Canakinumab for Clonal Cytopenia

Recruiting at 5 trial locations

Overseen By The Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Uma Borate

Must not be taking: Immune modulators, ESAs

Disqualifiers: Concurrent malignancy, MDS, active infection, others

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: 1

Duration: 6 months

110 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether canakinumab, a medication that may reduce inflammation, can help prevent blood cancer in individuals with clonal cytopenias of unknown significance (CCUS). CCUS is a condition characterized by low blood cell counts and genetic changes that increase cancer risk. Participants will receive either canakinumab or a placebo to determine if the medication can halt progression to cancer. Ideal candidates have long-standing low blood cell counts and specific genetic mutations but no current blood cancer. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain immune-modulating agents and erythropoietin stimulating agents (ESA) are not allowed, so you may need to discuss your specific medications with the trial team.

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

Research has shown that canakinumab is generally safe. In one study with 25 patients, the treatment was well-tolerated, with no participants needing to stop, although some experienced minor side effects. Canakinumab's approval for other conditions further suggests its safety. Clinical trials have demonstrated that taking canakinumab every two weeks is both safe and effective. Overall, these findings support its safety for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for CCUS?

Unlike the standard treatments for clonal cytopenia, which often focus on managing symptoms or using broad immunosuppressive therapies, canakinumab targets a specific pathway in the immune system. Canakinumab is a monoclonal antibody that blocks interleukin-1 beta, a protein involved in inflammation and immune responses. This targeted approach could potentially offer more precise control over the condition with fewer side effects. Researchers are excited about canakinumab because it represents a shift towards more personalized medicine, aiming to address the underlying cause of clonal cytopenia rather than just alleviating symptoms.

What evidence suggests that canakinumab might be an effective treatment for clonal cytopenia?

Research has shown that canakinumab, which participants in this trial may receive, might help people with clonal cytopenias of unknown significance (CCUS) by reducing inflammation, a factor that can sometimes lead to cancer. In earlier studies, canakinumab improved hemoglobin levels in patients with anemia, a common issue in CCUS. The drug was generally well-tolerated, causing few side effects. Although only a small number of patients experienced a full response, these improvements suggest that canakinumab could be helpful in managing the condition. ^{1 3 6 7 8}

Who Is on the Research Team?

Uma Borate, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults (18+) with clonal cytopenias of unknown significance (CCUS), a condition where blood cell counts are low due to genetic mutations, increasing the risk of developing blood cancers. Participants must have specific gene mutations, adequate organ function, and controlled blood pressure. They cannot be HIV positive or on certain medications like high-dose steroids or methotrexate, nor can they have active infections or other malignancies.

Inclusion Criteria

I have had low blood counts for more than 4 months without a known reason.

No or only mild (< 10%) bone marrow dysplasia

My tests show mutations in TET2, DMNT3A, or ASXL1 and another known mutation.

Exclusion Criteria

I am currently receiving treatment for another cancer.

I have active tuberculosis.

I have been diagnosed with MDS or another myeloid cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive canakinumab or placebo subcutaneously, with regular blood sample collection and bone marrow biopsy throughout the trial

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including echocardiogram and chest x-ray

Up to 6 years

Annual visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Canakinumab

Trial Overview The trial is testing Canakinumab's effectiveness in preventing CCUS from progressing to cancer by targeting inflammation caused by an antibody called IL-1beta. It involves collecting biospecimens, bone marrow procedures, imaging tests like chest X-rays and echocardiography, comparing Canakinumab against a placebo while assessing quality of life.

How Is the Trial Designed?

Group I: ARM I (canakinumab) Experimental Treatment 6 Interventions

Patients receive canakinumab SC on study. All patients also undergo ECHO and chest x-ray during screening, collection of blood samples during screening and follow up, and bone marrow biopsy and aspiration throughout the trial.

Group II: ARM II (placebo) Placebo Group 6 Interventions

Patients receive placebo SC on study. All patients also undergo ECHO and chest x-ray during screening, collection of blood samples during screening and follow up, and bone marrow biopsy and aspiration throughout the trial.

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?

Uma Borate

Lead Sponsor

Trials

7

Recruited

310+

Published Research Related to This Trial

In a follow-up study of 83 patients (43 with polycythemia vera and 40 with essential thrombocythemia) treated with pegylated interferon α-2a for a median of 42 months, 76% of PV patients and 77% of ET patients achieved a complete hematologic response.

