Chronic myeloproliferative disease
Conditions
Interventions
Metformin for primary myelofibrosis patients with grade 1 to 3 bone marrow fibrosis. All eligible patients will receive the drug
placebo will not be used. There is no control group. The study will include primary myelofibrosis patients in regular follow up in the outpatient clinics of the Hematology and Hemotherapy Center of th
Drug
Sponsors
Fundação de Amparo à Pesquisa do Estado de São Paulo
Fundação de Amparo à Pesquisa do Estado de São Paulo
Eligibility
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Age superior to 18 years-old. Patients who agreed to be included in the study and have signed written-informed-consent. Primary myelofibrosis diagnosis confirmed by at least two different professionals of the Unicamp hematology-patology team. Patients capable of taking oral medicine. Glomerular filtration rate above 60 ml/min. Adequate liver function (bilirubin < 1,5x superior limit and AST/ALT < 3x superior limit). Negative pregnant test at the beginning of the study. Accepting using contraceptive methods during study duration.
Exclusion criteria
Exclusion criteria: Biguanide hypersensitivity. Diabetes mellitus diagnosis. Chronic alcohol intake. Patients who are planned to be submitted to sequential image studies using iodine contrast. Untreated vitamin B12 deficiency. Being pregnant or breastfeeding. Ongoing HIV or hepatitis B/C infection. Active autoimmune diseases. Uncontrolled comorbidities: systemic arterial hypertension, cardiac insufficiency, ischemic heart diseases, cardiac arrhythmia, chronic diarrhea. Severe psychiatric disorders or social conditions that may limit adherence to the protocol and autonomy. Anagrelide and/or Ruxolitinib use in the sixty days that precede patient´s inclusion in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Regression of bone marrow fibrosis, according to the World Health Organization (WHO) criteria. Methods used for fibrosis evaluation: bone marrow biopsy with reticulin and collagen stains and Second harmonic generation. Fisher exact test will be used for categorical analysis. ;Overall response: anaemia, splenomegaly and constitutional symptoms, according to the IWG-MRT (International Working Group-Myeloproliferative Neoplasms Research and Treatment) and ELN (European Leukemia Net) criteria. Methods used for response evaluation: blood counts, clinical history and physical examination, and abdominal ultrasound. Fisher exact test will be used for categorical analysis. Anova test will be used for continuos variables. | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to fibrosis progression, according to the WHO criteria. Anova test will be used for continuos variables. ;Progression-free survival (PFS), according to the IWG-MRT and ELN criteria. Kaplan-Meier curve will be used for PFS evaluation.;Overall survival (OS). Kaplan-Meier curve will be used for OS evaluation.;Transfusion dependency. Anova test will be used for continuos variables. ;Reduction of inflammatory cytokines plasma levels. Anova test will be used for continuos variables. ;JAK2 pathway modulation by flow cytometry. Anova test will be used for continuos variables. | — |
Countries
Brazil
Contacts
Public ContactPaula;Sara de Melo Campos;Olalla Saad
Hemocentro de Campinas;Hemocentro de Campinas
Outcome results
None listed