Safety and Efficacy of RVU120 for Treatment of Relapsed/Refractory AML

Acute Myeloid Leukemia (AML) Clinical Trial

— RIVER-52  

Official title:

A Multicenter, Open-Label Clinical Trial of RVU120 in Patients With Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia With or Without NPM1 Mutation (RIVER-52)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06268574
• Other study ID #: RIVER-52
• Status: Recruiting
• Phase: Phase 2
• Start date: January 23, 2024
• Est. completion date: September 2026

Study information

• Verified date: June 2024
• Source: Ryvu Therapeutics SA
• Contact: Head of Clinical Operations
• Phone: +48-538-898-766
• Email: clinicaltrials[@]ryvu.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this study is to assess the safety, tolerability, anti-tumor activity (efficacy), pharmacokinetics (PK), and pharmacodynamics (PD) of the agent RVU120 when administered to adult patients with relapsed or refractory acute myeloid leukemia (AML) or relapsed or progressing high-risk myelodysplastic syndrome (HR-MDS) and who have no alternative therapies available. The study consists of two parts. Part 1 will assess the safety and tolerability of the dosages given and the level of anti-tumor activity or clinical response. Based on the results from part 1 the study will continue to enrol patient into Part 2 which will continue to evaluate safety and tolerability and anti-tumor activity in a larger number of patients.

Description:

Patients entering the study will undergo a Screening Period of up to 21 days, a Treatment Period where they will take the drug every other day (7 times in 13 days) in cycles of 21 days, an End of Treatment period (lasting approximately 30 days after last dose), and a 1-year Follow-up Period where participants will be contacted every 3 months for progression and survival status. In Part 1, patients with AML or HR-MDS will be enrolled. All patients will receive RVU120 until the patient meets eligibility for transplant, until there is disease progression or if there are signs of intolerance. A patient may withdraw from the study at any time at their own request or may be withdrawn at any time at the discretion of the Investigator. Depending on the outcome of part 1, part 2 may include patients with HR-MDS and AML irrespective of NPM1 mutation status.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 94
• Est. completion date: September 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects must sign a written informed consent document and complete study related procedures

• Patients must have a diagnosis of AML or HR-MDS (per 2022 WHO classification) with MDS confirmed as high risk with IPSS-R

• Patients must have relapsed or refractory AML (per ELN 2022 criteria)

• Patients must have relapsed or progressing HR-MDS (per IWG response criteria)

• Patients must have failed first-line treatment and have no alternative therapeutic options likely to produce clinical benefit

• Patients must have ECOG performance status of 0 to 2

• Patients must have adequate end organ function defined as:

1. WBC < 30 x 10(9)/L on Day 1 prior to first dose of study drug

2. Platelet count > 10,000/mcL on Day 1 prior to first dose of study drug

3. Serum albumin = 25 g/L (2.5 g/dL)

4. Normal coagulation (elevated international normalized ratio [INR], prothrombin time or activated partial thromboplastin time [APTT] <1.3 x the upper limit of normal [ULN] acceptable)

5. AST (aspartate transaminase) and ALT (alanine transaminase) = 3 x ULN (upper limit of normal)

6. Total bilirubin = 3 x ULN

7. Creatinine clearance (Cockcroft & Gault formula) = 30 mL/min

Exclusion Criteria:

• Active central nervous system (CNS) leukemia.

• Diagnosis of acute promyelocytic leukemia (APL), the M3 subtype of AML.

• Previous treatment with CDK8 and/or CDK19-targeted therapy.

• 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, =Grade 2 acute graft versus host disease (GVHD), active moderate-to-severe chronic GVHD, or requirement for systemic immunosuppressive medications for GVHD

• Evidence of ongoing and uncontrolled systemic bacterial, fungal, or viral infection and acute inflammatory conditions (including pancreatitis).

• Known seropositivity or history of active viral infection with human immunodeficiency virus (HIV).

