MESSAGE: Testing how safe and manageable a new combination treatment is, and whether it can help people with myelodysplastic syndromes improve their blood counts and need fewer blood transfusionsMyelodysplasia Advancing Strategies in Therapy platform trial - Mesenchymal signal targeting in Myelodysplasia as a pathway to transfusion independence and blood count improvement

Inclusion

1. All of the inclusion criteria from the MDS05 Master Protocol listed below must be met:
- Provision of written informed consent
- Provision of written informed consent to the Australasian Leukaemia and Lymphoma Group (ALLG) National Blood Cancer Registry (NBCR).
- Age 18 or above (Age 16-17 permitted if consent for minor PICF approved by the authorising HREC)
- A diagnosis of MDS or Acute Myeloid Leukaemia (AML) with less than 30percent blasts

In addition, eligible patients must meet these specific domain inclusion criteria:
2. Co-enrolment to the ALLG NBCR.
3. Previously treatment naïve MDS patients with Revised International Prognostic Scoring System (IPSS-R) of very low, low or intermediate-1 (less than or equal to 4.5), and Molecular IPSS (IPSS-M) of less than 0.0 will be allowed if there are no other accompanying high-risk features) and are treatment naïve (apart from transfusions and standard supportive care).
4. Eastern Cooperative Oncology Group (ECOG) score 0-2.
5. Haemoglobin (Hb) less than 100 grams per Litre during the screening period and at baseline. Note: this should be rechecked prior to registration. Since Hb level estimation may vary between different laboratories due to difference in method/device, investigators should assess baseline Hb level (unless different laboratories have been shown to yield similar results).
a. For the determination of the baseline Hb level:
i. Hb measurements should be performed (or retrospective results should be available) on 3 separate occasions during the 16-weeks preceding the screening period.
ii. Use the mean of all available Hb measurements during the 16-week time frame to avoid bias, measurements prior to transfusions should be used in this calculation for transfusion dependent patients and a minimum of 2 measurements should be at least 7 days apart.
6. Red cell transfusion dependent (in absence of surgical procedure, bleeding, haemolysis or nutritional deficiency) defined as transfusion of at least 3 units of red blood cells (RBC), in atleast two transfusion episodes in the 16 weeks preceding the screening period.
a. Haemoglobin (Hb) levels at the time of or within 7 days prior to administration of a red blood cell transfusion must have been less than or equal to 100 grams per Litre in order for the transfusion to be counted towards meeting eligibility criteria. Note: Red blood cell transfusions administered when Hb levels were greater than 100 grams per Litre and-or RBC transfusions administered for elective surgery, infections or bleeding events will not qualify as a required transfusion for the purpose of meeting eligibility criteria.
b. Transfusion threshold should be pre-defined for individual patient and maintained throughout the trial, to minimise variation in threshold between pre-trial and on-trial practice of 100 grams per Litre. Exceptional circumstances must be discussed with the Chief Investigator and documented in the eCRF.
7. Women of childbearing potential (WOCBP) must be permanently sterile or agree to at least two forms of adequate contraception when sexually active excluding abstinence. Males that are sexually active with WOCBP must be permanently sterile or agree to adequate contraception. This applies for the time of consent until to 6 months after end of treatment.