Eltrombopag for Myelodysplastic syndromes|Thrombocytopenia

Inclusion criteria

• {"criterion_text":"- Adult subjects (18 years of age or older) with low or intermediate-1 IPSS risk MDS and stable disease.\n- Subject is practicing an acceptable method of contraception. Female subjects (or female partners of male subjects) must either be of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal >1 year), or of childbearing potential and use of an highly effective method of contraception from 2 weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study.\n- Subjects must have a platelet count taken within the 4 weeks prior to randomization that is <30 Gi/L.\n- Subjects must be ineligible or relapsed or refractory to receive other treatment options (such as azacitidine or lenalidomide) and must be ineligible to receive intensive chemotherapy or autologous/allogeneic stem cell transplantation.\n- Subjects must have platelet count and platelet transfusion data available over a period of 8 weeks prior to randomization.\n- During the 2 months prior to randomization, subjects must have a baseline BM examination which includes cytomorphology and cytogenetics. Histopathology should be performed.\n- Erythropoiesis-stimulating agents (ESAs) in anemic subjects or granulocyte colony stimulating factor (G-CSF) in subjects with severe neutropenia and recurrent infections are allowed during the study as per accepted standards. Subjects who enter the study on ESAs or G-CSF should continue at the same dose schedule until the optimal dose of study medication has been established.\n- ECOG Performance Status 0-3.\n- Subject is able to understand and comply with protocol requirements and instructions.\n- Adequate baseline organ function defined by the criteria below: total bilirubin (except for Gilbert’s Syndrome) ≤ 1.5xULN ALT and AST ≤ 3xULN creatinine ≤ 2xULN albumin must not be below the lower limit of normal by more than 20%."}

Exclusion criteria

• {"criterion_text":"- MDS with intermediate-2 or high IPSS risk.\n- Treatment with an Investigational Product within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.\n- Active and uncontrolled infections.\n- Subjects infected with Hepatitis B, C or Human Immunodeficiency Virus (HIV).\n- History of treatment for cancer other than MDS with systemic chemotherapy and/or radiotherapy within the last 2 years.\n- History of treatment with romiplostim or other TPO-R agonists.\n- Pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association [NYHA] Grade III/IV), or arrhythmia known to increase the risk of thromboembolic events (e.g. persistent atrial fibrillation), or subjects with a QTc >450 msec (QTc >480 msec for subjects with Bundle Branch Block)\n- BM fibrosis that leads to an inability to aspirate marrow for assessment\n- Peripheral monocytosis > 1000/uL prior to Day 1 of study medication.\n- Leukocytosis >=25,000/uL prior to Day 1 of study medication.\n- Female subjects who are nursing or pregnant (positive serum or urine Beta-human chorionic gonadotropin [B-hCG] pregnancy test) at screening or pre-dose on Day 1.\n- Current alcohol or drug abuse."}

Primary endpoints

• {"endpoint_text":"- Phase 1. Proportion of patients obtaining CR or R during the six month treatment period.","definition_or_measurement_approach":"Proportion of patients achieving a complete response (CR) or response (R) during the six month treatment period."}
• {"endpoint_text":"- Phase 1. Safety and tolerability parameters including non-hematological laboratory Grade 3/Grade 4 toxicities, change in bone marrow blast counts from baseline and adverse events.","definition_or_measurement_approach":"Assessment of safety/tolerability via frequency of Grade 3/4 non-hematological laboratory toxicities, change in bone marrow blast counts from baseline, and adverse event reporting."}
• {"endpoint_text":"- Phase 2. Duration of platelet response.","definition_or_measurement_approach":"Duration of platelet response (measurement approach not further specified in the record)."}
• {"endpoint_text":"- Phase 1. Long-term safety and tolerability.","definition_or_measurement_approach":"Assessment of long-term safety and tolerability (specific measures and timepoints not detailed in the record)."}

Secondary endpoints

• {"endpoint_text":"- Changes in quality of life (QoL) scores.","definition_or_measurement_approach":"Quality of life measured by QoL scores (specific instrument not specified in the record)."}
• {"endpoint_text":"- Frequency of platelet transfusions during the treatment and follow-up periods.","definition_or_measurement_approach":"Count/frequency of platelet transfusions during treatment and follow-up."}
• {"endpoint_text":"- Duration of platelet transfusion independence.","definition_or_measurement_approach":"Time period of transfusion independence (measurement approach not further specified)."}
• {"endpoint_text":"- Difference in time to response (time from starting treatment to time of achievement of CR or R).","definition_or_measurement_approach":"Time from treatment start to achievement of CR or PR as measured by MDS response criteria."}
• {"endpoint_text":"- Duration of response during the treatment and follow-up periods.","definition_or_measurement_approach":"Duration of response during treatment and follow-up (specific definition not provided)."}
• {"endpoint_text":"- Incidence and severity of bleeding using the WHO Bleeding Scale.","definition_or_measurement_approach":"Incidence and severity of bleeding graded using the WHO Bleeding Scale."}
• {"endpoint_text":"- OS and LFS.","definition_or_measurement_approach":"Overall survival (OS) and leukemia-free survival (LFS); LFS events defined as death and progression to AML."}
• {"endpoint_text":"- Eltrombopag population pharmacokinetic parameters and plasma concentration data. The relationship between eltrombopag pharmacokinetics and relevant safety and efficacy endpoints will be explored, as data permit.","definition_or_measurement_approach":"Population PK parameters and plasma concentration data for eltrombopag; exploration of relationships between PK and safety/efficacy endpoints."}
• {"endpoint_text":"- Phase 1 primary endpoints have been reached and have been publish (Lancet Haematol. 2017 Mar;4(3):e127-e136)","definition_or_measurement_approach":"Statement noting prior publication of Phase 1 primary endpoints (reference provided)."}

Italy

Earliest CTIS Part Ii Submission Date

09-12-2024

Latest Decision Or Authorization Date

24-06-2025

Processing Time Days

197

Number Of Sites

9

Number Of Participants

160

Primary sponsor

Full Name

Associazione Qol-One

Organisation Type

Patient organisation/association

Country Of Registered Address

Italy