Tasquinimod for Myelofibrosis

Overseen By Lucia Masarova, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: Ruxolitinib

Must not be taking: Corticosteroids, Chemotherapy, Immunosuppressives, others

Disqualifiers: Cardiac disease, Hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 6 cycles (approximately 6 months)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether tasquinimod, alone or with ruxolitinib (a medication for myelofibrosis), can help manage various types of myelofibrosis, a bone marrow disorder that disrupts blood cell production. Participants are divided into two groups: one receives only tasquinimod, while the other continues ruxolitinib treatment along with tasquinimod. Suitable candidates have myelofibrosis requiring treatment and have not responded well to ruxolitinib after at least three months, or they have low blood cell counts. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in myelofibrosis treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting the study. You must stop any chemotherapy, immunomodulatory drugs, platelet-reducing therapy, and immunosuppressive therapy at least 28 days before the study. Some medications like hydroxyurea can be continued until one day before starting the trial, and ruxolitinib can be continued if you are in the combination cohort.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tasquinimod is generally well tolerated, meaning most people can handle it without serious issues. Early studies suggested it is safe, with manageable side effects. However, complete details on side effects in humans are not yet available.

Regarding the combination of tasquinimod with ruxolitinib, limited information exists about its safety. This trial is in the early stages of human testing, so while initial signs are promising, more evidence is needed to understand how well people can tolerate the combination.

Ruxolitinib has already received FDA approval for other uses, indicating its safety is well understood when used alone. However, since researchers are still studying its combination with tasquinimod, the full safety profile of the combination remains unknown. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about tasquinimod for myelofibrosis because it brings a fresh approach to managing this challenging condition. Unlike standard treatments like ruxolitinib, which primarily target Janus kinase (JAK) pathways, tasquinimod works differently by inhibiting the S100A9 protein, potentially reducing inflammation and fibrosis in the bone marrow. This novel mechanism of action offers hope for patients who have not responded well to existing therapies or who experience low blood counts. By adding tasquinimod to the treatment arsenal, there's potential for improved outcomes and a new way to tackle the disease's progression.

What evidence suggests that this trial's treatments could be effective for myelofibrosis?

Research has shown that tasquinimod may help treat myelofibrosis, a type of bone marrow cancer. Studies have found that tasquinimod can reduce abnormal cell growth, an enlarged spleen, and scarring in the bone marrow in experimental models. This suggests it might help manage symptoms in people with various forms of myelofibrosis. In this trial, participants taking ruxolitinib without sufficient improvement will be assigned to different groups. Group 1 will receive tasquinimod alone, while Group 2 will receive tasquinimod alongside their continued ruxolitinib dose. Early findings suggest these approaches might be safe and effective for those who do not respond well to other treatments. ^{3 4 6 7 8}

Who Is on the Research Team?

Lucia Masarova, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with certain types of bone marrow disorders: Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF). Specific eligibility criteria are not provided, but typically include factors like age, disease stage, and overall health.

Inclusion Criteria

For women of childbearing potential, a documented negative serum or urine pregnancy test within 14 days prior to the administration of study drug.

Participants must provide written informed consent.

Willing and able to comply with scheduled visits, treatment plan and laboratory tests.

Exclusion Criteria

Known hypersensitivity to tasquinimod or any excipients in the study treatments

I have had pancreatitis before.

Prior inclusion in this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tasquinimod alone or in combination with ruxolitinib in 28-day cycles

6 cycles (approximately 6 months)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for adverse events and response duration

Up to 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib
• Tasquinimod

Trial Overview The study is testing the effectiveness of a drug called Tasquinimod alone or combined with another medication named Ruxolitinib in controlling PMF, post-PV MF, or post-ET MF. It's an open-label phase 2 study which means everyone knows what treatment they're getting.

How Is the Trial Designed?

Group I: Group 2 Experimental Treatment 2 Interventions

Participants who are already on a stable dose of ruxolitinib for at least 8 weeks who have achieved a sub-optimal response will be assigned to Group 2. In Group 2, participants will receive tasquinimod daily on days 1-28 and ruxolitinib dose will be continued.

Group II: Group 1 Experimental Treatment 1 Intervention

Participants have already been receiving ruxolitinib for at least 3 months and are not responding well to ruxolitinib or have low blood cell counts, participants will be assigned to Group 1. In Group 1, participants will receive tasquinimod alone daily each 28 day cycle.

