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Tests treatment safety and results for Acute Myeloid Leukemia
Official title Study to Evaluate the Pharmacokinetics and Safety of Oral Decitabine and Cedazuridine in Cancer Patients With Hepatic Impairment
ClinicalTrials.gov ID: NCT04953910
What this study is testing
What is ASTX727?
ASTX727 is an investigational medicine, given as an once-daily pill taken by mouth, being studied as a potential treatment for acute myeloid leukemia.
Also referred to as Oral decitabine and cedazuridine.
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
- This is a Phase 1b, multicenter, open-label, pharmacokinetic (PK), and safety study of multiple oral doses of oral decitabine and cedazuridine (formerly known as ASTX727) as a fixed-dose combination of decitabine 35 milligrams (mg) and cedazuridine 100 mg in cancer participants with moderate and severe hepatic impairment and cancer participants with normal hepatic function as control participants. Participants with severe hepatic impairment will be enrolled only after the safety evaluation of at least 6 participants with moderate hepatic impairment has been determined and supports the enrollment of participants with severe hepatic impairment.
- Phase 1: an early, usually small safety study
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
- Able to understand and comply with the study procedures, understand the risks involved in the study, and provide legally effective informed consent...
- Participants must have a histologically or cytologically confirmed malignancy as follows:
- A solid tumor that is metastatic or unresectable and for which standard life-prolonging measures are not available. or
- AML or MDS. or
- A hematologic malignancy other than AML or MDS for which standard life-prolonging measures are not available.
You likely can't join if
- Treatment with azacitidine or decitabine within 4 weeks before screening. Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high...
- Hospitalization for more than 2 days for documented febrile neutropenia, pneumonia, sepsis, or systemic infection 30 days prior to first dose.
- Treatment with any investigational medicinal product (IMP), investigational therapy, chemotherapy, immunotherapy, or targeted therapy within 2 weeks...
- Concurrent MDS therapies, including lenalidomide, erythropoietin, cyclosporine/tacrolimus, granulocyte-colony-stimulating factor (G-CSF)...
- Administration of live (attenuated) vaccines within 4 weeks before the first administration of oral decitabine and cedazuridine until after the...
- High medical risk because of other conditions such as uncontrolled systemic diseases, active uncontrolled infections, or comorbidities that may put...
See the full eligibility criteria
Who can join
- Able to understand and comply with the study procedures, understand the risks involved in the study, and provide legally effective informed consent before the first study-specific procedure; specifically able to comply...
- Participants must have a histologically or cytologically confirmed malignancy as follows:
- A solid tumor that is metastatic or unresectable and for which standard life-prolonging measures are not available. or
- AML or MDS. or
- A hematologic malignancy other than AML or MDS for which standard life-prolonging measures are not available.
- For participants with AML/MDS only:
- Cytologically or histologically confirmed diagnosis of AML (except M3 acute promyelocytic leukemia) or MDS according to the 2008 World Health Organization (WHO) classification; or
- Participants with frontline MDS or treatment naïve AML not suitable for induction therapy (e.g., \>75 years, Eastern Cooperative Oncology Group [ECOG] performance status ≥2, severe pulmonary disorder, total bilirubin...
- Platelet count ≥25,000/per microliter (μ); and
- Absolute neutrophil count (ANC) ≥100 cells/μL.
- For participants only with hematologic malignancies other than AML or MDS, or with solid tumors:
- Platelet count ≥100,000/μL; and
- ANC ≥1000 cells/μL.
- ECOG performance status of 0 to 3.
- Hepatic function defined per the National Cancer Institute Cancer Therapy Evaluation Program (NCI CTEP) Organ Dysfunction Working Group (ODWG) as:
- Normal hepatic function (Group A): total bilirubin ≤1× ULN; aspartate aminotransferase (AST): ≤1× ULN;
- Moderate hepatic impairment (Group B): total bilirubin \>1.5 to 3 × ULN; AST: any value;
- Severe hepatic impairment (Group C): total bilirubin \>3 × ULN; AST: any value.
- Adequate renal function defined as creatinine clearance (CLcr, \>50 mL/min according to the Cockcroft-Gault equation): CLcr (mL/min) = [(140-age(years)] × weight (in kg)/ 72 × serum creatinine (in mg/dL)) × 0.85 [if...
- No major surgery within 30 days of first administration of oral decitabine and cedazuridine.
