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Sindromi MIELOPROLIFERATIVE CRONICHE target: leucemia mieloide cronica
Trattamento: Nilotinib + asciminib
Criteri inclusione:
1) Diagnosis of CP-CML according to the WHO and no previous history of progression to AP/BP CML.2) First-line treatment with nilotinib for at least 3 calendar years, followed by first TFR attempt.3) Failed first TFR attempt followed by at least 1 year of nilotinib retreatment before enrollment in TFR2 stage.4) MR4 or better (BCR-ABL ≤ 0.01% IS) assessed at screening.5) Patient must meet the following laboratorya. Absolute neutrophil count ≥1.0 x 109/Lb. Platelets ≥75 x 109/Lc. Hemoglobin (Hgb) ≥ 9 g/dLd. Serum creatinine < 1.5 mg/dLe. Total bilirubin ≤ 2 x ULN except for patients with Gilbert’s syndrome who may only be included if total bilirubin ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULNf. AST and ALT ≤ 3.0 x ULNg. ALP ≤ 2.5 x ULNh. Serum lipase ≤ 1.5 x ULN.j. Serum levels of potassium, magnesium, total calcium within the normal limits. Correction of electrolytes levels with supplements to fulfil enrolment criteria is allowed.
Criteri esclusione:
1) Patients with known atypical transcript.2) CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past).3) Dose reductions/interruptions due to neutropenia or thrombocytopenia in the past 6 months4) History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis5) Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to study entry.
1) Patients with CP-CML, treated with TKI monotherapy or TKI in association with other drugs (such as interferon, BCR-ABL1 peptidic vaccine and others)2) Treatment with TKI discontinued for any reason3) Deep Molecular Response (DMR), defined as MR4, or MR4.5, or MR5 confirmed at least three times before TKI discontinuation In patients who discontinued TKIs before the establishment of molecular standardization, DMR will be defined as a level of BCR-ABL1 transcript undetectable by qPCR or by qualitative PCR, confirmed in at least two controls
Patients who were diagnosed with accelerated or blastic phase CML will be excluded
Leggi tutto: AO Ordine Mauriziano di Torino - Sindromi mieloprofliferative
A Phase 3, Randomized, Double-blind, Active-Comparator-Controlled Clinical Study to Evaluate the Efficacy and Safety of Bomedemstat (MK-3543) versus Hydroxyurea in Cytoreductive Therapy Naïve Essential Thrombocythemia Participants
Contatti: Monia Marchetti, Questo indirizzo email è protetto dagli spambots. È necessario abilitare JavaScript per vederlo.
Trattamento: Bomedemstat
Sindromi MIELOPROLIFERATIVE CRONICHE target: Essential Thrombocythemia
Principali Criteri Inclusione:
1. Based on the WHO diagnostic criteria for myeloproliferative neoplasms has a diagnosis of ET and an indication for cytoreductive therapy regardless of age or risk status. Indications for cytoreductive therapy include but are not limited to:
• High-risk patients (history of thrombosis at any age; or age >60 years with JAK2 V617F mutation),
• Acquired VWD and/or disease-related major bleeding,
• Splenomegaly (defined as a spleen volume greater than 450 mm3),
• Progressive thrombocytosis and/or leukocytosis,
• Disease-related symptoms (eg, pruritis, fatigue, night sweats), and
• Vasomotor/microvascular disturbances not responsive to ASA (eg, erythromelalgia, headaches/chest pain).
2. Has a bone marrow fibrosis score of Grade 0 or Grade 1, as per a modified version of the European Consensus Criteria for Grading Myelofibrosis (Appendix 10).
3. Has received no prior cytoreductive treatment for their ET.
4. Has a platelet count of >450 × 109/L (450k/μL) assessed up to 72 hours before first dose of study intervention.
5. Has an ANC ≥0.75 × 109/L assessed up to 72 hours before first dose of study intervention.
6. Has a life expectancy of >52 weeks in the opinion of the investigator.
13. Has an ECOG Performance Status of 0 to 2 assessed within 7 days before the start of study intervention
Principali Criteri Esclusione:
3. Evidence at the time of Screening of increased risk of bleeding, including any of the following:
- History of severe thrombocytopenia or platelet dysfunction unrelated to a myeloproliferative disorder or its treatment.
