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Trial registered on ANZCTR


Registration number
ACTRN12625000201471p
Ethics application status
Not yet submitted
Date submitted
5/02/2025
Date registered
20/02/2025
Date last updated
22/06/2025
Date data sharing statement initially provided
20/02/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
ALLG MDS05 (MYDAS-T)/D3 (MESSAGE): Myelodysplasia Advancing Strategies in Therapy platform trial - Mesenchymal signal targeting in Myelodysplasia as a pathway to transfusion independence and blood count improvement
Scientific title
ALLG MDS05 (MYDAS-T)/D3 (MESSAGE): Myelodysplasia Advancing Strategies in Therapy platform trial - Mesenchymal signal targeting in Myelodysplasia as a pathway to transfusion independence and blood count improvement
Secondary ID [1] 311981 0
None
Universal Trial Number (UTN)
Trial acronym
MDS05/D3
Linked study record
This is a component study associated with master protocol registered as ACTRN12622000410752

Health condition
Health condition(s) or problem(s) studied:
Myelodysplasia 333593 0
Condition category
Condition code
Cancer 330277 330277 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
There are two drugs used in this treatment domain of the MDS05 platform trial: PXS5505 and ASTX727 (35 mg Decitabine and 100mg Cedazuridine). This trial domain will be conducted in 2 parts;

Part 1: Phase Ib Safety and Dose-Determination
Patients will begin to receive trial treatment at starting dose level 0:
-oral PXS5505 (200 mg) twice a day from days 1 to 28
-oral ASTX727 (35mg decitabine and 100mg cedurazine) daily on days 1, 3 and 5 of cycle 1 (28-day cycle).
If a treatment-related toxicity arises, the Investigator will determine the grade of severity of the toxicity, causality (relationship to investigational agent), expectedness, and, if considered clinically appropriate, adjust the frequency according to levels below:
- Level 1: PXS5505 (200mg, twice a day, days 1-28), ASTX727 (daily, days 1-3)
- Level -1: PXS5505 (150mg, twice a day, days 1-28), ASTX727 (daily, days 1, 3 and 5)
- Level -2: PXS5505 (150mg, twice a day, days 1-28), ASTX727 (daily, days 1 and 3)

This phase will recruit up to 12 patients. Once the recommended phase 2 dose (RP2D) is determined, patients will proceed to phase 2.

Part 2: Phase II Dose-Expansion Safety
Patients will receive oral PXS5505 (200 or 150 mg) and ASTX727 (35mg decitabine and 100mg cedazuridine) at the RP2D dosage frequency determined in Part 1 of this trial.
This phase will recruit up to an additional 18 patients.

All treatment will be administered by the study team. Drug accountability will be performed by the administering institutions to assess compliance.
Intervention code [1] 328443 0
Treatment: Drugs
Comparator / control treatment
There is no comparator arm.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 338236 0
To determine efficiency of PXS-5505 with ASTX727 based on transfusion independence (TI).
Timepoint [1] 338236 0
Assessed at the end of cycle 4 and 6 of therapy
Primary outcome [2] 338235 0
The determine the safety and tolerability of PXS-5505 with ASTX727 when given in combination in patients with transfusion dependent Myelodysplastic Syndrome (MDS).
Timepoint [2] 338235 0
Assessed in cycle 1 as the events occur during this time.
Primary outcome [3] 338238 0
To determine efficiency of PXS-5505 with ASTX727 based on haematologic response (HR) rates.
Timepoint [3] 338238 0
Assessed at the end of cycle 4 and 6 of therapy
Secondary outcome [1] 435099 0
Event free survival (EFS). This will be assessed as a composite outcome
Timepoint [1] 435099 0
Response assessments at cycle 2 day 28 (C2D28), C3D1, C4D28, C5D1, C6D28, C7D1, at end of treatment and during post treatment follow-up visit.
Secondary outcome [2] 435100 0
Patient Reported Outcomes (PRO's). This will be assessed as a composite outcome
Timepoint [2] 435100 0
At screening, at Day 1 of every cycle of treatment and at post-treatment follow-up.

Eligibility
Key inclusion criteria
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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Eligible patients must not meet any of the exclusion criteria from the MDS05 Master Protocol listed below:
- History of other malignancy requiring active systemic treatment, or which is likely to result in an expected survival time of less than 12 months.
- Viral infection with known HIV or viral hepatitis type B or C not adequately controlled by antiviral medication
- Prior bone marrow or stem cell transplantation for a diagnosis of Myelodysplasia or acute myeloid leukaemia. If stem cell transplantation has been undertaken for other reasons- refer to individual domain and discuss with study team.