- Life expectancy of at least 3 months.
- Women of childbearing potential (according to recommendations of the Clinical Trial Facilitation Group) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
- Women of childbearing potential must agree to practice 1 highly effective contraceptive measure of birth control with low user dependency and must agree not to become pregnant for 6months after completing treatment
- Male participants with female partners of childbearing potential must agree to use a male condom and advise his partner to practice 1 highly effective contraceptive measure of birth control (user dependent or with low...
What rules you out
- Treatment with azacitidine or decitabine within 4 weeks before screening. Prior cytotoxic chemotherapy for AML except for hydroxyurea to control high white blood cell (WBC) counts.
- Hospitalization for more than 2 days for documented febrile neutropenia, pneumonia, sepsis, or systemic infection 30 days prior to first dose.
- Treatment with any investigational medicinal product (IMP), investigational therapy, chemotherapy, immunotherapy, or targeted therapy within 2 weeks or 5 half-lives, whichever is longer, before the first dose of study...
- Concurrent MDS therapies, including lenalidomide, erythropoietin, cyclosporine/tacrolimus, granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, etc. Prior treatment with these...
- Administration of live (attenuated) vaccines within 4 weeks before the first administration of oral decitabine and cedazuridine until after the follow-up visit. Other vaccines, e.g., inactivated or ribonucleic acid...
- High medical risk because of other conditions such as uncontrolled systemic diseases, active uncontrolled infections, or comorbidities that may put the participant at risk of not being able to complete 1 cycle of...
- Conditions which likely promote delayed ventricular repolarization (QT prolongation):
- QTc using Fridericia's correction (QTcF) at screening or Day -1 \>470 ms for males and \>480 ms for females. or
- History or disposition for torsades des pointes (TdP) (e.g., heart failure, hypokalemia, family history of long QT Syndrome). or
- Concomitant medications that prolong the QT/QTc interval.
- Cardiac abnormalities or unstable cardiovascular conditions:
- Unstable ischemic heart disease or severe heart failure (New York Heart Association Class III or IV). or
- Uncontrolled treated/untreated hypertension (defined as a mean of 3 repeated measurements for systolic blood pressure ≥180 millimeters of mercury (mmHg) and/or diastolic blood pressure ≥110 mmHg; current or documented...
- Known significant mental illness or other condition, such as active alcohol or other substance abuse or addiction, that in the opinion of the investigator predisposes the participant to high risk of noncompliance with...
- In participants with AML/MDS, rapidly progressive or highly proliferative disease or other criteria that render the participant at high risk of requiring intensive cytotoxic chemotherapy within the next 3 months.
- Life-threatening illness or severe organ system dysfunction, such as uncontrolled congestive heart failure or chronic obstructive pulmonary disease, or other reasons including laboratory abnormalities, that, in the...
- Untreated central nervous system (CNS) metastases. Participants with treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks before screening.
- Participants infected with human immunodeficiency virus (HIV).
- Positive blood screen for hepatitis C antibody (HCV+) and positive RNA polymerase chain reaction (PCR). Participant can be included if HCV+ but negative for RNA PCR.
- Positive blood screen for hepatitis B surface antigen (HBsAg+). Participants with positive blood screen for hepatitis B surface antibody (HBsAb+) and negative hepatitis B core antibody (HBcAb-) can be included if...
- Average intake of more than 24 units of alcohol per week for male participants and 17 units per week for female participant (1 unit of alcohol equals 10 mL of pure alcohol, i.e., approximately 250 mL of beer, 75 mL of...
- Donation or loss of more than 500 mL of blood within 60 days prior to the first study drug administration.
- Hypersensitivity to decitabine, cedazuridine, or any of the excipients in oral decitabine and cedazuridine.
The study team makes the final eligibility decision.
Where it's taking place
- Houston, Texas, United States
- Yerevan, Armenia
- Plovdiv, Bulgaria
- Vilnius, Lithuania
- Wroclaw, Poland
- Bucharest, Romania
- Cluj-Napoca, Romania
- Bratislava, Slovakia
- Barcelona, Spain
- La Rioja, Spain
- Lleida, Spain
- Madrid, Spain
- Murcia, Spain
- Valencia, Spain
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 Houston, Texas, United States; Yerevan, Armenia; Plovdiv, Bulgaria; Vilnius, Lithuania; Wroclaw, Poland; Bucharest, Romania and 8 more location(s). 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.