PREACH-M: This phase II trial is trying to understand whether treatment responses for people with Chronic Myelomonocytic Leukaemia can be improved by targeting certain gene mutations with certain cancer drugs (such as lenzilumab, azacitidine and sodium ascorbate)Precision Medicine for Chronic Myelomonocytic Leukaemia in Adults: A phase II Trial Studying the Efficacy of Lenzilumab and High Dose Ascorbate with Azacitidine Based on Molecular Profiling.

Exclusion

1. Prior hypomethylating or intensive cytotoxic treatment for CMML except for
hydroxyurea. Hydroxyurea may be given prior to starting active protocol treatment
and during the first 14 days of Cycle 1 only
2. Prior treatment with an investigational agent, or radiotherapy within 28 days before
Cycle 1 Day 1 (or within 5 half-lives of the investigational agent, whichever is longer).
Participants must have recovered from the toxic effects of that therapy to <= Grade 1 or
baseline grade.
3. Major surgery within 2 weeks or having not recovered from surgery.
4. Treatment with G-CSF within 7 days of screening or GM-CSF within 28 days of
screening.
5. Serious medical or psychiatric illness likely to interfere with participation in this clinical
study
6. Other concurrent uncontrolled medical conditions. These include, but are not limited
to: uncontrolled diabetes, uncontrolled infections, acute or chronic liver and renal
disease, uncontrolled cardiovascular conditions, including ongoing cardiac arrhythmias
(e.g. ventricular arrhythmias or Torsades de Pointes, or third-degree heart block without
pace maker insertion) or uncontrolled congestive cardiac failure.
7. Myocardial infarction or clinically significant pericardial effusion within the past month.
8. Another primary malignant disease that requires active treatment. Basal or squamous cell skin carcinomas adequately treated are allowed.
9. Acute or chronic liver disease (including chronic hepatitis B and C infections). Hepatitis B Virus core antibody positivity is not an automatic exclusion.
10. Patients with known active Hepatitis A infection. Testing for Hepatitis A is not required as part of screening for this study.
11. Participants with known human immunodeficiency viruses (HIV). Screening for HIV is not required for this study.
12. Participants who are unable to comply with requirements for contraception as per study requirements.
13. Prior allogeneic stem cell transplantation.
14. Current participation in another therapeutic clinical trial (participation in clinical trials that do not involve active interventions is not an exclusion for the study).