Inclusion Criteria:
All the following criteria must be met for a patient to be eligible for the study:
1. Written informed consent provided prior to any study-related procedure.
2. Age ≥18 years.
3. AML diagnosis according to the 2016 World Health Organisation (WHO) classification
(Arber et al. 2016) with relapsed or refractory disease who have received no more than
3 prior lines of therapy and with no available therapy; or Myelodysplastic Syndrome
(MDS) diagnosis according to the 2016 WHO classification (Arber et al. 2016) with
high-risk disease per the Revised International Prognostic Scoring System and with
relapsed or refractory disease, who have received no more than 3 prior lines of
therapy and with no available therapy.
4. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
5. Patients must have been off anti-cancer treatment for 2 weeks or 5 half-lives,
whichever is longer. Note: Hydroxyurea is exempted if used to reduce total white blood
cell (WBC) count (see below); radiation must have been completed at least 4 weeks
prior to first dose of study drug.
6. Patients must have recovered from the toxic effects of previous treatments to at least
Grade 1, for neurotoxicity or alopecia to Grade 2.
7. Clinical laboratory parameters as follows:
1. Peripheral white blood cell (WBC) count, no upper limit at Screening, but must be
<10x10^9/L on Day 1 prior to first dose of study drug. Note: Patients with
excessive blasts may be treated with hydroxyurea until 2 days prior to first dose
of study drug to reduce WBC;
2. Platelet count >10,000/µL;
3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3x the upper
limit of normal (ULN);
4. Total bilirubin ≤1.5x ULN; and
5. Creatinine clearance ≥60 mL/min (Cockcroft-Gault formula).
8. Adequate cardiac function confirmed by left ventricular ejection fraction ≥40% as per
echocardiography.
9. Life expectancy of at least 12 weeks.
10. For females of childbearing potential (FCBP), a negative pregnancy test must be
confirmed before enrolment. FCBP must commit to using two medically accepted forms of
effective contraception during study participation and until 90 days after the last
dose of study drug. Note: Where oral contraceptives are considered, please contact the
Medical Monitor. Females must also refrain from donating blood during the same
time-period.
11. For males, an effective barrier method of contraception must be used during study
participation until 90 days after the last dose of study drug, if the patient is
sexually active with a FCBP. Males must also refrain from donating blood or sperm
during the same time-period.
12. Investigator considers the patient to be suitable for participation in the clinical
study by assessing that they:
- Understand the requirements of the clinical study and can give informed consent;
- Can comply with study medication dosing requirements and all study-related
procedures and evaluations; and
- Are not considered to be potentially unreliable and/or not cooperative.
Exclusion Criteria:
Any of the following will exclude a patient from enrolment:
1. Active central nervous system (CNS) leukemia.
2. Previous treatment with CDK8-targeted therapy.
3. Patients who have undergone major surgery within 28 days prior to first dose of study
drug.
4. Hematopoietic stem cell transplant within 120 days prior to first dose of study drug.
5. Active Grade 2-4 acute graft versus host disease (GVHD), active moderate-to-severe
chronic GVHD, or requirement for systemic immunosuppressive medications for GVHD.
6. Evidence of ongoing and uncontrolled systemic bacterial, fungal, or viral infection.
7. Known seropositivity or history of active viral infection with human immunodeficiency
virus (HIV).
8. Ongoing significant liver disease such as cirrhosis, drug-induced liver injury, active
hepatitis or chronic persistent hepatitis B and/or C.
9. Impairment of gastrointestinal function or gastrointestinal disease that may
significantly alter the absorption of SEL120 (e.g. active inflammatory bowel disease,
ulcerative disease, malabsorption syndrome, short bowel syndrome, uncontrolled nausea,
vomiting or diarrhea).
10. Ongoing drug-induced pneumonitis.
11. Concurrent participation in another investigational clinical trial.
12. Taking any medications, herbal supplements or other substances (including smoking)
that are known to be strong inhibitors or inducers of CYP1A2 or that can prolong Q
wave to T wave (QT) interval and/or cause torsade de pointes within less than 2 weeks
or 5 half-lives, whichever is shorter, prior to first dose of study drug.
13. Significant cardiac dysfunction defined as myocardial infarction within 12 months of
first dose of study drug, New York Heart Association (NYHA) Class III or IV heart
failure, uncontrolled dysrhythmias, or poorly controlled angina.
14. Personal or family history of serious ventricular arrhythmia, or QT interval corrected
for heart rate (QTc) ≥450 ms (Bazett's formula).
15. Any other prior or current medical condition, intercurrent illness, surgical history,
physical or electrocardiogram (ECG) findings, laboratory abnormalities, or extenuating
circumstance (e.g. alcohol or drug addiction) that, in the Investigator's opinion,
could jeopardize patient safety or interfere with the objectives of the study.
16. Prior history of malignancies other than AML or MDS, unless the patient has been free
of the disease for 5 years or more prior to Screening. Exceptions to the ≥5-year time
limit include history of the following:
1. basal cell carcinoma of the skin;
2. non-metastatic squamous cell carcinoma of the skin;
3. carcinoma in situ of the cervix;
4. carcinoma in situ of the breast;
5. carcinoma in situ of the bladder; and
6. incidental histological finding of prostate cancer (Tumor/Node/Metastasis [TNM]
stage of T1a or T1b).
17. Pregnant or breast-feeding females.
