Canakinumab for Clonal Cytopenia

Recruiting in Palo Alto (17 mi)

+5 other locations

Overseen by Uma Borate, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Uma Borate

Must not be taking: Immune modulators, ESAs

Disqualifiers: Concurrent malignancy, MDS, active infection, others

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well canakinumab works to prevent progression to cancer in patients with clonal cytopenias of unknown significance (CCUS). CCUS is a blood condition defined by a decrease in blood cells. Blood cells are composed of either red blood cells, white blood cells, or platelets. In patients with CCUS, blood counts have been low for a long period of time. Patients with CCUS also have a mutation in one of the genes that are responsible for helping blood cells develop. The combination of genetic mutations and low blood cell counts puts patients with CCUS at a higher risk to develop blood cancers in the future. This transformation from low blood cell counts to cancer may be caused by inflammation in the body. Canakinumab is a monoclonal antibody that may block inflammation in the body by targeting a specific antibody called the anti-human interleukin-1beta (IL-1beta).

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.

How is the drug Canakinumab unique for treating Clonal Cytopenia?

Canakinumab is unique because it targets and blocks a specific protein called interleukin-1 beta (IL-1β), which plays a role in inflammation, unlike other treatments that may not specifically target this pathway. This mechanism of action is different from other treatments for clonal cytopenia, which may not focus on IL-1β inhibition. ^{1 2 3 4 5}

Research Team

Uma Borate, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• Canakinumab (Monoclonal Antibodies)

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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Uma Borate

Lead Sponsor

Trials

7

Recruited

310+

Findings from Research

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]

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]

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]

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]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Improvement of immune thrombocytopenia with imatinib therapy following chronic myeloid leukemia. [2023]

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

Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. [2022]

3. England 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. [2018]

4. Germany pubmed.ncbi.nlm.nih.gov

Biomarker analysis in polycythemia vera under interferon-alpha treatment: clonality, EEC, PRV-1, and JAK2 V617F. [2016]

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

Data-driven analysis of JAK2V617F kinetics during interferon-alpha2 treatment of patients with polycythemia vera and related neoplasms. [2021]