: Most other active cancers or cancers treated within the past 2 years are disqualifying, with a few exceptions like skin cancer.
      9. HIV positive: Known HIV infection excludes you from the trial.
      10. Severely reduced intestinal absorption: You must be able to take the study drugs orally.
      11. Prior hypomethylating agent treatment: If you previously received azacitidine, decitabine or similar drugs for any condition, you are ineligible.
      12. Prior venetoclax or similar drugs (BCL-2 inhibitors): Previous treatment with these targeted agents disqualifies you.
      13. Prior allogeneic stem cell transplant: You cannot have had a donor stem cell transplant already, but may be eligible for future transplant.

      Investigational Medicinal Product

      What Products Are Being Used in This Study?

      The following drugs are involved in the AVENHIR study:

      1. Azacitidine: This is a hypomethylating agent that is administered subcutaneously. It will be given at a standard dose of 75 mg/m2/d either on days 1-7 or using a 5-2-2 schedule of 28 day cycles. Azacitidine is being used in combination with venetoclax.
      2. Venetoclax (ABT-199): An oral medication that targets the BCL-2 protein. Patients will be exposed to venetoclax during the first 7 or 14 days of each 28 day cycle. The number of days of venetoclax treatment will be determined during the safety run-in phase. Venetoclax will be initially given with a 3-day ramp-up in cycle 1 (100 mg day 1, 200 mg day 2, 400 mg days 3-7 or 14). In subsequent cycles, it will be given at 400 mg on days 1-7 or 1-14 of each cycle. Venetoclax is being combined with azacitidine to evaluate efficacy and safety.

      Have the Medicinal Substances Used in the Trial Been Previously Studied in Medicine?

      1. Azacitidine: azacitidine is already a well-known drug in medicine and the medical literature. It is a chemotherapy medication used to treat myelodysplastic syndromes and acute myeloid leukemia.
      2. Venetoclax: venetoclax is also an established cancer treatment. It is a targeted therapy that inhibits the BCL-2 protein and is approved to treat chronic lymphocytic leukemia and acute myeloid leukemia.

      Study ID

      CT-EU-00116271

      Recruitment status

      Recruting new patients

      Start of the trial

      9 months ago

      Study phase

      Phase
      II

      Medicinal Product