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.

ACTRN 12621000223831

Brief Summary

This study is investigating the efficacy of assigning targeted therapymedication that targets specific molecular features of cancer cells to Chronic Myelomonocytic Leukaemia (CMML) patients based on their individual molecular profile.

Intervention/Treatment

• Drug: Azacitidine.
• Drug: Lenzilumab.
• Drug: Sodium Ascorbate.

Inclusion Criteria

1. Confirmed diagnosis of CMML, including t-CMML, satisfying the WHO 2016 criteria.
2. Aged 18 or older.
3. Cytopenialow levels of red blood cells, white blood cells or platelets in the blood; one or more blood cell type can be affected, constitutional symptoms or proliferative CMML (white blood cell count >=13×10^9/L).
4. Detection of TET2 mutation or NRAS/KRAS/CBL mutation at a variant allele frequency of >=3%. Participants who are found to have both TET2 and RAS pathway mutations will be allocated to the lenzilumab/azacitidine arm of the study.
5. Eastern Cooperative Oncology Group (ECOG) performance status of <=2.
6. Based on known non-CMML related medical history, expected to have a life expectancy of >= 24 months.
7. Must have the following local laboratory results:
   • Liver function (total bilirubin <=1.5* x upper limit of normal [ULN], aspartate aminotransferase [AST] and alanine aminotransferase [ALT] <=3 x ULN). For participants with hepatomegalyenlargement of the liver due to extramedullary haematopoiesis, AST and/or ALT must be < 5 x ULN. *For participants with total bilirubin >1.5 x ULN, direct bilirubin must be <= ULN.
   • Kidney function: creatinine clearance >30 mL/min using Cockcroft-Gault formula. Note: the Adjusted Body Weight formula should be used for participants with a BMI of = 30.
     Actual Body weight should be used when BMI is < 30.
8. Ability to understand the requirements of the study and informed consent.
9. Reproductive status:
   • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
   • Women must not be breastfeeding.
   • WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug, plus 30 days (duration of ovulatory cycle) for a total of 30 days post-treatment completion.
   • Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 90 days (duration of sperm turnover) for a total of 90 days post-treatment completion.