In addition, eligible patients must not meet these specific domain exclusion criteria:
2. MDS with suspected (based on personal and family history) or confirmed germline predisposition.
3. With del5q and WHO or ICC 2022 diagnostic category of MDS/Myeloproliferative Neoplasms (MPN).
4. With Myelodysplastic syndrome with excess blasts-2 (MDS -EB2) (and/or blasts over 10 percent)
5. Who have received allogeneic HSCT or solid organ transplantation.
6. Are considered a potential candidate for allogeneic HSCT at the treating institution.
7. Significant neutropenia defined as:
(a) Absolute Neutrophil Count less than 1.0 x 10^9/L persistently or G-CSF dependent) and/or
(b) Thrombocytopenia - Platelet less than 50x 10^9/L persistently or platelet transfusion dependent.
8. QT corrected for heart rate by Fridericia's cube root formula (QTcF) greater than 480msecs for females and QTcF greater than 450msecs for males.
9. Splenomegaly greater than or equal to 5cm beyond normal in any dimension, measured by physical or radiological examination where necessary.
10. History of surgery within 2 weeks prior to trial registration, or anticipated major surgery during the trial period. Minor surgery such as endoscopy or skin excisions are allowed but should be discussed with CI.
11. History of aneurysm.
12. Has a history of an active malignancy within the past 2 years prior to trial entry, with the exception of:
a) Adequately treated in situ carcinoma of the cervix uteri,
b) Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin,
c) Asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy.
13. Has malabsorption syndrome or other condition that precludes an enteral route of administration.
14. History of a significant cardiovascular, endocrine, hepatic, immunologic metabolic, neurologic, psychiatric, pulmonary, renal disease, or any other condition that in the opinion of the investigator would adversely affect his/her participation in this trial.
15. Participating in another therapeutic clinical trial.
16. Known allergy or hypersensitivity to PXS-5505 or ASTX727 (35mg decitabine and 100mg cedazuridine) or their compounds.
17. Life-expectancy is less than 12months.
18. Women who are pregnant or breastfeeding.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
24/09/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 316330 0
Other Collaborative groups
Name [1] 316330 0
Australasian Leukaemia and Lymphoma Group (ALLG)
Country [1] 316330 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group (ALLG)
Address
Country
Australia
Secondary sponsor category [1] 318511 0
None
Name [1] 318511 0
Address [1] 318511 0
Country [1] 318511 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 315139 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 315139 0
Ethics committee country [1] 315139 0
Australia
Date submitted for ethics approval [1] 315139 0
03/03/2025
Approval date [1] 315139 0
Ethics approval number [1] 315139 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133790 0
A/Prof Anoop Enjeti
Address 133790 0
Calvary Mater Newcastle Level 4, New Med Bldg, Edith Street Waratah NSW 2298
Country 133790 0
Australia
Phone 133790 0
+61 0240143021
Fax 133790 0
Email 133790 0
[email protected]
Contact person for public queries
Name 133791 0
Delaine Smith
Address 133791 0
ALLG, 35 Elizabeth St, Richmond, VIC 3121
Country 133791 0
Australia
Phone 133791 0
+61 3 8373 9701
Fax 133791 0
Email 133791 0
[email protected]
Contact person for scientific queries
Name 133792 0
Delaine Smith
Address 133792 0
ALLG, 35 Elizabeth St, Richmond, VIC 3121
Country 133792 0
Australia
Phone 133792 0
+61 3 8373 9701
Fax 133792 0
Email 133792 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Data are potentially available to:
• Researchers from not-for-profit organisations
• Commercial organisations
• Other
Based in:
• Any location
Further information:
All data requests will be considered by the primary sponsor on a case by case basis. Requests must include a methodologically sound proposal. Specific conditions of use may apply that the requester must agree to before access is granted.

Conditions for requesting access:
• -

What individual participant data might be shared?
• De-identified IPD data for all data collected during the trial

What types of analyses could be done with individual participant data?
• Any type of analysis
Assessed on a case-by-case basis

When can requests for individual participant data be made (start and end dates)?
From:
Data available 3 months following publication, for an indefinite period

To:
-

Where can requests to access individual participant data be made, or data be obtained directly?
• Access can be requested via the Health Data Australia catalogue (https://researchdata.edu.au/health/). Search for the ACTRN number in the catalogue to find datasets associated with this trial or email enquiries to [email protected]

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

TypeCitationLinkEmailOther DetailsAttachment
Study protocol  [email protected] Access can be requested via the Health Data Austra... [More Details]


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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