RecruitingPhase 2ACTRN12621001713886

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

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

Sponsor

Australasian Leukaemia and Lymphoma Group

Enrollment

32 participants

Start Date

Jun 30, 2023

Study Type

Interventional

Conditions

Myelodysplasia

Summary

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

Sex: Both males and femalesMin Age: 16 Yearss

Plain Language Summary

Simplified for easier understanding

Myelodysplasia (MDS) is a bone marrow disorder where the bone marrow doesn't produce healthy blood cells properly, often making patients dependent on blood transfusions. Standard treatments (called hypomethylating agents or HMAs) help some patients but don't work well for others. This study tests a new drug called ES-3000 in combination with an existing HMA called ASTX727 (also known as Inqovi) to find the safest and most effective dose of ES-3000. All participants will first receive one cycle of ES-3000 alone so researchers can study how the drug is processed by the body. From the second cycle onward, ES-3000 is combined with ASTX727. Starting doses are low and gradually increased in successive participants. Blood tests, bone marrow biopsies, and quality-of-life questionnaires will be collected throughout. You may be eligible if you are 16 years or older and have been diagnosed with MDS or a related blood cancer called AML with less than 30% bone marrow blasts, and meet certain disease severity criteria. People with HIV, active hepatitis, prior bone marrow transplant for MDS, certain heart abnormalities, or who are pregnant would not be eligible.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

There are 2 drugs used in this treatment domain of the platform trial; ES-3000 and ASTX727. This domain is separated into 2 parts; Part 1 is dose finding and part 2 is expanding recruitment using the

There are 2 drugs used in this treatment domain of the platform trial; ES-3000 and ASTX727. This domain is separated into 2 parts; Part 1 is dose finding and part 2 is expanding recruitment using the recommended phase 2 dose (RP2D). The first cycle of the protocol treatment will include only ES-3000 (without ASTX727) to establish safety and and recommended part 2 dose of the combination. Cycle 2 onwards will be a combination of ES-3000 and standard dose of ASTX727, to identify the maximum tolerated dose (MTD) and recommended phase 2 dose of ES-3000 in combination with ASTX727. The standard dose of AST727 is 1 tablet (35 mg decitabine and 100 mg cedazuridine). In the part 1 dose finding run in study, ES-3000 (tablet) will be administered orally 3 times per day approximately every 8 hours on Days 1 to 14 of each 28-day cycle with the starting dose of 60mg TiD. Doses will increase or decrease by 20mg each dose level, depending on the findings of the safety review. Safety review by assessing adverse events will be assessed at the end of the treatment cycle. Depending on the results of the safety review, the dose may increase or decrease. From cycle 2 and onwards, subjects will receive oral ASTX727 (tablet) on days 1 to 5 of each cycle. Patients will continue treatment until reaching a defined event; unacceptable toxicity, disease progression. Drug accountability will be performed by the administering institutions to assess compliance.