Tasquinimod treatment for patients with myelofibrosis who can't tolerate JAK inhibitors

A Phase 1b/2 Trial with Tasquinimod in Patients with Myelofibrosis (primary, Post-PV or PostET) Refractory to or Intolerant for JAK2 Inhibition: the TasqForce Trial

This study is testing if tasquinimod can be a safe and effective treatment for people with myelofibrosis who can't tolerate JAK inhibitors.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Stichting Hemato-Oncologie voor Volwassenen Nederland (Academic / other)
• Drugs / interventions: fedratinib, momelotinib, ruxolitinib, chemotherapy, prednisone
• Locations: 6 sites (Aachen and 5 other locations)
• Trial ID: NCT06605586 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and feasibility of tasquinimod, administered once daily for 24 weeks, in patients with myelofibrosis who are refractory to or intolerant of JAK inhibitors. The study will assess the optimal dosage of tasquinimod while incorporating standard diagnostic procedures, including bone marrow sampling and imaging scans. Participants will also complete quality-of-life questionnaires to gauge the treatment's impact. The trial seeks to provide a new therapeutic option for patients with limited treatment alternatives.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with myelofibrosis who are refractory to or intolerant of JAK inhibitors.

Not a fit: Patients with myelofibrosis who have not been treated with JAK inhibitors or those with low-risk disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new option for patients with myelofibrosis who have not responded to existing therapies.

How similar studies have performed: While there have been studies on JAK inhibitors for myelofibrosis, the use of tasquinimod in this context is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Diagnosis 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.
* Refactory or intolerant to treatment with an approved JAK inhibitor or ineligible for JAK inhibitor treatment.
* MF classified as Intermediate-1 with disease-related symptoms (e.g. symptomatic splenomegaly), Intermediate-2 or high-risk by Dynamic International Prognostic Scoring System Plus
* Spleen ≥5 cm below costal margin as measured by palpation.
* Age ≥18 years.
* Peripheral blood blast count of \<10%.
* WHO/ECOG performance status of 0, 1, or 2.
* Able to swallow and retain oral medication.
* Willing and able to comply with scheduled visits, treatment plan and laboratory tests.
* Negative pregnancy test at study entry for women of childbearing potential. Women 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.
* Patient is capable of giving informed consent.
* Written informed consent.

Exclusion Criteria:

* Patients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
* Splenectomy.
* Splenic irradiation within the last 6 months.
* Prior allogeneic stem cell transplantation.
* Following 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
* Known active (acute or chronic) Hepatitis A, B, or C; and Hepatitis B and C carriers, HIV.
* Prior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis).
* Patients 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.
* Failure 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).
* Impairment 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).
* Evidence 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.
* Patients 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.
* Any 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; erythropoetin use within 28 days 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.
* Treatment 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.
* Any investigational treatment for MF within 2 weeks or 5 half-lives whichever is shorter.
* History of severe hypersensitivity reaction to any component of tasquinimod.
* Systemic 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)
* Need for ongoing therapy with drug substances of narrow therapeutic range that are metabolized mainly by CYP3A4
* Need for ongoing therapy with drug substances of narrow therapeutic range metabolized mainly by CYP1A2
* Ongoing treatment with vitamin K antagonist, unless the INR is ≤ 3.0
* Prior treatment with tasquinimod.
* Major surgery within 3 months.
* Pregnant or breast feeding (lactating) women.
* Any 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
* Current participation (during interventional treatment) in another clinical trial.
* Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Where this trial is running

Aachen and 5 other locations

• DE-Aachen-UKAACHEN — Aachen, Germany (Not_yet_recruiting)
• NL-Amsterdam-AmsterdamUMC — Amsterdam, Netherlands (Not_yet_recruiting)
• NL-Groningen-UMCG — Groningen, Netherlands (Not_yet_recruiting)
• NL-Nijmegen-RADBOUDUMC — Nijmegen, Netherlands (Recruiting)
• NL-Rotterdam-ERASMUSMC — Rotterdam, Netherlands (Not_yet_recruiting)
• NL-Utrecht-UMCUTRECHT — Utrecht, Netherlands (Not_yet_recruiting)

Study contacts

• Principal investigator: Peter te Boekhorst, Dr. — Erasmus Medical Center
• Study coordinator: Peter te Boekhorst, Dr.

Conditions Myelofibrosis