TASQUINIMOD for Myelofibrosis|Primary myelofibrosis|Post-polycythaemia vera myelofibrosis|Post-essential thrombocythemia myelofibrosis

Inclusion criteria

• {"criterion_text":"- 1\tDiagnosis of PMF or Post-PV MF or Post-ET MF based on a bone marrow (BM) biopsy not older than 6 months, according to the 2016 World Health Organization (appendix A)"}
• {"criterion_text":"- 10\tNegative pregnancy test at study entry for women of childbearing potential"}
• {"criterion_text":"- 11\tWomen of child-bearing potential and sexually active males must be willing and able to use highly effective methods of contraception, during treatment, and for 4 months and 6 months respectively, after study treatment (see section 9.2.3)"}
• {"criterion_text":"- 12\tPatient is capable of giving informed consent"}
• {"criterion_text":"- 13\tWritten informed consent"}
• {"criterion_text":"- 2\tRefactory or intolerant to treatment with an approved JAK inhibitor or ineligible for JAK inhibitor treatment (appendix G)"}
• {"criterion_text":"- 3\tMF classified as Intermediate-1 with disease-related symptoms (e.g. symptomatic splenomegaly), Intermediate-2 or high-risk by Dynamic International Prognostic Scoring System Plus (Passamonti et al., Blood 2010) (Appendix C)"}
• {"criterion_text":"- 4\tSpleen ≥5 cm below costal margin as measured by palpation"}
• {"criterion_text":"- 5\tAge ≥18 years"}
• {"criterion_text":"- 6\tPeripheral blood blast count of <10%"}
• {"criterion_text":"- 7\tWHO/ECOG performance status of 0,1, or 2"}
• {"criterion_text":"- 8\tAble to swallow and retain oral medication"}
• {"criterion_text":"- 9\tWilling and able to comply with scheduled visits, treatment plan and laboratory tests"}

Exclusion criteria

• {"criterion_text":"- 1\tPatients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available)"}
• {"criterion_text":"- 19\tNeed for ongoing therapy with drug substances of narrow therapeutic range that are metabolized mainly by CYP3A4 as listed in appendix H"}
• {"criterion_text":"- 20\tNeed for ongoing therapy with drug substances of narrow therapeutic range metabolized mainly by CYP1A2 as listed in appendix H"}
• {"criterion_text":"- 2\tSplenectomy"}
• {"criterion_text":"- 21\tOngoing treatment with vitamin K antagonist, unless the INR is ≤ 3.0"}
• {"criterion_text":"- 22\tPrior treatment with tasquinimod"}
• {"criterion_text":"- 23\tMajor surgery within 3 months"}
• {"criterion_text":"- 24\tPregnant or breast feeding (lactating) women"}
• {"criterion_text":"- 25\tAny other condition that would, in the Investigator’s judgment, contraindicate subject’s participation in the clinical study due to safety concerns or compliance with clinical study procedures e.g. any uncontrolled disease such as pulmonary disease, infection or seizure disorder; intestinal obstruction, inability to swallow medication, any altered mental status or psychiatric condition that would interfere with the understanding of the informed consent"}
• {"criterion_text":"- 26\tCurrent participation (during interventional treatment) in another clinical trial"}
• {"criterion_text":"- 27\tAny psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule"}
• {"criterion_text":"- 11\tImpairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of tasquinimod (e.g., ulcerative diseases, pancreatitis uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)"}
• {"criterion_text":"- 3\tSplenic irradiation within the last 6 months"}
• {"criterion_text":"- 4\tPrior allogeneic stem cell transplantation"}
• {"criterion_text":"- 5\tFollowing laboratory values within 14 days prior to registration: - Absolute Neutrophil Count (ANC) <0.5 x 109/L without G-CSF support - Platelet count <25 x 109/L without platelet transfusion - Serum creatinine >1.5 x Upper limit of normal (ULN) or GFR <30 ml/min - Serum amylase and lipase >1.5 x ULN - Alanine aminotransferase (ALT) ≥2.5 x ULN - Total bilirubin >1.5 times the upper limit of the normal range (ULN), unless elevated bilirubin is due to unconjugated hyperbilirubinemia from Gilbert’s syndrome or related to MF"}
• {"criterion_text":"- 6\tKnown active (acute or chronic) Hepatitis A, B, or C; and Hepatitis B and C carriers, HIV"}
• {"criterion_text":"- 7\tPrior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis)"}
• {"criterion_text":"- 9\tPatients with any other prior malignancies are not eligible, except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which subject has been disease-free for at least 5 years"}
• {"criterion_text":"- 10\tFailure to have fully recovered (i.e. to CTCAE Grade 1 or previous baseline) from clinically significant adverse effects of prior chemotherapy (examples of adverse effects that are not clinically significant include alopecia and lymphopenia)"}
• {"criterion_text":"- 8 Previous history of pancreatitis or risk factors for pancreatitis (eg, non-alcoholic fatty liver disease (NAFLD), history of alcohol abuse, hypertriglyceridaemia)."}
• {"criterion_text":"- 12\tEvidence of severe or currently uncontrolled cardiovascular condition (e.g. cardiac amyloidosis, pulmonary embolism, angina, hypertension, peripheral vascular disease, congestive heart failure class III or IV of the NYHA classification (appendix F), cardiac arrhythmia, acute coronary syndrome, myocardial infarction, cerebrovascular accident, major hemorrhage, intracranial hemorrhage, transient ischemic attack, or limb claudication) within 6 months prior to registration"}
• {"criterion_text":"- 13\tPatients with clinically significant bacterial, fungal, parasitic or viral infection which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/ enrollment until the course of antibiotic therapy has been completed"}
• {"criterion_text":"- 14\tAny chemotherapy, immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), anagrelide, immunosuppressive therapy, corticosteroids >10 mg/day prednisone or equivalent, or growth factor treatment (eg, erythropoietin), or hormones (eg, androgens, danazol) within 2 weeks prior to initiation of tasquinimod. The only chemotherapy allowed will be hydroxyurea which has to be stopped within 1 day prior to initiation of tasquinimod"}
• {"criterion_text":"- 15\tTreatment with fedratinib within 7 days, or momelotinib within 2 days prior to initiation of tasquinimod. For ruxolitinib no wash-out period is required before start of tasquinimod"}
• {"criterion_text":"- 16\tAny investigational treatment for MF within 2 weeks or 5 half-lives whichever is shorter"}
• {"criterion_text":"- 17\tHistory of severe hypersensitivity reaction to any component of tasquinimod"}
• {"criterion_text":"- 18\tSystemic treatment within 14 days prior to the initiation of tasquinimod with any of the moderate or strong inhibitor, or moderate or strong inducer of cytochrome P-3A4 (CYP3A4) listed in appendix H"}