• 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 may interfere with the metabolism of the study drug

• 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, poorly controlled angina or left ventricular ejection fraction (LVEF) <40% as per echocardiography or multiple gated acquisition (MUGA) scan.

• History of ventricular arrhythmia, or QTc =470 ms (Bazett's formula).

• Prior history of malignancies other than AML, unless the participant has been free of the disease for 5 years or more prior to Screening

• Pregnant or breast-feeding.

Related Conditions & MeSH terms

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

Intervention

Drug:
• RVU120
RVU120 is a potent, selective inhibitor of CDK8 and its paralog CDK19

Locations

Country	Name	City	State
Italy	Azienda Ospedaliero Universitaria Delle Marche	Ancona
Italy	Univerisity of Bologna Policlinico Sant'Orsola	Bologna
Italy	Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia	Brescia
Italy	Careggi University Hospital	Florence
Italy	Ospedale Vito Fazzi Lecce	Lecce
Italy	Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.	Meldola
Italy	ASST Grande Ospedale Metropolitano Niguarda	Milan
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera Policlinico Universitario Tor Vergata	Roma
Italy	Humanitas Mirasole S.p.A.	Rozzano
Italy	Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino	Turin
Poland	Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej	Biala Podlaska
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy	Gliwice
Poland	Pratia Hematologia Sp. z o.o.	Katowice
Poland	Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Kielcach	Kielce
Poland	Szpital Wojewodzki Im. Dr. Ludwika Rydygiera w Suwalkach	Suwalki
Poland	MICS Centrum Medyczne Torun	Torun
Poland	Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego	Walbrzych
Poland	Instytut Hematologii I Transfuzjologii	Warsaw
Poland	Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy	Warsaw
Poland	MTZ Clinical Research	Warszawa	Mazowieckie Województwo
Poland	Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii	Wroclaw
Poland	Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Poland	Szpital Uniwersytecki Imienia Karola Marcinkowskiego w Zielonej Gorze Sp. z o. o.	Zielona Góra

Sponsors (1)

Lead Sponsor	Collaborator
Ryvu Therapeutics SA

Countries where clinical trial is conducted

Italy,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Remission (CR), with and without measurable residual disease (MRD)	Rate of CR, CRh, or CRi	12 months
Secondary	Overall response rate	Overall response rate including CR, CRh, CRi, MLFS, or PR in AML patients or CR, PR, or marrow CR HR-MDS patients	12 months
Secondary	Duration of response	Time from first response to hematologial replase or death	12 months
Secondary	Progression-free survival	Time from first treatment to the first occurrence of disease progression or death	12 months
Secondary	Overall survival	Time from first treatment to death	12 months
Secondary	Incidence of Adverse Events (Safety and Tolerability)	Number and grade of adverse events assessed by CTCAE v5.0	Up to 24 months
Secondary	Percentage of participants bridged to hematopoietic stem cell transplantation	Number of hematopoietic stem cell transplantations following response	12 months
Secondary	Maximum Plasma Concentration (Cmax)	Assessment of the peak plasma concentration (Cmax)	12 months
Secondary	Maximum Plasma Concentration (Tmax)	Assessment of the time to peak plasma concentration (Tmax)	12 months
Secondary	Area Under the Concentration Time-Curve (AUC)	Assessed of the area under the plasma concentration versus time curve (AUC)	12 months
Secondary	Impact of treatment on hematological malignancy patient-reported outcomes (HM-PRO)	Assess changes in summary scores of the HM-PRO using a three point impact scale (Not at all, A little, A lot) and a three-point severity scale (Not at all, Mild, Severe)	Up to 12 months
Secondary	Impact of treatment on health-related quality of life (QOL-E)	Assess changes in summary scores of the QOL-E questionnaires using a four point scale in order of impact or severity from better to worse outcome (eg, Never, Rarely, Sometimes, Often)	Up to 12 months