TREOSULFAN for Myelofibrosis | Primary myelofibrosis | Secondary myelofibrosis

Inclusion criteria

• {"criterion_text":"- \tPatients aged between 18 and 70 years"}
• {"criterion_text":"- \tPrimary myelofibrosis or myelofibrosis secondary to essential thrombocythemia or polycythemia Vera proven by marrow biopsy"}
• {"criterion_text":"- The myelofibrosis should combine at least 2 of the following criteria: o\tconstitutional symptoms: weight loss > 10% in one year, fever (without infection), recurrent muscle, bone or join pains, extreme fatigue o\tanemia with hemoglobin < 10 gr/dL or red blood cell transfusion requirement o\tthrombocytopenia < 100 G/L o\tperipheral blast count > 1% at least found 2 times o\twhite blood cell count > 25 G/L (before a cytoreductive treatment) o\tKaryotype: +8, -7/7q-, i(17q), -5, 5q-, 12p-, inv(3), 11q23"}
• {"criterion_text":"- \tPerformance status according to ECOG at 0, 1 or 2"}
• {"criterion_text":"- \tWith health insurance coverage"}
• {"criterion_text":"- \tHaving signed a written informed consent"}
• {"criterion_text":"- \tWomen agreed to take nomegestrol acetate as contraception during and up to 6 months after treatment by treosulfan"}
• {"criterion_text":"- \tMen agreed not to conceive child during and up to 6 months after treatment by treosulfan"}

Exclusion criteria

• {"criterion_text":"- \tMyelofibrosis transformed into acute leukemia"}
• {"criterion_text":"- \tPregnant woman or breastfeeding"}
• {"criterion_text":"- \tContraindications to treosulfan o\tHypersensitivity to the active substance o\tActive non-controlled infectious disease o\tFanconi anaemia and other DNA breakage repair disorders o\tAdministration of live vaccine"}
• {"criterion_text":"- \tContraindications or any circumstance that precludes the use of the drugs involved in the protocol (especially Thiotepa and Fludarabine)"}
• {"criterion_text":"- \tPoor performance status with ECOG 3 or more"}
• {"criterion_text":"- \tCardiac failure with EF < or = 50% currently or in the past (even if corrected after treatment)"}
• {"criterion_text":"- \tRenal failure with creatininemia > 130 µmol/L or clearance < 50ml/min"}
• {"criterion_text":"- \tRespiratory function altered with vital capacity < 70% or forced expired volume < 70%"}
• {"criterion_text":"- \tBiological significant liver abnormalities; ASAT or ALAT> 2 x normal range, bilirubin > 1,5 x normal range"}
• {"criterion_text":"- \tHLA matched donor available"}
• {"criterion_text":"- \tTutorship or curatorship"}
• {"criterion_text":"- \tUnwilling or unable to comply with the protocol"}

Primary endpoints

• {"endpoint_text":"- The main criteria of judgement is disease- and rejection-free survival 12 months after HSCT.","definition_or_measurement_approach":"Disease- and rejection-free survival at 12 months after HSCT (i.e. disease-free survival and without rejection one year after haplo-identical transplantation)."}

Secondary endpoints

• {"endpoint_text":"- incidence of acute grade 2-4 and grade 3-4 GVHD according to the modified Glucksberg classification","definition_or_measurement_approach":"Incidence of acute GVHD grade 2-4 and grade 3-4 assessed at 100 days using the modified Glucksberg classification."}
• {"endpoint_text":"- incidence of chronic GVHD (limited vs extensive) at 12 months according to the revised Seattle criteria","definition_or_measurement_approach":"Incidence of chronic GVHD (limited vs extensive) at 12 months assessed according to revised Seattle criteria."}
• {"endpoint_text":"- neutrophil engraftment on day 60 post-transplantation, engraftment is defined as neutrophil count at 0.5G/L or higher for more than 3 consecutive days after transplantation, it should be confirmed by a donor chimerism","definition_or_measurement_approach":"Neutrophil engraftment by day 60 defined as neutrophil count ≥ 0.5 G/L for >3 consecutive days, confirmed by donor chimerism."}
• {"endpoint_text":"- latelet recovery: first day of platelet > 20G/L without transfusion the last 7 days assessed on day 100","definition_or_measurement_approach":"Platelet recovery assessed at day 100: first day with platelets >20 G/L without transfusion in prior 7 days."}
• {"endpoint_text":"- overall survival at 12 months","definition_or_measurement_approach":"Overall survival measured at 12 months post-transplantation."}
• {"endpoint_text":"- on-relapse mortality at 12 months","definition_or_measurement_approach":"Non-relapse mortality assessed at 12 months."}
• {"endpoint_text":"- incidence of relapse/progression at 12 months","definition_or_measurement_approach":"Incidence of relapse or progression measured at 12 months."}
• {"endpoint_text":"- incidence of rejection at 12 months","definition_or_measurement_approach":"Incidence of graft rejection assessed at 12 months."}
• {"endpoint_text":"- infection incidence at 100 days, 12 months (annexe for infection)","definition_or_measurement_approach":"Incidence of infections assessed at 100 days and at 12 months (see infection annex)."}
• {"endpoint_text":"- cytokine profile during transplantation (day-7 +/- 1 jour, J0 and day J7 +/- 1 jour )","definition_or_measurement_approach":"Cytokine profiling at specified timepoints: day -7 ±1, day 0, day +7 ±1."}
• {"endpoint_text":"- impact of genetic alterations on overall survival at 12 months and non-relapse mortality at 12 months","definition_or_measurement_approach":"Analysis of the effect of genetic alterations on overall survival and non-relapse mortality at 12 months."}

France

Earliest CTIS Part Ii Submission Date

13-06-2024

Latest Decision Or Authorization Date

23-07-2024

Processing Time Days

40

Number Of Sites

22

Number Of Participants

28

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"ESTEVE","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"MEDAC","duties_or_roles":"Monetary support; product supplier for treosulfan (named in product info)","organisation_type":""}