The study found that 18% of PV patients and 17% of ET patients achieved a complete molecular response, indicating that the treatment can lead to significant long-term benefits, although the presence of certain mutations may affect the treatment's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. Quintás-Cardama, A., Abdel-Wahab, O., Manshouri, T., et al.[2022]

Treatment with PEGylated interferon-alpha2 (IFN) can lead to significant reductions in the JAK2V617F allele burden in patients with essential thrombocythemia and polycythemia vera, with some achieving undetectable levels of the mutation.

The study analyzed 66 patients and found that early intervention with IFN is crucial, as untreated patients showed an exponential increase in the JAK2V617F allele burden, while those treated with IFN experienced a decrease, suggesting that starting treatment sooner may improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Data-driven analysis of JAK2V617F kinetics during interferon-alpha2 treatment of patients with polycythemia vera and related neoplasms. Pedersen, RK., Andersen, M., Knudsen, TA., et al.[2021]

The combination of pegylated interferon-α 2a with Imatinib mesylate was well tolerated in a phase I/II study involving 15 patients with chronic phase CML who were resistant to Imatinib, indicating a promising safety profile.

This treatment led to a significant reduction in Ph1(+) bone marrow metaphases and resulted in long-term complete cytogenetic response (CCyR) in 2 patients, with a median follow-up of 43 months showing a 93% survival rate, suggesting its efficacy in overcoming resistance to Imatinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated IFN-α2a combined to imatinib mesylate 600mg daily can induce complete cytogenetic and molecular responses in a subset of chronic phase CML patients refractory to IFN alone or to imatinib 600mg daily alone. Nicolini, FE., Hayette, S., Legros, L., et al.[2018]

In a study of three polycythemia vera patients undergoing pegylated-interferon (rIFNalpha) treatment, all patients transitioned from clonal to polyclonal hematopoiesis, indicating a positive response to the therapy.

Despite the shift to polyclonal hematopoiesis, markers of the disease such as Jak2V617F expression and Epo-independent colony growth remained detectable, suggesting that while rIFNalpha treatment is beneficial, it does not completely eliminate the underlying disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker analysis in polycythemia vera under interferon-alpha treatment: clonality, EEC, PRV-1, and JAK2 V617F. Steimle, C., Lehmann, U., Temerinac, S., et al.[2016]

A 55-year-old man with immune thrombocytopenia (ITP) developed chronic myeloid leukemia (CML) four years after his initial diagnosis, and his CML was effectively managed with a daily dose of 400 mg of the tyrosine kinase inhibitor (TKI) imatinib mesylate, leading to a major molecular response.

The TKI therapy not only controlled the CML but also improved the patient's ITP, suggesting that the treatment may have had beneficial off-target effects on the autoimmune response associated with ITP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of immune thrombocytopenia with imatinib therapy following chronic myeloid leukemia. Nakamura, Y., Itoh, Y., Wakimoto, N.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05641831

Study Details | NCT05641831 | Canakinumab for the ... This phase II trial tests how well canakinumab works to prevent progression to cancer in patients with clonal cytopenias of unknown significance (CCUS).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11561093/

The IL-1β inhibitor canakinumab in previously treated ... Canakinumab was safe and well-tolerated, with no dose reductions or treatment discontinuation during the study. Cytopenia (occurring in 64% of ...

3. ashpublications.org ashpublications.org/ashclinicalnews/news/8438/IL-1-Inhibitor-Canakinumab-May-Be-Effective-in

IL-1β Inhibitor Canakinumab May Be Effective in Specific ... The overall response rate was 17.4%; four of 23 evaluable patients responded with all responses including hematologic improvement. Of the four ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10758744/

Effects of IL-1β inhibition on anemia and clonal ... Canakinumab treatment is associated with improved hemoglobin response in patients with concurrent anemia and CH mutations.

5. withpower.com withpower.com/trial/phase-2-leukopenia-2023-abde5

Canakinumab for Clonal Cytopenia The study found that 18% of PV patients and 17% of ET patients achieved a complete molecular response, indicating that the treatment can lead to significant ...

6. novartis.com novartis.com/ca-en/sites/novartis_ca/files/ILARIS_PM_20250619_e.pdf

product monograph including patient medication information safety of canakinumab has been studied in the marmoset. No undesirable effects of canakinumab were seen following twice weekly ...

7. go.drugbank.com go.drugbank.com/drugs/DB06168

Canakinumab: Uses, Interactions, Mechanism of Action Clinical trials have established the administration of canakinumab every 2 weeks to be safe and effective, offering a considerable advantage over the existing ...

8. ilarishcp.com ilarishcp.com/stills-disease

Still's Disease Treatment | ILARIS® (canakinumab) HCP In clinical trials, ILARIS was proven to help manage symptoms in patients with Still's disease · Safety profile of ILARIS in patients aged 2 years and older ...