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

Phase 2

Recruiting

• Conditions: High-risk Myelodysplastic Syndrome; Acute Myeloid Leukemia (AML)
• Interventions: Drug: RVU120

• Registration Number: NCT06268574
• Lead Sponsor: Ryvu Therapeutics SA

Brief 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.

Detailed 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 A patient may withdraw from the study at any time at their own request or may be withdrawn at any time at the discretion of the Investigator.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.

Study Timeline

• Study First Submitted: 2024-01-05
• Study Start: 2024-01-23
• Study First Submitted QC: 2024-02-12
• Study First Posted: 2024-02-20
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-12
• Last Update Posted: 2024-12-13
• Primary Completion: 2026-02
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 94

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RVU120 single agent	RVU120	RVU120 oral capsules administered at dose of 250 mg every other day on Days 1-13 of each 21-day cycle of treatment.

Primary Outcome Measures

Name	Time	Method
Complete Remission (CR), with and without measurable residual disease (MRD)	12 months	Rate of CR, CRh, or CRi

Secondary Outcome Measures

Name	Time	Method
Overall survival	12 months	Time from first treatment to death
Maximum Plasma Concentration (Tmax)	12 months	Assessment of the time to peak plasma concentration (Tmax)
Progression-free survival	12 months	Time from first treatment to the first occurrence of disease progression or death
Overall response rate	12 months	Overall response rate including CR, CRh, CRi, MLFS, or PR in AML patients or CR, PR, or marrow CR HR-MDS patients
Duration of response	12 months	Time from first response to hematologial replase or death
Percentage of participants bridged to hematopoietic stem cell transplantation	12 months	Number of hematopoietic stem cell transplantations following response
Area Under the Concentration Time-Curve (AUC)	12 months	Assessed of the area under the plasma concentration versus time curve (AUC)
Impact of treatment on hematological malignancy patient-reported outcomes (HM-PRO)	Up to 12 months	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)
Impact of treatment on health-related quality of life (QOL-E)	Up to 12 months	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)
Incidence of Adverse Events (Safety and Tolerability)	Up to 24 months	Number and grade of adverse events assessed by CTCAE v5.0
Maximum Plasma Concentration (Cmax)	12 months	Assessment of the peak plasma concentration (Cmax)

Trial Locations

Locations (43)

L'Hotel Dieu de Quebec; 🇨🇦 Calgary, Canada

University of Alberta - Faculty of Medicine & Dentistry; 🇨🇦 Vancouver, Canada

Centre Hospitalier Universitaire Grenoble Alpes; 🇫🇷 la Tronche, France

Centre Hospitalier Le Mans; 🇫🇷 le Mans, France

Centre Hospitalier Universitaire de Lille (CHU Lille); 🇫🇷 Lille, France

Institut Paoli Calmettes (IPC); 🇫🇷 Marseille, France

Centre Hospitalier Universitaire (CHU) de Nice - Hopital L'Archet I; 🇫🇷 Nice, France

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

Centre Hospitalier Universitaire de Nimes (CHU) - Institut de Cancerologie du Gard; 🇫🇷 Nimes, France

Azienda Ospedaliero Universitaria Delle Marche; 🇮🇹 Ancona, Italy

Publique-Hopitaux de Paris (AP-HP) - Hopital Saint-Louis; 🇫🇷 Paris, France

UNICANCER - Centre Henri-Becquerel; 🇫🇷 Rouen, France

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, Italy

MTZ Clinical Research; 🇵🇱 Warszawa, Mazowieckie Województwo, Poland

Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej; 🇵🇱 Biala Podlaska, Poland

Uniwersyteckie Centrum Kliniczne; 🇵🇱 Gdańsk, Poland

Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy; 🇵🇱 Gliwice, Poland

Pratia Hematologia Sp. z o.o.; 🇵🇱 Katowice, Poland

Szpital Wojewodzki Im. Dr. Ludwika Rydygiera w Suwalkach; 🇵🇱 Suwałki, Poland

MICS Centrum Medyczne Toruń; 🇵🇱 Toruń, Poland

Instytut Hematologii I Transfuzjologii; 🇵🇱 Warsaw, Poland

Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy; 🇵🇱 Warsaw, Poland

Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego; 🇵🇱 Wałbrzych, Poland

Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii; 🇵🇱 Wrocław, Poland

Szpital Uniwersytecki Imienia Karola Marcinkowskiego w Zielonej Gorze Sp. z o. o.; 🇵🇱 Zielona Góra, Poland

Hospital de la Santa Creu i de Sant Pau; 🇪🇸 Barcelona, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Institut Catala d'Oncologia Hospitalet; 🇪🇸 Barcelona, Spain

Complejo Hospitalario De Caceres - Hospital General San Pedro De Alcantara; 🇪🇸 L'Hospitalet de Llobrega, Spain

Hospital Universitario La Paz (HULP); 🇪🇸 Madrid, Spain

Hospital Regional Universitario de Málaga; 🇪🇸 Malaga, Spain

Clinica Universidad de Navarra; 🇪🇸 Navarra, Spain

Virgen del Rocío University Hospital; 🇪🇸 Sevilla, Spain

MD Anderson Cancer Center Madrid; 🇪🇸 Madrid, Spain

Hospital Universitario La Fe; 🇪🇸 Valencia, Spain