AO Ordine Mauriziano di Torino - Sindromi mieloprofliferative

CAMN107AIT15 -DANTE: A phase II, single-arm, multicenter study of full treatment-free remission in patient with chronic myeloid leukemia in chronic phase treated with nilotinib in first-line therapy who have archived a sustained deep molecular response for at leats 1 year

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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 laboratory
a. Absolute neutrophil count ≥1.0 x 109/L
b. Platelets ≥75 x 109/L
c. Hemoglobin (Hgb) ≥ 9 g/dL
d. Serum creatinine < 1.5 mg/dL
e. 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 ULN
f. AST and ALT ≤ 3.0 x ULN
g. ALP ≤ 2.5 x ULN
h. 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 months
4) History of acute pancreatitis within 1 year prior to study entry or past medical history of chronic pancreatitis
5) 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.

ITALY-TFR: Studio osservazionale in pazienti adulti con leucemia mieloide cronica (LMC) che hanno discontinuato inibitori di tirosin-kinasi (TKI) in Italia

Sindromi MIELOPROLIFERATIVE CRONICHE target: leucemia mieloide cronica

Criteri inclusione:

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 reason
3) 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

Criteri esclusione:

Patients who were diagnosed with accelerated or blastic phase CML will be excluded

REGISTRO LMC: Studio osservazionale multicentrico retrospettivo e prospettico su pazienti affetti da leucemia mieloide cronica: raccolta di dati epidemiologici e clinici nella pratica clinica reale

Sindromi MIELOPROLIFERATIVE CRONICHE target: leucemia mieloide cronica

Criteri inclusione:Pazienti con LMC Ph+ in qualsiasi fase della malattia

Criteri esclusione: nessuno

Mfactor: Studio osservazionale multicentrico retrospettivo e prospettico sui pazienti affetti da Mielofibrosi. Analisi per la comprensione del ruolo di infiammazione e disimmunità nell’ambito di genesi, progressione della malattia e sue complicanze

Criteri inclusione: Pazienti con diagnosi di Mielofibrosi primaria secondo i criteri WHO

Criteri esclusione: nessuno

XPORT-MF-034: A Phase 1/3 study to evaluate efficacy and safety of Selinexor in combination with Ruxolitinib in treatment-naïve patients with myelofibrosis

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Sindromi MIELOPROLIFERATIVE CRONICHE target: Mielofibrosi

Trattamento: ruxolitinib+selinexor vs ruxolitinib+pacebo

Criteri inclusione:

1) A diagnosis of primary MF, post-essential thrombocythemia (ET), or postpolycythemia vera (PV) MF according to the 2016 World Health Organization (WHO) classification of MPN, confirmed by the most recent local pathology report
2) Measurable splenomegaly during the screening period as demonstrated by spleen volume of ≥450 cm3 by MRI or CT scan
3) Patients with DIPSS risk category of intermediate-1, or intermediate-2, or high-risk
4) Platelet count ≥100 × 109/L without platelet transfusion
5) Absolute neutrophil count (ANC) ≥1.0 × 109/L
6) Active symptoms of MF as determined by presence of at least 2 symptoms with a score ≥3 or total score of ≥10 at screening using the MFSAF v4.0.
7) Patient currently not eligible for stem cell transplantation

Criteri esclusione:

1) More than 10% blasts in peripheral blood or bone marrow
2) Previous treatment with JAK inhibitors for MF

XPORT-MF-044: A phase 2 study to evaluate the efficacy and safety of Selinexor monotherapy in subjects with JAK inhibitor-naïve myelofibrosis and moderate thrombocytopenia

Sindromi MIELOPROLIFERATIVE CRONICHE target: myelofibrosis and moderate thrombocytopenia

Trattamento: Selinexor 60mg vs selinexor 40 mg

Criteri inclusione:

1) A diagnosis of primary MF, post-essential thrombocythemia (ET), or postpolycythemia vera (PV) MF according to the 2016 World Health Organization (WHO) classification of MPN confirmed by the most recent local pathology report
2) Measurable splenomegaly during the screening period as demonstrated by spleen volume of ≥450 cm3 by MRI or CT scan
3) Patients with DIPSS risk category of intermediate-1, or intermediate-2, or high-risk
4) Platelet count of 50 to <100 x 109 /L without platelet transfusion within 7 days prior to the first dose of selinexor
5) Absolute neutrophil count (ANC) ≥1.0 × 109/L
6) Active symptoms of MF as determined by presence of at least 2 symptoms with a score ≥3 or total score of ≥10 at screening using the MFSAF v4.0.
7) Patient currently not eligible for stem cell transplantation

Criteri esclusione:

1) More than 10% blasts in peripheral blood or bone marrow
2) Previous treatment with JAK inhibitors for MF

MK3543-006: A Phase v3, randomized, active-comparator-Controlled Clinical Study to Evaluate the Safety and Efficacy fo Bomedemstat (MK-3543/IMG-7289) versus Best Available Therapy (BAT) in participants with Essential Thrombocytemia who have An inadequate response to or are intollerant of hydroxyurea

Sindromi MIELOPROLIFERATIVE CRONICHE target: Trombocitemia essenziale

Trattamento: Bomedemstat vs BAT (anagrelide o interferone)

Criteri inclusione:

1) Has a diagnosis of ET per WHO 2016 diagnostic criteria for myeloproliferative neoplasms
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
3) Has a history of inadequate response to or intolerance of hydroxyurea per at least 1 of the following criteria:
• 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:
• 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) Participants may have received up to 3 prior lines of therapy including hydroxyurea.
8) Has an ECOG Performance Status of 0 to 1

Criteri esclusione:

1) Evidence at the time of Screening of increased risk of bleeding
2) Use of prohibited medication within 14 days of first dose of study intervention (eg, all hematopoietic growth factors, MAOIs, strong inhibitors and inducers of CYP3A4 or CYP2D6, drugs such as chloroquine whose metabolites are known to inhibit CYP3A4 or CYP2D6, Class 1c antiarrhythmics such as propafenone that are known to cause thrombocytopenias, etc) or expected to require any of these medications during study treatment