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New treatment option for Myelodysplastic Syndromes
Official title Combined Evaluation of Epigenetic and Sensitising Therapy in AML and MDS
ClinicalTrials.gov ID: NCT05636514
What this study is testing
What is Decitabine/Cedazuridine 35 Mg-100 Mg ORAL TABLET?
Decitabine/Cedazuridine 35 Mg-100 Mg ORAL TABLET is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for myelodysplastic syndromes.
Also referred to as ASTX727, INQOVI.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The goal of this project is to see if two new potential treatments (defactinib and the combination tablet of decitabine/cedazuridine) can safely be combined to improve outcomes in people with high-risk myelodysplastic syndrome (MDS), certain forms of Acute Myeloid Leukaemia (AML), and Chronic Myelomonocytic Leukaemia (CMML). Decitabine/cedazuridine is approved for use by the Australian Therapeutics Goods Administration (TGA) as treatment for MDS.
- Phase 1: an early, usually small safety study
- You might receive a placebo (an inactive treatment) instead of the study drug.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Participants must meet all of the following criteria at the time of screening:
- Age ≥ 18 years
- Documented diagnosis of:
- Myelodysplastic syndrome (MDS) classified as intermediate-2 or high risk according to the International Prognostic Scoring System (IPSS), or
- Acute Myeloid Leukaemia (AML) with 20-30% marrow blasts and multilineage dysplasia, according to WHO classification, or
You likely can't join if
- Participants who meet any of the following criteria at the time of screening/enrolment (up to 28 days prior to Cycle 1 Day 1) will be ineligible for...
- Acute myeloid leukemia (AML) with ≥ 30% blasts in bone marrow according to WHO classification.
- Prior allogeneic or autologous stem cell transplant.
- Prior receipt of \>1 cycle of a hypomethylating agent.
- Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.
- Use of any of the following within 28 days prior to cycle 1 day 1:
See the full eligibility criteria
Who can join
- Participants must meet all of the following criteria at the time of screening:
- Age ≥ 18 years
- Documented diagnosis of:
- Myelodysplastic syndrome (MDS) classified as intermediate-2 or high risk according to the International Prognostic Scoring System (IPSS), or
- Acute Myeloid Leukaemia (AML) with 20-30% marrow blasts and multilineage dysplasia, according to WHO classification, or
- Chronic myelomonocytic leukemia (CMML) with 10-29% marrow blasts without myeloproliferative disorder according to World Health Organisation (WHO) classification. This confirmation will be from either the Bone marrow...
- Performance status by Eastern Cooperative Oncology Group (ECOG) Criteria of 0 or 1
- Unsuitable for allogeneic stem cell transplantation
- For participants who were born female who are of childbearing potential (FCBP) the following criteria apply:
- Agreement to use at least two highly effective (per Clinical Trial Facilitation Group) contraceptive methods throughout the study, and for 6 months following the last dose of study drug:
- Oral/intravaginal/transdermal combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
- Oral/injectable/implantable progestogen-only hormonal contraception associated with inhibition of ovulation
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Bilateral tubal occlusion
- Vasectomised partner
- Sexual abstinence and
- Confirmation of a negative serum pregnancy test at screening.
- Male participants with a partner who was born female and is of childbearing potential must agree to use at least two highly effective (per Clinical Trial Facilitation Group) contraceptive methods throughout the course...
- Provision of signed written informed consent document prior to any study related assessments or procedures being carried out.
What rules you out
- Participants who meet any of the following criteria at the time of screening/enrolment (up to 28 days prior to Cycle 1 Day 1) will be ineligible for entry into the study:
- Acute myeloid leukemia (AML) with ≥ 30% blasts in bone marrow according to WHO classification.
- Prior allogeneic or autologous stem cell transplant.
- Prior receipt of \>1 cycle of a hypomethylating agent.
- Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS leukemia.
