A Randomized, Open-Label, Phase 1-2 Study of ASTX727 Low Dose (ASTX727 LD) Extended Schedule in Subjects with Lower Risk (IPSS Low or Intermediate-1) Myelodysplastic Syndromes (MDS)
- Conditions
- ower Risk (IPSS Low or Intermediate-1) Myelodysplastic Syndromes (MDS)MedDRA version: 20.0Level: HLTClassification code 10028536Term: Myelodysplastic syndromesSystem Organ Class: 100000004851MedDRA version: 27.0Level: PTClassification code 10028533Term: Myelodysplastic syndromeSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-003281-40-DE
- Lead Sponsor
- Taiho Oncology, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 168
Inclusion Criteria
Subjects must fulfill all of the following inclusion criteria.
1) Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent before the first study-specific procedure.
2) Men or women =18 years with IPSS low risk or Int-1 MDS (all subjects). Subjects must have had at least 1 of the following disease-related criteria during the 8 weeks before randomization:
a) RBC transfusion dependence, defined as 2 or more units of RBC transfusions.*
b) Hb of =9.0 g/dL in at least 2 blood counts prior to randomization or in 1 blood count if RBC transfusion was received.
c) ANC of <0.5×109/L in at least 2 blood counts prior to randomization.
d) Platelet counts of <50×109/L in at least 2 blood counts prior to randomization.
*RBC transfusions administered for Hb levels =9.0 g/dL are counted
3) ECOG performance status of 0 to 2.
4) Adequate organ function defined as follows:
a) Hepatic: Total or direct bilirubin =2 × upper limit of normal (ULN); aspartate aminotransferase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic pyruvic transaminase (ALT/SGPT) =5 × ULN.
b) Renal: serum creatinine =1.5 × ULN or calculated creatinine clearance or glomerular filtration rate =50 mL/min.
5) Women of childbearing potential (according to recommendations of the Clinical Trial Facilitation Group [CTFG]*; CTFG 2020) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of childbearing potential and their partners must use at least 1 highly effective birth control method (with a failure rate of <1% per year; preferably with low user dependency), from the start of participation in the study and for 6 months after the last dose of study treatment. Contraceptive measures that are considered highly effective with low user dependency include implantable progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, or azoospermic partner (vasectomized or due to a medical cause) **
6) Male subjects with female partners of childbearing potential must agree to use a male condom and advise their partners to practice 1 highly effective contraceptive measure of birth control (user dependent or with low user dependency) and must agree not to father a child while receiving study treatment for at least 3 months after completing treatment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 144
Subjects meeting any of the following exclusion criteria will be excluded from the study:
1. Treatment with any investigational drug or therapy within 2 weeks before study treatment, or 5 half-lives,
whichever is longer, before the first dose of study treatment, or ongoing clinically significant AEs from previous treatment.
2. Prior treatment with azacitidine, decitabine or gaudecitabine.
3. Treatments for MDS, including erythropoietins, colony-stimulating factors (CSFs), thrombopoietins, chemotherapy, and immunosuppression including calcineurin inhibitors, glucocorticoids, etc., must be concluded 1 month prior to study treatment.
4. Diagnosis of chronic myelomonocytic leukemia (CMML).
5. Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled infections.
6. 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 subject to high risk of noncompliance with the protocol.
7. Life-threatening illness, medical condition or organ system dysfunction, or other reasons including laboratory abnormalities, which, in the investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of ASTX727 LD, or compromise the integrity of the study outcomes.
8. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer or breast cancer under control with hormone therapy, or other cancer from which the subject has been disease free for at least 1 year.
9. Known active infection with human immunodeficiency virus or hepatitis viruses.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method