Canakinumab for Myelofibrosis

Recruiting at 7 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

Trial Summary

What is the purpose of this trial?

This is an open label, multicenter, phase 2 trial of Canakinumab in patients with primary myelofibrosis (PMF), post essential thrombocythemia/polycythemia vera related MF (Post ET/PV MF). Eligible patients will receive Canakinumab administered as a subcutaneous injection on day 1 of a 21 day cycle for a core study period of 8 cycles. 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. The interim analysis will be performed when the number of enrolled patients reaches 10. If no responses OR 4 or more patients have unacceptable toxicity, the study will not proceed to the second stage. If the total number of patients reaches the maximum sample size of 26, the treatment is deemed acceptable if the number of responses in the efficacy endpoint are greater than 3, and the number of toxicities are less than 7.

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.

How is the drug Canakinumab different from other treatments for myelofibrosis?

Canakinumab is unique because it targets interleukin-1 (a protein involved in inflammation), which is different from most other myelofibrosis treatments that focus on inhibiting Janus kinase (JAK) pathways. This novel approach may offer benefits for patients who do not respond well to existing JAK inhibitors. ^{1 2 3 4 5}

Research Team

John Mascarenhas, MD

Principal Investigator

MOUNT SINAI HOSPITAL

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Comprehensive kinase profile of pacritinib, a nonmyelosuppressive Janus kinase 2 inhibitor. [2022]

2. England pubmed.ncbi.nlm.nih.gov

PTK787/ZK 222584, a small molecule tyrosine kinase receptor inhibitor of vascular endothelial growth factor (VEGF), has modest activity in myelofibrosis with myeloid metaplasia. [2012]

3. Japan pubmed.ncbi.nlm.nih.gov

Novel treatment strategies for myeloproliferative neoplasms. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Results of a phase 2 study of pacritinib (SB1518), a JAK2/JAK2(V617F) inhibitor, in patients with myelofibrosis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Moving beyond ruxolitinib failure in myelofibrosis: evolving strategies for second line therapy. [2023]