Canakinumab for Myelofibrosis

Recruiting at 6 trial locations

Overseen By Ashley Yu

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: John Mascarenhas

Must not be taking: TNFα inhibitors, IL-1 agents, Corticosteroids

Disqualifiers: Active infection, Uncontrolled cardiac issues, Prior malignancy, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Canakinumab, a new treatment for myelofibrosis, a condition where the bone marrow doesn't produce enough healthy blood cells. The study aims to determine if Canakinumab can improve symptoms and manage the disease. Participants will receive the treatment via injection every three weeks over several months. Those diagnosed with myelofibrosis and experiencing symptoms like low hemoglobin or an enlarged spleen might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to potentially benefit from an innovative therapy.

Will I have to stop taking my current medications?

The trial requires that at least two weeks must have passed since the last dose of any myelofibrosis-directed drug treatments, except for hydroxyurea, before joining. If you're on other medications, the protocol doesn't specify, so it's best to discuss with the trial team.

Is there any evidence suggesting that Canakinumab is likely to be safe for humans?

Research shows that Canakinumab has been safely used to treat other conditions. The FDA has approved it for several diseases, indicating it has passed safety checks for those uses. Studies have found that Canakinumab is generally well-tolerated, with upper respiratory tract infections, like a cold, being the most common side effect. Long-term research also supports its safety in treating rare inflammatory diseases such as CAPS, FMF, TRAPS, and MKD/HIDS. This indicates that Canakinumab has been used in people for extended periods without major issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Canakinumab is unique because it targets interleukin-1β, a different approach from the standard treatments for myelofibrosis, which often focus on JAK inhibitors like ruxolitinib. This targeted mechanism may help reduce inflammation and improve symptoms in a novel way. Additionally, canakinumab is administered via subcutaneous injection, which can be more convenient for patients compared to some other treatments that might require more frequent dosing or intravenous administration. Researchers are excited about its potential to offer a new option for patients who may not respond well to existing therapies.

What evidence suggests that Canakinumab might be an effective treatment for myelofibrosis?

Research has shown that Canakinumab, a drug that reduces inflammation, might help treat myelofibrosis, a rare bone marrow disorder. In other conditions, such as CAPS (a rare inflammatory syndrome), Canakinumab has proven safe and effective over the long term. This drug blocks a protein in the body that causes inflammation, which is believed to play a role in myelofibrosis. Early results in patients with myelofibrosis suggest possible benefits, but further research is needed to confirm its effectiveness for this condition. ^{2 6 7 8 9}

Who Is on the Research Team?

John Mascarenhas, MD

Principal Investigator

MOUNT SINAI HOSPITAL

Are You a Good Fit for This Trial?

Adults diagnosed with primary myelofibrosis or related conditions, who cannot take ruxolitinib/fedratinib due to low platelet counts or lack of response. They must have adequate organ function, not be eligible for certain other treatments, and agree to use contraception. Excluded are those with unstable heart disease, recent live vaccinations, high-dose steroid treatment within 14 days, active infections including HIV and hepatitis B/C, or any serious medical/psychiatric issues.

Inclusion Criteria

I have been diagnosed with primary myelofibrosis or its advanced stages after ET/PV.

I have low hemoglobin, need regular blood transfusions, have an enlarged spleen, or a high MF-SAF score.

I agree to sign the consent form and follow the study's schedule and rules.

Exclusion Criteria

I have had cancer before, but it was either cured locally or has been inactive for over a year.

I have had a bone marrow or organ transplant before.

I have a known heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Canakinumab administered as a subcutaneous injection on day 1 of a 21-day cycle for a core study period of 8 cycles

24 weeks

8 visits (in-person, every 3 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Canakinumab

Trial Overview The trial is testing Canakinumab given as a subcutaneous injection every three weeks over eight cycles in patients with myelofibrosis. The study will assess the drug's effectiveness and safety through an interim analysis after ten patients are enrolled and may stop if there's excessive toxicity or no responses.

How Is the Trial Designed?

Group I: Canakinumab Experimental Treatment 1 Intervention

Canakinumab will be given by subcutaneous injection (SC) injection at a starting dose of 200 mg (one 150 mg/mL syringe and one 50 mg/0.5 mL syringe) every 3 weeks.

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

Approved in European Union as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Approved in United States as Ilaris for:

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Familial Cold Autoinflammatory Syndrome (FCAS)
• Muckle-Wells Syndrome (MWS)
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Systemic Juvenile Idiopathic Arthritis (SJIA)
• Adult-Onset Still's Disease (AOSD)

Who Is Running the Clinical Trial?

