ClinTrial Refer

Trial Acronym
MYDAS-T Run ES IN

Registration Number
ACTRN12621001713886

Scientific Title
MDS05/D1: (MYDAS-T) Assessing the safety of ES-3000 and ASTX727 in patients with myelodysplasia

High risk MDS is a challenging condition with limited treatment options. Patients often depend on blood transfusions and unfortunately chemotherapy is rarely successful as a treatment option. The main type of therapy used in MDS are hypomethylating agents (HMAs) such as Azacitidine (AZA) and Decitabine (DEC). Traditionally, combination therapy has not proven to be effective in MDS given the increased toxicity of drugs used in combination with AZA, even where the overall responses may have been promising. Therefore, this trial aims to test a relatively non-cytotoxic drug called ES-3000, in combination with a HMA named ASTX727. 
Who is it for?
You may be eligible to join this study if you are aged 16 years or above, and have a diagnosis of MDS or acute myeloid leukaemia (AML) with <30% blasts.

Trial details:
All participants will receive treatment in 28-day cycles. At first, each participant will receive a single cycle of ES-3000 alone, in order to take blood samples at various timepoints throughout the day to establish how the drug is metabolised by the body. ES-3000 is an oral tablet administered three times per day on days 1-14 of the cycle. Each subsequent participant recruited to the trial will receive a higher dose of ES-3000, until the dose is no longer tolerated. From the second cycle onwards, participants will receive the same dose of ES-3000 in combination with a previously established safe dose of ASTX727 once per day on days 1-5 of each cycle. This will continue until the participant experiences either unacceptable toxicity, or disease progression. Participants will be monitored for adverse effects for the duration of treatment, as well as every 3 months for assessment of their response to treatment through blood samples and bone marrow biopsies, and assessment of quality of life through completion of a questionnaire.

It is hoped that this study may show that ES-3000 administered in combination with Inqovi is safe and effective for the treatment of MDS and AML. This study may help to inform the dosing of ES-3000 required for patients with these conditions in future.

Eligibility criteria are noted in the MDS05 Master Protocol as below:
1. Provision of written informed consent
2. Provision of written informed consent to the ALLG NBCR
3. Age 18+ (Age 16-17 permitted if consent for minor PICF approved by the authorising HREC)
4. A diagnosis of MDS or AML with < 30% blasts
5. Any other inclusion criteria mentioned in the study domain e.g., older AML patients (> 30% blasts) who are not suitable for intensive arms of AML trials or treatment may be suitable for certain domains of the MDS trials. This will be specified in the domain inclusion criteria.

The following point must also be met to be eligible for participation in this domain:
1. All previously treatment naïve myelodysplasia patients with IPSS score >= 1.5 and be eligible for standard AZA treatment in Australia. AML with blasts <30% (in peripheral blood and bone marrow) will also be eligible for this study.

as in the Master protocol will apply as below: 
1. History of other malignancy requiring active systemic treatment, or which is likely to result in an expected survival time of < 12 months.
2. Viral infection with known HIV or viral hepatitis type B or C not adequately controlled by antiviral medication.
3. 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, the following patients will be excluded:
1. Patients with QTcF> 480msecs (females) and QTcF> 450msecs (males) will be excluded from this study
2. Subjects who has received allogeneic HSCT or solid organ transplantation.
3. Subject has a history of an active malignancy within the past 2 years prior to study 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
4. Subject has a known positive test for human immunodeficiency virus (HIV). Note: HIV testing is not required at Screening.
5. Subject has chronic active hepatitis B (HBV) or hepatitis C (HCV) requiring treatment.
6. Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to ongoing systemic infection (viral, bacterial, or fungal).
7. Subject has a malabsorption syndrome or other condition that precludes an enteral route of administration.
8. Subject has 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 study or interpretation of study results. Note: For subjects who have required an intervention for any above diseases within the past 6 months requires a discussion between the investigator and study team.
9. Subject is concurrently participating in another therapeutic clinical trial.
10. Subject is pregnant or breastfeeding.

Trial Location Name

Address

Status

Calvary Mater Newcastle Hospital (Haematology)

Edith St & Platt St, Waratah NSW 2298, Australia

Recruiting

Primary Contact : Kath Hall, Kathy.Hall@calvarymater.org.au , 02 4014 4891

Australasian Leukaemia and Lymphoma Group

Website URL

Link Name

Link URL

ANZCTR

http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12621001713886

Secondary IDs
N/A

Study Type
Interventional

Intervention Code
Treatment - Drugs

Phase
Phase 1/Phase 2

Minimum Age
16

Maximum Age
100

Date Registered
17/06/2024

Date Closed
N/A

Status
Open

Enrolment Type
By Specialist and/or Surgeon Referral

Mutation Status and Biomarker
Any or not stated

Is it a Cohort Trial?
No

Is this a Tele-Trial?
No

Can healthy volunteer participate?
No

Discipline

Health Condition

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