Primary endpoints

• {"endpoint_text":"- Phase 1b: Dose limiting toxicity (DLT), as defined in section 7.1 and recommended phase 2 dose level (RP2D), as defined in section 7.2","definition_or_measurement_approach":"DLT as defined in protocol section 7.1; RP2D determined per protocol section 7.2 (dose-limiting toxicity and recommended phase 2 dose level assessments as specified in protocol)."}
• {"endpoint_text":"- Phase 2: Proportion of participants with at least 35% reduction in spleen volume from baseline at Week 32 (SVR35W32) as measured by magnetic resonance imaging (MRI), per International Working Group (IWG) criteria, based on MRI review","definition_or_measurement_approach":"Spleen volume reduction measured by MRI at Week 32, assessed per International Working Group (IWG) criteria and based on MRI review (SVR ≥35% at Week 32)."}

Secondary endpoints

• {"endpoint_text":"- Proportion of participants with at least 50% reduction in palpable splenomegaly from baseline per IWG criteria","definition_or_measurement_approach":"Palpable spleen size assessed and proportion achieving ≥50% reduction from baseline per IWG criteria (by palpation)."}
• {"endpoint_text":"- Proportion of patients with at least 35% reduction in spleen volume from baseline (SVR35) as measured by MRI, per IWG criteria, based on MRI review","definition_or_measurement_approach":"MRI-assessed spleen volume reduction (SVR ≥35%) per IWG criteria based on MRI review."}
• {"endpoint_text":"- Overall survival, as defined from date of registration until date of death from any cause. Participants still alive at the date last contact, will be censored","definition_or_measurement_approach":"Time from registration to death from any cause; censoring at last contact for survivors."}
• {"endpoint_text":"- Safety, as assessed by clinical, laboratory, and vital sign events; graded by the NCI CTCAE v5","definition_or_measurement_approach":"Adverse events and safety assessments graded using NCI CTCAE v5, including clinical, laboratory and vital sign evaluations."}
• {"endpoint_text":"- Proportion of participants with at least 50% reduction in total symptom score (TSS) after 32 weeks from baseline as measured by MPN-SAF TSS","definition_or_measurement_approach":"MPN-SAF TSS questionnaire used to measure symptoms; proportion achieving ≥50% reduction from baseline at 32 weeks."}
• {"endpoint_text":"- Reduction in grade of bone marrow fibrosis from baseline as measured by the European consensus grading system","definition_or_measurement_approach":"Bone marrow fibrosis grade assessed using the European consensus grading system; reduction from baseline recorded."}
• {"endpoint_text":"- Anemia response per IWG criteria","definition_or_measurement_approach":"Anemia response defined and assessed per International Working Group (IWG) criteria."}
• {"endpoint_text":"- Red blood cell (RBC) transfusion (number of packed cells) during tasquinimod treatment","definition_or_measurement_approach":"Number of packed red blood cell units transfused during tasquinimod treatment."}
• {"endpoint_text":"- The effect of tasquinimod on the allelic burden of the driver mutations","definition_or_measurement_approach":"Change in variant allele frequency (VAF) of driver mutations (JAK2, CaLR, MPL) measured per protocol-specified molecular assays."}

Netherlands

Earliest CTIS Part Ii Submission Date

16-10-2024

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

559

Number Of Sites

5

Number Of Participants

21

Germany

Earliest CTIS Part Ii Submission Date

16-10-2024

Latest Decision Or Authorization Date

29-04-2026

Processing Time Days

560

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"Sweden","full_name":"Scantox Sweden AB","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Stichting Amsterdam UMC","duties_or_roles":"Pathology and Imaging review","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Denmark","full_name":"Klifo A/S","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Hospital/Clinic/Other health care facility"}