Clinical trial NCT06268574: Safety and Efficacy of RVU120 for Treatment of Relapsed/Refractory AML
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Acute Myeloid Leukemia (AML)
High-risk Myelodysplastic Syndrome
Lead sponsor: Ryvu Therapeutics SA
Sponsor class: INDUSTRY
First posted: 2024-02-20
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

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 A patient may withdraw from the study at any time at their own request or may be withdrawn at any time at the discretion of the Investigator.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

Eligibility criteria: 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.

Primary outcomes:
measure: Complete Remission (CR), with and without measurable residual disease (MRD)
timeFrame: 12 months
Secondary outcomes:
measure: Overall response rate
timeFrame: 12 months
measure: Duration of response
timeFrame: 12 months
measure: Progression-free survival
timeFrame: 12 months
measure: Overall survival
timeFrame: 12 months
measure: Incidence of Adverse Events (Safety and Tolerability)
timeFrame: Up to 24 months
measure: Percentage of participants bridged to hematopoietic stem cell transplantation
timeFrame: 12 months
measure: Maximum Plasma Concentration (Cmax)
timeFrame: 12 months
measure: Maximum Plasma Concentration (Tmax)
timeFrame: 12 months
measure: Area Under the Concentration Time-Curve (AUC)
timeFrame: 12 months
measure: Impact of treatment on hematological malignancy patient-reported outcomes (HM-PRO)
timeFrame: Up to 12 months
measure: Impact of treatment on health-related quality of life (QOL-E)
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: la Tronche
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes
city: le Mans
country: France
facility: Centre Hospitalier Le Mans
city: Lille
country: France
facility: Centre Hospitalier Universitaire de Lille (CHU Lille)
city: Marseille
country: France
facility: Institut Paoli Calmettes (IPC)
city: Nice
country: France
facility: Centre Hospitalier Universitaire (CHU) de Nice - Hopital L'Archet I
city: Nimes
country: France
facility: Centre Hospitalier Universitaire de Nimes (CHU) - Institut de Cancerologie du Gard
city: Paris
country: France
facility: Publique-Hopitaux de Paris (AP-HP) - Hopital Saint-Louis
city: Rouen
country: France
facility: UNICANCER - Centre Henri-Becquerel
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Delle Marche
city: Bologna
country: Italy
facility: Univerisity of Bologna Policlinico Sant'Orsola
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
city: Florence
country: Italy
facility: Careggi University Hospital
city: Lecce
country: Italy
facility: Ospedale Vito Fazzi Lecce
city: Meldola
country: Italy
facility: Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Azienda Ospedaliera Policlinico Universitario Tor Vergata
city: Rozzano
country: Italy
facility: Humanitas Mirasole S.p.A.
city: Turin
country: Italy
facility: Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
city: Warszawa
country: Poland
facility: MTZ Clinical Research
state: Mazowieckie Województwo
city: Biala Podlaska
country: Poland
facility: Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
city: Katowice
country: Poland
facility: Pratia Hematologia Sp. z o.o.
city: Suwałki
country: Poland
facility: Szpital Wojewodzki Im. Dr. Ludwika Rydygiera w Suwalkach
city: Toruń
country: Poland
facility: MICS Centrum Medyczne Toruń
city: Warsaw
country: Poland
facility: Instytut Hematologii I Transfuzjologii
city: Warsaw
country: Poland
facility: Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
city: Wałbrzych
country: Poland
facility: Specjalistyczny Szpital Im. Dra Alfreda Sokolowskiego
city: Wrocław
country: Poland
facility: Dolnoslaskie Centrum Onkologii Pulmonologii i Hematologii
city: Zielona Góra
country: Poland
facility: Szpital Uniwersytecki Imienia Karola Marcinkowskiego w Zielonej Gorze Sp. z o. o.
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Institut Catala d'Oncologia Hospitalet
city: Cáceres
country: Spain
facility: Complejo Hospitalario De Caceres - Hospital General San Pedro De Alcantara
city: Madrid
country: Spain
facility: Hospital Universitario La Paz (HULP)
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Sevilla
country: Spain
facility: Virgen del Rocío University Hospital
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
Study officials:
References: