Tasquinimod in Patients with Myelofibrosis Refractory to or Intolerant for JAK2 Inhibition

NCT06605586 | Recruiting Phase 1 DMC

• 2 other identifiers: HO1722024-511565-11-00
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 6

Brief Summary

The goal of this clinical trial is to learn if therapy can be improved in patients with myelofibrosis (MF) who have primary resistance or who have progressed after treatment with a Janus kinase (JAK) inhibitor or are intolerant for this category of drugs. The main questions it aims to answer are:

• To evaluate the feasibility and safety of once daily dose of tasquinimod for 24 weeks (6 cycles)
• To determine the optimal dose Patients will be treated once daily with tasquinimod for a maximum period of 24 weeks (6 cycles). During the study most (diagnostic) procedures are part of the standard of care. Different from standard of care:
• Participation may lead to extra visits to the outpatient clinic
• Additional blood will be drawn when blood is already taken per standard of care
• Bone marrow sampling at entry and at the end of the trial
• MRI scans (or CT-scans) have to be performed
• Quality-of-life questionnaires have to be filled out

Conditions

Myelofibrosis

Outcome Measures

Primary Outcomes (2)

• SVR35W24

  Proportion of patients with at least 35% reduction in spleen volume from baseline at Week 24 (SVR35W24) as measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan, per International Working Group (IWG) criteria, based on MRI review.

  24 weeks after start treatment

• DLT phase I

  To determine the dose limiting toxicity (DLT) of tasquinimod. Pre-defined adverse events (AEs) that occur within 28 days of the start of study treatment will be considered a DLT, unless the AE is definitely unrelated to tasquinimod.

  From enrollment until 28 days after start treatment

Secondary Outcomes (9)

• RBC transfusions

  Until end of protocol treatment after 24 weeks

• Changes in variant allele frequency

  Until end of protocol treatment after 24 weeks

• Change in splenomegaly

  Until end of protocol treatment after 24 weeks

• Change in spleen volume by MRI review

  Until end of protocol treatment after 24 weeks

• Changes of total symptom score

  Until end of protocol treatment after 24 weeks

Other Outcomes (1)

• Plasma concentrations

  Until end of protocol treatment after 24 weeks

Study Arms (1)

Tasquinimod

EXPERIMENTAL

Patients will be treated with tasquinimod capsules 0.5 mg/day for 14 days (half cycle) and then capsules of 1 mg/day for the remaining 14 days in the first cycle. In consecutive 28-day cycles 1 mg/day (or if 1 mg/day is not tolerated, reduction to 0.75 or 0.5 mg/day is allowed, followed by dose re-escalation whenever possible). Patients will be treated for a maximum period of 24 weeks (6 cycles).

Drug: Tasquinimod

Interventions

Tasquinimod DRUG

treatment with tasquinimod capsules once daily

Tasquinimod

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Stichting Hemato-Oncologie voor Volwassenen Nederland: lead

Study Sites (6)

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

Related Links

• HOVON website

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

tasquinimod

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Peter te Boekhorst, Dr.

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter te Boekhorst, Dr.

CONTACT

0031107041560; hovon@erasmusmc.nl

Martina Chrysandt, Dr.

CONTACT

0031107041560; hovon@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2024
• First Posted: September 20, 2024
• Study Start: February 20, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): March 1, 2030
• Last Updated: March 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

DE (1); NL (5)