A phase II, open-label, multicenter study of orally administered RVU120 for the treatment of anemia in patients with lower-risk myelodysplastic neoplasms (MDS)
- Conditions
- Anemia in patients with very low, low or intermediate risk myelodysplastic neoplasms (MDS)Therapeutic area: Diseases [C] - Neoplasms [C04]Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]
- Registration Number
- CTIS2023-509947-29-00
- Lead Sponsor
- GCP-Service International West GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 45
1. Written informed consent provided prior to any study-related procedure, 6. No available option of an approved MDS therapy according to decision of the treating physician and based on the following: Patients must be • ESA exposed (and refractory or intolerant) or ESA naïve and serum erythropoietin level >200 U/L AND/OR • Luspatercept exposed (and refractory or intolerant) or luspatercept naïve and not eligible for treatment (e.g. not approved) AND/OR • Lenalidomide exposed (and refractory or intolerant) or lenalidomide naïve and not eligible for treatment (e.g. due to non-presence of del(5q)), 7. Eastern Cooperative Oncology Group (ECOG) performance score of 0-2, 8. Patients must have been off anti-cancer treatment for 2 weeks or 5 half-lives, whichever is longer. Anti-cancer treatment also includes lenalidomide and luspatercept., 9. Clinical laboratory parameters as follows: • Peripheral white blood cell (WBC) count, no upper or lower limit at screening, but must be <10 x 109/L prior to first dose of study drug • Platelets count >25,000/µL • Serum albumin = 30 g/L (3.0 g/dL) • Normal coagulation (elevated INR, prothrombin time or APTT <1.3 x ULN acceptable) • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3 x the upper limit of normal (ULN) • Total bilirubin =1.5 x ULN • Creatinine clearance =30 mL/min • Urine protein < 2+ (as measured by dipstick) or =1000 mg/24 hours urine, 10. Adequate cardiac function confirmed by left ventricular ejection fraction (LVEF) =40% as per echocardiography or MUGA (Multiple Gated Acquisition) scan. In Germany, an echocardiogram will be performed (not MUGA scan)., 11. For males, an effective barrier method of contraception must be used during study participation until 28 weeks (6.5 months) after the last dose of study drug, if the patient is sexually active with a female of childbearing potential (FCBP). Males must also refrain from donating blood or sperm during the same time-period., 12. Investigator considers the patient 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; and • Are not considered to be potentially unreliable and/or not cooperative, 13. Has received all Coronavirus disease-19 (COVID-19) vaccinations per relevant national guidelines., 2. Age =18 years, 3. Diagnosis of de novo myelodysplastic neoplasms (MDS) according to WHO 2022 criteria. Diagnosis will be confirmed during screening assessment., 4. Very low, low or intermediate risk disease MDS with up to 3.5 points according to International Prognostic Scoring System Score Revised (IPSS-R) classification (to be confirmed during screening assessment). Patients with del(5q) and max. one further abnormality (excluding monosomy 7, del(7q), TP53mut) are eligible., 5. Symptomatic anemia: Symptomatic anemia (all NTD, LTB, or HTB) has to be documented in the 16 weeks baseline period ending on the day of the first IMP dose. Patients should be registered only if it is expected at time of registration that • a valid and complete Hb (at least five measurements in the period of 16 weeks before the first dose of IMP) and transfusion history will be available at inclusion AND • •the Hb Mean over the baseline period (the 16 weeks before the first dose of IMP) will be less than 10 g/dL OR three or more RBC-transfusi
1. Inability to swallow and retain oral medications., 18. 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. Any exception should be discussed with the Coordinating Investigator., 2. Patient does not accept bone marrow sampling during screening and after the treatment., 19. Personal or family history of serious ventricular arrhythmia, or QT interval corrected for heart rate (QTc) =470 ms., 20. 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 patient safety or interfere with the objectives of the study., 21. Prior history of malignancies other than AML or MDS, unless the patient has been free of the disease for 5 years or more prior to screening. The following conditions are exempt from the =5-year time limit, but the patient needs to be free disease before inclusion in the study: • 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 [TNM] stage of T1a or T1b)., 22. Females of child-bearing potential including pregnant or breast-feeding females. FCBP is defined in this protocol as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)., 3. Prior treatment with azacitidine (injectable or oral) or decitabine., 4. The patient medically requires treatment with the following drugs that are forbidden during the trial or was exposed to one of these 14 days before the first dose of the IMP: • Erythropoiesis stimulating agent (ESA) or luspatercept • Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) • Lenalidomide • Another investigational drug or device, or approved therapy for investigational use, 5. Iron chelation therapy NOTE: if therapy was initiated 56 days or more prior to the first dose of the IMP, patient can be included. Recently initiated iron chelation [< 56 days prior to registration] might influence interpretation of hematological response after start of trial medication., 6. Previous treatment with CDK8-targeted therapy(s)., 10. Prior hematopoietic stem cell transplantion., 7. Active central nervous system (CNS) involvement., 8. Patients who have undergone major surgery within 28 days prior to first dose of study drug., 9. Evidence of ongoing and uncontrolled systemic bacterial, fungal, or viral infection and acute inflammatory conditions (including pancreatitis), 11. Known seropositivity or history of active viral infection with human immunodeficiency virus (HIV)., 12. Ongoing significant liver disease such as cirrhosis, drug-induced liver injury, active hepatitis or chronic persistent hepatitis B and/or C: • Positive serologic or PCR test results for acute or chronic HBV infection. Patients whose HBV infection status cannot be determined b
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