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A dose determining trial to assess the recommended dose of ES-3000 and ASTX727 for patients with Myelodysplasia

Phase 1
Recruiting
Conditions
Myelodysplasia
Cancer - Leukaemia - Acute leukaemia
Registration Number
ACTRN12621001713886
Lead Sponsor
Australasian Leukaemia and Lymphoma Group
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
32
Inclusion Criteria

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.

Exclusion Criteria

Exclusion criteria 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.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
To assess the occurrence of dose limiting toxicities of ES-3000 to provide a recommended phase 2 dose. This will be completed by reviewing the patients blood biochemistry markers, peripheral blood counts for adverse events. [ After day 28 cycle 1 and cycle 2 have been completed for each dose cohort];To assess the incidence and severity of adverse events of ES-3000 and ASTX727. This will be completed by reviewing patients blood biochemistry markers, cell counts (peripheral blood and bone marrow) and physical exam. [ After all patients have completed day 28 cycle 2 ];To assess the overall response rates in the dose expansion phase of the trial.. This will be assessed using blood and bone marrow markers. [ After 3 and 6 months of treatment ]
Secondary Outcome Measures
NameTimeMethod
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