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

NCT04021368 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: CLI120-001
• Study Type: interventional
• Target: 112
• Locations: 2 countries
• Sites: 10

Brief 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.

Conditions

Acute Myeloid Leukemia; High-risk Myelodysplastic Syndrome

Keywords

Acute Myeloid Leukemia; Myelodysplastic Syndrome; CDK8/19 Inhibitor; RVU120 (SEL120); Clinical Trial, Phase Ib

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (5)

• The Maximum Observed Concentration (C[max])

  Up to 2 years

• The Terminal Half-life (t[1/2])

  Up to 2 years

• The Area Under the Curve (AUC)

  Up to 2 years

• The Volume of Distribution at Steady State (Vss)

  Up to 2 years

• Anti-leukemic activity

  Up to 2 years

Other Outcomes (4)

• AML surface markers

  Up to 2 years

• Phosphorylated protein levels in AML blasts

  Up to 2 years

• Transcriptomic profile changes in AML blasts

  Up to 2 years

Study Arms (1)

RVU120(SEL120)

EXPERIMENTAL

The first part of the study consists of dose-escalation cohorts where patients will receive ascending doses of RVU120(SEL120) to determine the recommended dose (RD) for further clinical development. The second part of the study is an enrichment cohort where additional 6 to 20 patients will be treated with RVU120(SEL120) to support the evaluation of the RD.

Drug: RVU120(SEL120)

Interventions

RVU120(SEL120) DRUG

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.

RVU120(SEL120)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All the following criteria must be met for a patient to be eligible for the study:
• Written informed consent provided prior to any study-related procedure.
• Age ≥18 years.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-2.
• Patients must have been off anti-cancer treatment prior to study.
• Patients must have recovered from the toxic effects of previous treatments.
• 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);
• Adequate cardiac function
• Life expectancy of at least 12 weeks.
• 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.
• 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.
• Investigator considers the patient to be suitable for participation in the clinical study

You may not qualify if:

• Active central nervous system (CNS) leukemia.
• Previous treatment with CDK8-targeted therapy.
• Patients who have undergone major surgery within 28 days prior to first dose of study drug.
• Hematopoietic stem cell transplant within 120 days prior to first dose of study drug.
• Active acute graft versus host disease (GVHD)
• Infections and acute inflammatory conditions
• Known seropositivity or history of HIV
• Known positive test of / or known active diagnosis of COVID-19 viral infection
• Ongoing significant liver disease
• Impairment of gastrointestinal function or gastrointestinal disease
• Ongoing drug-induced pneumonitis.
• Concurrent participation in another investigational clinical trial.
• 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.
• Significant cardiac dysfunction or poorly controlled angina.
• 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.

Sponsors & Collaborators

• Ryvu Therapeutics SA: lead

Study Sites (10)

Sylvester Comprehensive Cancer Center, University of Miami Hospital and Clinics

Miami, Florida, 33136, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

MICS Centrum Medyczne Toruń

Torun, 87-100, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

Location

Dolnośląskie Centrum Onkologii, Pulmonologii i Hematologii

Wroclaw, 53-413, Poland

Location

Świętokrzyskie Centrum Onkologii, Klinika Hematologii i Transplantacji Szpiku

Kielce, Świętokrzyskie Voivodeship, 25-734, Poland

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalating Cohorts with a safety expansion Cohort

Study Record Dates

• First Submitted: July 12, 2019
• First Posted: July 16, 2019
• Study Start: September 4, 2019
• Primary Completion: December 30, 2024
• Study Completion: December 30, 2024
• Last Updated: February 14, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

PL (5); US (5)