Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This first-in-human study will evaluate RVU120 (SEL120), a novel small molecule CDK8/19
inhibitor, in patients with Acute Myeloid Leukemia (AML) or High-risk Myelodysplastic
Syndrome (HR-MDS), in terms of selection of the recommended dose for further clinical
development and assessment of safety, tolerability, preliminary anti-leukemic activity, as
well as pharmacokinetic and pharmacodynamic profiles.
Phase
Phase 1
Funding Agency/Sponsor
Industrial
Disease
Leukemia/heme
Enrollment Eligibility
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 with no available therapy who
have exhausted the applicable standard of care; 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 (IPSS-R >4.5) and with
relapsed or refractory disease with no available therapy who have exhausted the
applicable standard of care.
4. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
5. Patients must have been off anti-cancer treatment prior to study.
6. Patients must have recovered from the toxic effects of previous treatments.
7. Peripheral white blood cell (WBC) count <10x10^9/L; Platelet count >10,000/μL; Serum
albumin ≥ 30g/L (3.0g/dL); Normal coagulation (elevated INR, prothrombin time or APTT
<1.3 x ULN acceptable); AST and ALT ≤3x ULN; Total bilirubin ≤1.5 x ULN; Creatinine
clearance ≥60 mL/min (Cockcroft-Gault formula);
8. Adequate cardiac function
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 use a highly effective method of
contraception during study participation and until 6 months after the last dose of
study drug. Females must also refrain from donating blood or egg (ovum) during the
same time period.
11. For males, an effective barrier method of contraception must be used during study
participation until 6 months 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
Exclusion Criteria:
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 acute graft versus host disease (GVHD)
6. Infections and acute inflammatory conditions
7. Known seropositivity or history of HIV
8. Known positive test of / or known active diagnosis of COVID-19 viral infection
9. Ongoing significant liver disease
10. Impairment of gastrointestinal function or gastrointestinal disease
11. Ongoing drug-induced pneumonitis.
12. Concurrent participation in another investigational clinical trial.
13. 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 5
half-lives, prior to first dose of study drug.
14. Significant cardiac dysfunction or poorly controlled angina.
15. Currently taking drugs that are documented, in the drug package insert, to have a risk
of causing prolonged QTc or torsades de pointes (TdP) within 5 half-lives prior to
first dose of study drug.
16. Personal or family history of serious ventricular arrhythmia, or QT interval corrected
for heart rate (QTc) ≥470 ms (Bazett's formula).
17. Any other prior or current medical condition or extenuating circumstance that, in the
Investigator's opinion, could jeopardize patient safety or interfere with the
objectives of the study.
18. 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.
19. Pregnant or breast-feeding females.