Ruxolitinib is already approved in United States, European Union for the following indications:

Approved in United States as Jakafi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Approved in European Union as Jakavi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Active Biotech AB

Industry Sponsor

Trials

12

Recruited

2,200+

Published Research Related to This Trial

Ruxolitinib has significantly changed the treatment approach for myelofibrosis (MF), but many hematologists in Italy do not use advanced genetic scoring systems for prognosis due to limited access to next-generation sequencing.

Key management practices for ruxolitinib include assessing infection risk before treatment, establishing clinical triggers for therapy regardless of risk category, and implementing a monitoring schedule during the first 12 weeks, highlighting the need for standardized international guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tracing the decision-making process for myelofibrosis: diagnosis, stratification, and management of ruxolitinib therapy in real-word practice. Breccia, M., Baratè, C., Benevolo, G., et al.[2023]

Ruxolitinib is a dual inhibitor of JAK1 and JAK2, which are crucial in the development of myelofibrosis (MF), and it has been FDA-approved since November 2011 for treating intermediate or high-risk MF.

The review discusses Ruxolitinib's current role in managing MF and explores its potential future applications in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. Malhotra, H.[2021]

Ruxolitinib (RUX) is an effective treatment for myelofibrosis (MF), particularly in patients with less advanced disease, as it helps reduce splenomegaly and inflammatory symptoms.

However, about 40% of patients may not respond well to RUX or may experience intolerable side effects, leading to discontinuation; a careful strategy for stopping RUX, possibly with steroids, can help mitigate withdrawal symptoms known as Ruxolitinib Discontinuation Syndrome (RDS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Light and shade of ruxolitinib: positive role of early treatment with ruxolitinib and ruxolitinib withdrawal syndrome in patients with myelofibrosis. Baek, DW., Cho, HJ., Lee, JM., et al.[2022]

Ruxolitinib is the first FDA-approved JAK inhibitor for myelofibrosis (MF), providing significant palliative benefits such as reducing spleen size and improving symptoms for many patients, based on the COMFORT I and II studies.

Ruxolitinib is the only treatment shown to improve survival in MF patients, although it is not a cure, highlighting its importance in managing this complex disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clarifying the use of ruxolitinib in patients with myelofibrosis. Kremyanskaya, M., Atallah, EL., Hoffman, R., et al.[2021]

In a study of 56 myelofibrosis patients treated with ruxolitinib, the presence of multiple gene mutations, particularly high-risk mutations, was associated with shorter treatment duration and progression-free survival, indicating a reduced efficacy of the drug.

Ruxolitinib was less effective in reducing spleen size and improving symptoms in patients with specific mutations (ASXL1, EZH2, SRSF2), highlighting the importance of genetic profiling in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of the effect of gene mutations on the efficacy of ruxolitinib in patients with myelofibrosis based on second-generation sequencing technology]. Tan, YX., Luo, J., Huang, JX., et al.[2023]

In a study of 408 patients with Myelofibrosis treated with ruxolitinib, 34.9% achieved a spleen response at 6 months, with factors like high risk scores and large spleen size negatively impacting response rates.

Patients receiving higher doses of ruxolitinib (≥10 mg BID) in the first 12 weeks had better response rates, suggesting that early treatment and appropriate dosing can improve therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline factors associated with response to ruxolitinib: an independent study on 408 patients with myelofibrosis. Palandri, F., Palumbo, GA., Bonifacio, M., et al.[2019]

In a phase 2 study involving 45 patients with myelofibrosis, a dose-escalation strategy for ruxolitinib starting at 10 mg twice daily helped reduce spleen size by an average of 17.3% and improved symptom severity by 45.6% after 24 weeks.

This approach also resulted in fewer severe hematological side effects, with only 20% of patients experiencing grade 3/4 anemia, suggesting that careful dose management can maintain treatment efficacy while minimizing adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of an alternative ruxolitinib dosing regimen in patients with myelofibrosis: an open-label phase 2 study. Talpaz, M., Erickson-Viitanen, S., Hou, K., et al.[2021]

In a study of 889 patients with myelofibrosis, factors such as low platelet count, low hemoglobin, primary myelofibrosis, lack of spleen response at 3 months, and a low starting dose of ruxolitinib were linked to a higher risk of discontinuing treatment early or dying within 5 years.