- Use of any of the following within 28 days prior to cycle 1 day 1:
- thrombopoiesis-stimulating agents ([TSAs]; eg, Romiplostim, Eltrombopag, Interleukin-11)
- ESAs (Erythropoiesis stimulating agent) and other RBC (Red blood cell) hematopoietic growth factors (eg, interleukin-3)
- Any other investigational medicinal product from another clinical trial.
- Exposure to any medication, supplement, traditional/herbal medicine, or food with potential for drug-drug interactions with defactinib during the course of the study. This includes:
- strong CYP3A4 inhibitors or inducers
- strong CYP2C9 inhibitors or inducers
- P-glycoprotein (P-gp) inhibitors or inducers
- Treatment with warfarin. Patients on warfarin can be converted to low molecular-weight heparin or direct oral anticoagulants (DOACs). Participants unwilling or unable to convert to an alternative are not eligible.
- Use of hydrea for more than 7 days prior to cycle 1 day 1. Use within that time period is permissible.
- Concurrent use of corticosteroids unless the participant is on a dose of ≤10mg prednisolone or equivalent for medical conditions other than MDS.
- Active inflammatory bowel disease, or any other gastrointestinal disorder or defect that would interfere with the ingestion, absorption, distribution, metabolism or excretion of the investigational products and/or...
- Prior history of malignancies, other than MDS unless the participant has been free of the disease for ≥ 12 months. However, participants with the following history/concurrent conditions are allowed:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)
- Significant active cardiac disease within the previous 6 months, including:
- New York Heart Association (NYHA) class III or IV congestive heart failure;
- Unstable angina or angina requiring surgical or medical intervention; and/or
- Myocardial infarction
- Baseline Qt interval greater than 440 milliseconds (males) or 450 milliseconds (females)
- Active systemic infection:
- Infection with ongoing signs/symptoms related to the infection without improvement despite appropriate anti- infectives
- Active Hepatitis B (HBV) infection (defined as HBsAg positive, or HBcAb positive and measurable HBV DNA; participants who are HBcAb positive must have HBV DNA assayed during screening)
- Participants with Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV) infection will be considered individually by the coordinating principal investigator:
- Those with HIV will generally be eligible if receiving antiretroviral therapy, HIV viral load (VL) is suppressed \<50 copies/mL , and CD4≥350 cells/mm3.
- Those with HCV will generally be eligible if there is no evidence of clinical hepatic dysfunction or other systemic manifestations of HCV disease and the hepatic parameters below are met. Consideration should be given...
- Any of the following laboratory abnormalities:
- Serum AST/SGOT (Aspartate transaminase / Serum glutamic oxaloacetic transaminase) or ALT/SGPT (Alanine aminotransaminase / Serum glutamic pyruvate transaminase) \> 2.5 x ULN (upper limit of normal)
- Serum total bilirubin \> 1.5 x ULN. Patients with Gilbert syndrome may enroll if total bilirubin \< 51 umol/L upon discussion with the coordinating investigator
- Evidence of autoimmune hemolytic anemia manifested as a corrected reticulocyte count of \> 2% with either a positive direct anti-globulin test (DAT) or over 50% of indirect bilirubin
- Creatinine clearance \<50 ml/minute as calculated by the CockcroftGault formula or serum creatinine of ≥ 1.5 x ULN.
- Absolute WBC (white blood cell count) ≥ 20 x 109/L f ) Participants with isolated individual lab abnormalities considered to be disease related will be considered individually in consultation with the Coordinating...
- Known or suspected hypersensitivity to study drugs or their constituents.
- Pregnant or breast-feeding.
- Any condition not already outlined above which, in the opinion of the clinical investigator, would place the participant at risk if they participated or would jeopardise adherence or follow up or confound the ability to...
The study team makes the final eligibility decision.
Where it's taking place
- Sydney, New South Wales, Australia
- Westmead, New South Wales, Australia
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Sydney, New South Wales, Australia; Westmead, New South Wales, Australia. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.