- Known hereditary bleeding disorder (eg, dysfibrinogenemia, factor IX deficiency, hemophilia, VWD, disseminated intravascular coagulation, fibrinogen deficiency, or other clotting factor deficiency).
- Active or chronic bleeding within 8 weeks before randomization.
- An autoimmune disorder causing bleeding.
4. History of a malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
Contatti: Monia MarchettiQuesto indirizzo email è protetto dagli spambots. È necessario abilitare JavaScript per vederlo.
SCDU Ematologia, AOU SS Antonio e Biagio e Cesare Arrigo - Alessandria
Sindromi MIELOPROLIFERATIVE CRONICHE target: TROMBOCITEMIA ESSENZIALE
Studio di fase 3
1. Has a diagnosis of ET per WHO 2016 diagnostic criteria for myeloproliferative neoplasms (Appendix 9).
2. Has a bone marrow fibrosis score of Grade 0 or Grade 1, as per a modified version of the European Consensus Criteria for Grading Myelofibrosis (Appendix 11)
3. Has a history of inadequate response to or intolerance of hydroxyurea per at least 1 of the following criteria, based on modified ELN criteria for hydroxyurea resistance or intolerance [Barosi, G., et al 2007]
Hydroxyurea Resistance (or Inadequate Response):
- Platelet count >600 × 109/L after 3 months of at least 2 g/day or MTD of hydroxyurea, or
- Platelet count >400 × 109/L and WBC <2.5 ×109/L at any dose and duration of hydroxyurea, or
- Platelet count >500 × 109/L and Hb <10 g/dL at any dose and duration of hydroxyurea, or
- Platelet count >450 × 109/L at any dose and duration of hydroxyurea if the above criteria are not met.
• Hydroxyurea Intolerance:
- ANC <1 × 109/L, or platelet count <150 × 109/L, or Hb <10 g/dL at the lowest dose of hydroxyurea to achieve a hematologic remission, defined as platelet count ≤400 × 109/L and WBC <10 × 109/L
- Unacceptable hydroxyurea-related non-hematologic toxicities (eg, pulmonary toxicities such as pneumonitis, fibrosis and allergic alveolitis; hepatotoxicity; hemolytic anemia; vasculitic toxicities; mucocutaneous manifestations; precancerous or cancerous skin lesions; gastrointestinal symptoms; or fever) at a dose of hydroxyurea needed to achieve CHR defined as:
◦ Toxicity that recurred after rechallenge with hydroxyurea
◦ Toxicity requiring permanent discontinuation of hydroxyurea
◦ Toxicity with intensity of Grade 4 (CTCAE v5.0) lasting >1 week
◦ Toxicity with intensity of Grade 3 (CTCAE v5.0) lasting >2 weeks
4. Has an inadequate or loss of response to their most recent prior ET therapy, requiring a change of cytoreductive therapy, as demonstrated by one of the following [National Comprehensive Cancer Network 2022]:
• Intolerance or inadequate response to hydroxyurea, formulations of interferon alfa, or anagrelide
• New thrombosis or disease-related major bleeding (eg, acquired Von Willebrand’s disorder)
• Progressive thrombocytosis (platelet count >600 × 109/L)
• Progressive leukocytosis (WBC >11 × 109/L)
• Uncontrolled disease-related symptoms (for study purposes this has been defined as a single symptom score of MFSAF v4.0 ≥4)
• Vasomotor/microvascular disturbances not responsive to aspirin (eg, headaches, chest pain or erythromelalgia)
5. Has a platelet count > 450 × 109/L (450k /μL) assessed up to 72 hours before first dose of study intervention
6. Has an ANC ≥0.75 × 109/L assessed up to 72 hours before first dose of study intervention
7. Has a life expectancy of >52 weeks
8. Participants may have received up to 3 prior lines of therapy including hydroxyurea.
15. Has an ECOG Performance Status of 0 to 1 assessed within 7 days before the start of study intervention.
Leggi tutto: AOU SS Antonio e Biagio e Cesare Arrigo di Alessandria - Sindromi mieloprofliferative
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