A new prognostic model (STR-PM) was developed to categorize patients into low, intermediate, and high-risk groups for early treatment failure, helping to identify those who may benefit from alternative therapies instead of ruxolitinib monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Prognostic Model to Predict Ruxolitinib Discontinuation and Death in Patients with Myelofibrosis. Palandri, F., Palumbo, GA., Bonifacio, M., et al.[2023]

Ruxolitinib is an effective treatment for intermediate or high-risk myelofibrosis, significantly reducing spleen size and alleviating related symptoms, which improves patients' quality of life.

While ruxolitinib can cause dose-dependent anemia and thrombocytopenia, these side effects can be managed with dose adjustments and monitoring, allowing most patients to continue treatment without permanent discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosing. Mesa, RA., Cortes, J.[2021]

In a study of 219 patients with myelofibrosis, ruxolitinib significantly improved health-related quality of life (HRQoL) and reduced disease-related symptoms over 48 weeks compared to best available therapy (BAT).

Ruxolitinib treatment led to notable enhancements in physical functioning, fatigue, and appetite, with significant improvements observed as early as week 8 and continuing throughout the study, supporting its efficacy as a treatment for symptomatic myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life and symptoms in patients with myelofibrosis treated with ruxolitinib versus best available therapy. Harrison, CN., Mesa, RA., Kiladjian, JJ., et al.[2021]

In a study of 462 patients with myelofibrosis, the safety profile of ruxolitinib was found to be comparable between new and prevalent users, with common adverse drug reactions including thrombocytopenia and anaemia.

Patients who switched to ruxolitinib experienced higher rates of bleeding events and serious infections, while the incidence of second primary malignancies was notably higher in those who were already using ruxolitinib, supporting its long-term use despite these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world non-interventional long-term post-authorisation safety study of ruxolitinib in myelofibrosis. Barraco, F., Greil, R., Herbrecht, R., et al.[2021]

Citations

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Results from tasquinimod study in heavily pretreated ... The results highlight the potential for targeting the tumor microenvironment with tasquinimod to augment the efficacy of other myeloma therapies ...

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Preclinical efficacy of tasquinimod-based combinations in ... We first determined the expression of S100A8 and S100A9 messenger RNA (mRNA) in 173 patients for whom RNA-seq data were available in The Cancer Genome Atlas AML ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06605586

Tasquinimod in Patients with Myelofibrosis Refractory to or ... 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 ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3142/533769/Evaluation-of-the-Lethal-Activity-and-Its

Evaluation of the Lethal Activity and Its Mechanism of ... Notably, TQ was shown to reduce myeloproliferation, splenomegaly and bone marrow fibrosis in JAK2-V617F mice. In the present studies, we ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06327100

Open Label Phase 2 Study of Tasquinimod in Patients With ... Primary Objectives To determine anti-tumor activity of tasquinimod in patients with PMF, post-PV MF, and post-ET MF in a monotherapy and in combination with ...

6. activebiotech.com activebiotech.com/en/projects/tasquinimod/

Tasquinimod Tasquinimod in myelofibrosis. Preclinical studies have shown ... tasquinimod and the safety read-out showed that tasquinimod was generally well tolerated.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06327100?term=AREA%5BConditionSearch%5D(Essential%20thrombocythemia%20OR%20%22essential%20thrombocytemia%22%20OR%20%22%20essential%20thrombocythaemia%22%20OR%20%22%20essential%20thrombocytosis%22%20OR%20%22%20hemorrhagic%20thrombocythemia%22%20OR%20%22%20primary%20thrombocythemia%22%20OR%20%22%20primary%20thrombocytosis%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=9

Study Details | NCT06327100 | Open Label Phase 2 ... Because no dosing or adverse event data are currently available on the use of tasquinimod as monotherapy or in combination with ruxolitinib in patients <18 ...

8. activebiotech.com activebiotech.com/en/mfn_news/active-biotechs-clinical-trial-of-tasquinimod-in-myelofibrosis-approved-in-europe/

Active Biotech's clinical trial of tasquinimod in myelofibrosis ... The single-arm, multicenter open-label study will evaluate the safety and efficacy of tasquinimod given as mono theraphy to patients with myelofibrosis.