RVU120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome

Acute Myeloid Leukemia Clinical Trial

Official title:

A Phase Ib Study of RVU120 (SEL120) in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04021368
• Other study ID #: CLI120-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 4, 2019
• Est. completion date: December 30, 2024

Study information

• Verified date: January 2024
• Source: Ryvu Therapeutics SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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.

Description:

The study will determine the recommended phase II dose (RP2D) and safety of RVU120 (SEL120) given as monotherapy over a range of dose-levels, following a closely controlled dose escalation study design.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 112
• Est. completion date: December 30, 2024
• Est. primary completion date: December 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• High-risk Myelodysplastic Syndrome
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• RVU120(SEL120)
RVU120(SEL120) will be administered as a single oral dose every other day (q.o.d.) for a total of 7 doses i.e. on Days 1, 3, 5, 7, 9, 11 and 13, in a 3-week treatment cycle.

Locations

Country	Name	City	State
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Swietokrzyskie Centrum Onkologii, Klinika Hematologii i Transplantacji Szpiku	Kielce	Swietokrzyskie
Poland	MICS Centrum Medyczne Torun	Torun
Poland	Instytut Hematologii i Transfuzjologii	Warsaw
Poland	Dolnoslaskie Centrum Onkologii, Pulmonologii i Hematologii	Wroclaw
United States	Northside Hospital	Atlanta	Georgia
United States	MD Anderson Cancer Center	Houston	Texas
United States	Sylvester Comprehensive Cancer Center, University of Miami Hospital and Clinics	Miami	Florida
United States	Tennessee Oncology	Nashville	Tennessee
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Ryvu Therapeutics SA

Countries where clinical trial is conducted

United States,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	AML surface markers	Pharmacodynamic profile of RVU120(SEL120) will be characterized using immunophenotyping of AML surface markers by exploratory assay.	Up to 2 years
Other	Phosphorylated protein levels in AML blasts	Pharmacodynamic profile of RVU120(SEL120) will be characterized using phosphorylated protein levels in AML blasts by exploratory immunoassay.	Up to 2 years
Other	Transcriptomic profile changes in AML blasts	Pharmacodynamic profile of RVU120(SEL120) will be characterized using transcriptomic profile changes in AML blasts by exploratory next generation sequencing.	Up to 2 years
Other	Genetic profile changes in AML blasts	Pharmacodynamic profile of RVU120(SEL120) will be characterized using genetic profile changes in AML blasts by next generation sequencing.	Up to 2 years
Primary	Recommended dose (RD)	The RD will be determined using all available data, which will include dose limiting toxicities (DLTs) and other toxicities, signs of anti-leukemic activity, pharmacokinetic and pharmacodynamic characteristics.	Up to 2 years
Primary	Incidence of Adverse Events (Safety and Tolerability)	Safety and tolerability profile will be assessed by Common Terminology Criteria for Adverse Events v5.0 and summarized by type, frequency, and severity of adverse events.	Up to 2 years
Secondary	The Maximum Observed Concentration (C[max])	Pharmacokinetic profile of RVU120(SEL120) will be characterized using the Maximum Observed Concentration (C[max]).	Up to 2 years
Secondary	The Terminal Half-life (t[1/2])	Pharmacokinetic profile of RVU120(SEL120) will be characterized using the Terminal Half-life (t[1/2]).	Up to 2 years
Secondary	The Area Under the Curve (AUC)	Pharmacokinetic profile of RVU120(SEL120) will be characterized using the Area Under the Curve (AUC).	Up to 2 years
Secondary	The Volume of Distribution at Steady State (Vss)	Pharmacokinetic profile of RVU120(SEL120) will be characterized using the Volume of Distribution at Steady State (Vss).	Up to 2 years
Secondary	Anti-leukemic activity	Anti-leukemic activity will be assessed by AML or MDS Response Criteria (Döhner et al., 2017, or Cheson et al., 2006, respectively).	Up to 2 years