John Mascarenhas

Lead Sponsor

Trials

10

Recruited

220+

Published Research Related to This Trial

Ruxolitinib remains the only approved treatment for classic Philadelphia chromosome negative myeloproliferative neoplasms, but new therapies like ropeginterferon alfa-2b have recently been approved for polycythemia vera, indicating progress in treatment options.

Several new JAK inhibitors and other agents are in clinical development for myelofibrosis, focusing not only on symptom relief but also on improving anemia, showcasing a shift in treatment goals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel treatment strategies for myeloproliferative neoplasms. Bose, P., Masarova, L., Verstovsek, S.[2019]

Pacritinib is a potent inhibitor of JAK2 and FLT3 that shows clinical efficacy in treating myelofibrosis without causing myelosuppression, which is a common side effect of other JAK inhibitors.

The drug selectively inhibits JAK2 while sparing JAK1, and it also reduces harmful cytokines, suggesting potential therapeutic benefits in other blood cancers and inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive kinase profile of pacritinib, a nonmyelosuppressive Janus kinase 2 inhibitor. Singer, JW., Al-Fayoumi, S., Ma, H., et al.[2022]

Pacritinib has shown promising efficacy in treating myelofibrosis (MF), with 31% of patients experiencing a significant reduction in spleen volume and 42% showing improvement in spleen size through physical examination after 24 weeks.

The treatment demonstrated a favorable safety profile, particularly for patients with preexisting anemia and thrombocytopenia, although common side effects included diarrhea and nausea, leading to treatment discontinuation in 26% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. Komrokji, RS., Seymour, JF., Roberts, AW., et al.[2022]

Ruxolitinib has been a key treatment for myelofibrosis for over a decade, but the emergence of new JAK inhibitors like fedratinib and pacritinib necessitates a clear understanding of what constitutes 'failure' of ruxolitinib therapy.

A consensus among experts suggests that in cases of ruxolitinib failure, either continuing ruxolitinib with an additional agent or switching to a different JAK inhibitor may be beneficial, highlighting the need for personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moving beyond ruxolitinib failure in myelofibrosis: evolving strategies for second line therapy. Bose, P., Kuykendall, AT., Miller, C., et al.[2023]

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05467800/study-of-canakinumab-in-patients-with-myelofibrosis

Study of Canakinumab in Patients With Myelofibrosis This is an open label, multicenter, phase 2 trial of Canakinumab in patients with primary myelofibrosis (PMF), post essential thrombocythemia/polycythemia vera ...

2. mayo.edu mayo.edu/research/clinical-trials/cls-20565695

Study of Canakinumab in Patients With Myelofibrosis The purpose of this study is to estimate the effectiveness of Canakinumab treatment in patients with primary myelofibrosis (PMF), post PV-MF (Post-Polycythemia ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-06537

Canakinumab for the Treatment of Primary Myelofibrosis ... This phase II trial evaluates the safety and effectiveness of canakinumab for the treatment of patients with primary myelofibrosis, post polycythemia vera ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10875478/

Long-term safety and effectiveness of canakinumab in ... Conclusion. Data from this analysis confirm the long-term safety and effectiveness of canakinumab for the treatment of CAPS, FMF, TRAPS and MKD ...

5. withpower.com withpower.com/trial/phase-2-et-mf-6-2022-9ad11

Canakinumab for Myelofibrosis This is an open label, multicenter, phase 2 trial of Canakinumab in patients with primary myelofibrosis (PMF), post essential thrombocythemia/polycythemia ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/125319s047lbl.pdf

ILARIS (canakinumab) Label - accessdata.fda.gov Overall, the efficacy and safety of ILARIS in pediatric and adult patients were comparable. Infections of the upper respiratory tract were the most ...

7. novartis.com novartis.com/us-en/sites/novartis_us/files/ilaris.pdf

Ilaris The safety of ILARIS compared to placebo in SJIA patients was investigated ... data regarding infant serum levels of canakinumab at birth and the ...

8. medchemexpress.com medchemexpress.com/canakinumab.html?srsltid=AfmBOoqVnHAuOzT3GUM7gizUKYjQ4wCwCdz9Iq-KzE1opSiX7OdaDFuB

Canakinumab (Ilaris) | Anti-IL-1β Monoclonal Antibody Canakinumab (ACZ885) is a recombinant human anti-IL-1β monoclonal antibody. Canakinumab shows IC50 values of 43.6 and 40.8 pM for human and marmoset IL-1β, ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01213641?cond=ilaris&viewType=Table&rank=7

A Registry Study of Ilaris (Canakinumab) Patients The purpose of this observational study is to collect additional information regarding long-term safety and effectiveness of Ilaris in the treatment of CAPS ...