A Multicenter, Open-Label, Dose-Finding Clinical Trial to Assess the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Efficacy of RVU120 in Combination with Venetoclax in Participants with Acute Myeloid Leukemia Who Failed Prior Therapy with Venetoclax and a Hypomethylating Agent (RIVER-81)
- Conditions
- Acute Myeloid LeukemiaMedDRA version: 21.1Level: PTClassification code: 10000880Term: Acute myeloid leukaemia Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-505911-19-00
- Lead Sponsor
- Ryvu Therapeutics S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 118
Written informed consent provided prior to any study-related procedure., Must have recovered from the toxic effects of previous treatments to at least Grade 1, except for neurotoxicity (which should return at least to Grade 2 or baseline), or alopecia., Clinical laboratory parameters as follows: - Peripheral WBC count, no upper limit at Screening, but must be <25 x109/L on Day 1 prior to first dose of study drug (see acceptable methods of cytoreduction above) - Platelet count >10,000/µL at the time of first study drug administration - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3X the upper limit of normal (ULN) - Total bilirubin =3.0X ULN - Creatinine clearance =50 mL/min (Cockcroft and Gault formula; Section 10.7)., Adequate cardiac function confirmed by left ventricular ejection fraction =40% as per echocardiography., For women of childbearing potential (WOCBP), a negative pregnancy test must be confirmed during Screening and prior to first dose of =3 days prior to first dose of study drug. WOCBP must commit to using a highly effective method of contraception during study participation and until 28 weeks (approximately 6.5 months) after the last dose of RVU120 (Section 10.4) OR For males, an effective barrier method of contraception must be used during study participation and until 28 weeks (approximately 6.5 months) after the last dose of RVU120, if the participant is sexually active with a WOCBP (Section 10.4)., Agree not to donate blood, eggs (ova) or sperm, during study participation and until 28 weeks (approximately 6.5 months) after the last dose of RVU120 (Section 10.4)., Investigator considers the participant to be suitable for participation in the clinical study by assessing that they: - understand the requirements of the clinical study and can give informed consent - can comply with study medication dosing requirements and all study-related procedures and evaluations - are not considered to be potentially unreliable and/or not cooperative., Has received all Coronavirus disease-19 (COVID-19) vaccinations per relevant national guidelines., Age =18 years at time of provision of informed consent., AML diagnosis according to the 2022 World Health Organization (WHO) classification (Arber 2022)., Relapsed or refractory AML per the ELN 2022 (Döhner 2022) - Participants with <10% bone marrow cellularity may be enrolled where immunophenotyping of the bone marrow demonstrates this is due to underlying disease and not to potential myelotoxicity e.g., where >50% of cells have AML phenotype., Failed first-line treatment with Ven + HMA specified as any of the following: - Participants who do not achieve at least morphologic leukemia-free state (MLFS) or partial remission (PR), or are progressing after at least 2 cycles of Ven + HMA - Participants who do not achieve CR, CRh, or CRi, after 4 cycles of Ven + HMA - Participants relapsing any time after treatment with Ven + HMA., No alternative therapeutic options likely to produce clinical benefit., Eastern Cooperative Oncology Group (ECOG) performance score of 0-2 (Section 10.6)., Life expectancy of at least 12 weeks., No other anti-cancer treatment received for 14 days or 5 half-lives, whichever is shorter, prior to first dose of study drug.
Active central nervous system (CNS) leukemia., Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RVU120 (e.g., active inflammatory bowel disease, ulcerative disease, malabsorption syndrome, short bowel syndrome, uncontrolled nausea, vomiting or diarrhea)., Ongoing drug-induced pneumonitis., Concurrent participation in another investigational clinical trial., Taking any medications, herbal supplements, or other substances that are known to be strong inhibitors or moderate/strong inducers or sensitive substrates of CYPXXX, within less than 5 half-lives prior to first dose of study drug (Section 10.8), Taking medications, over-the-counter medications, foods or herbal supplements that are known to be strong or moderate inhibitors of CYP3A4 or P-gp, within less than 5 half-lives prior to first dose of study drug (Section 10.11). Of note, azole antifungals that are used in clinical practice for prophylaxis or maintenance are allowed, except in Cycle 1 for participants in Part 1. Rules for Ven dose adjustment are provided in Table 6., 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 (Section 10.9), or left ventricular ejection fraction (LVEF) <40% as per echocardiography or multiple gated acquisition (MUGA) scan., Taking medications that are documented in their drug package insert to have a risk of causing prolonged Q wave to T wave interval (QT) corrected for heart rate (QTc) or Torsades de pointes within 5 half-lives prior to first dose of study drug. Please also consult the following Credible Meds web page: https://crediblemeds.org/index.php/login/dlcheck (Section 10.10)., History of ventricular arrhythmia, or QTc =470 ms (Bazett’s formula; Section 10.12)., Prior history of malignancies other than AML, unless the participant has been free of the disease for 5 years or more prior to Screening, or the following apply: - basal cell carcinoma of the skin - non-metastatic squamous cell carcinoma of the skin - carcinoma in situ of the cervix - carcinoma in situ of the breast - carcinoma in situ of the bladder - incidental histological finding of prostate cancer (Tumor/Node/Metastasis stage of T1a or T1b)., Pregnant or breast-feeding., Diagnosis of acute promyelocytic leukemia (APL), the M3 subtype of AML., Any other prior or current medical condition, intercurrent illness, surgical history, physical or electrocardiogram (ECG) findings, laboratory abnormalities, or extenuating circumstance (e.g., alcohol or drug addiction) that, in the Investigator’s opinion, could jeopardize participant safety or interfere with the objectives of the study., 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 such as cirrhosis, dr
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method