Evaluation of metformin effects in patients with primary myelofibrosis, post-polycythemia vera and and post-essential thrombocythemia

Not Applicable

Recruiting

• Conditions: Chronic myeloproliferative disease; D47.1

• Registration Number: RBR-5g38dt
• Lead Sponsor: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-12-17
• Last Update Posted: 29 May 2023

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: Not specified

Inclusion Criteria

Patients over 18 years. Patients who were diagnosed with primary myelofibrosis, post-polycythemia vera and post-essential thombocythemia according to the World Health Organization in 2017, regardless of JAK2 mutation. Patients who are not taking another medication for the treatment of myelofibrosis or who have received treatment for myelofibrosis within 6 weeks prior to study drug initiation. Patients with oral access to the drug. Patients with life expectancy more or equal to 6 months. Palpable spleen measuring 5 cm or more below costal margin. Peripheral blood counts less or equal to 10%. ECOG less or equal to 2. Glomerular filtration rate (GFR) greater or equal to 60mL/min. Adequate liver function (AST or ALT at levels not exceeding 3x the upper limit of normal, total bilirubin at levels not higher than 2x the upper limit of normal). Negative pregnancy test prior to study initiation and agreement on contraceptive use for women of childbearing age.

Exclusion Criteria

Patients with known hypersensitivity and / or prior therapy with metformin or its excipients. Diabetes mellitus requiring use of insulin and another oral antidiabetic agent. Human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C (HCV) (except for chronic infections treated or cured for HBV and HCV, which will be accepted). Concomitant use of all herbal supplements during the study (including but not limited to St. John's wort, kava, None, gingko biloba, dehydroepiandrosterone [DHEA], or ginseng) is prohibited. Megestrol acetate (Megace) or medroxyprogesterone if used as an appetite stimulant is allowed. Uncontrolled conditions due to intercurrent illness, including, but not limited to, ongoing or active infection, refractory systemic hypertension, symptomatic congestive heart failure (New York Heart Association [NYHA] class III functional classification), unstable angina pectoris, cardiac arrhythmia, or psychiatric / social disease that would limit compliance with study requirements. Previous neoplasms, except for skin carcinomas for more than 2 years. Pregnant or breastfeeding patients. Any major surgery, extensive radiotherapy, delayed toxicity chemotherapy, biological therapy, or immunotherapy within 6 weeks prior to clinical trial screening. Any prior or concomitant use of another JAK2 inhibitor. Any investigational medication other than study drug in the 6 weeks prior to the first dose of study drug. Use of hydroxyurea, interferon, prednisone, thalidomide, busulfan, lenalidomide, anagrelide within 6 weeks prior to the first dose of study drug. Hematopoietic growth factor receptor agonists (eg erythropoietin (Epo), granulocyte colony stimulating factor (GCSF), romiplostim, eltrombopag) should not be used as they may be associated with increases in spleen size. Growth factors should not have been used for at least 6 weeks before the first dose of study drug.

Study & Design

• Study Type: Intervention
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Primary efficacy outcome: Reduction of greater or equal to 35% in spleen volume from initiation of treatment to week 24, as measured by abdomen non-contrast-enhanced computed tomography or magnetic resonance imaging.<br>Method used for quantification / evaluation: spleen volume measured by non-contrast-enhanced computed tomography or magnetic resonance imaging of the abdomen; 35% or greater reduction in spleen volume is expected in at least 1 of 10 patients included in phase 1, and at least 2 of 15 patients at the end of phase 2.;Primary safety and tolerability outcome: Safety and tolerability to treatment will be assessed by monitoring the frequency, duration and severity of adverse events from anamnesis, physical examination, and biochemical, serological, hematological test results.<br>Method used for quantification / evaluation: The severity of each adverse event will be rated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE Version 5.0).