Canakinumab for Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia

Overseen By Guillermo Garcia-Manero

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: IL-1 inhibitors, Steroids

Disqualifiers: Active infection, Pregnancy, 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

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: 2

Duration: Up to 2 years

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of canakinumab, a monoclonal antibody, in treating certain blood disorders such as myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Canakinumab may inhibit the growth and spread of cancer cells. It could benefit individuals with low- to intermediate-risk MDS or those with specific genetic markers related to blood cancers, particularly if they have experienced symptoms like anemia requiring transfusions or have not responded to other treatments. Participants will receive canakinumab injections every 28 days, provided there is no disease progression or serious side effects. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are taking systemic steroids, methotrexate, or other immunosuppressive drugs.

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

Research has shown that canakinumab, a treatment for certain blood disorders like myelodysplastic syndromes and chronic myelomonocytic leukemia, is generally well-tolerated. In studies, patients experienced some side effects, mostly mild to moderate, with serious side effects being rare. For many, the treatment did not cause severe problems. These findings suggest that canakinumab is fairly safe for use in humans, particularly for those with lower-risk conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Canakinumab is unique because it targets inflammation in a new way by blocking a specific protein called interleukin-1 beta (IL-1β), which plays a key role in the inflammation process associated with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Unlike standard treatments like chemotherapy, which often come with harsh side effects, canakinumab is administered as a subcutaneous injection, potentially offering a more tolerable option. Researchers are excited because this approach could reduce inflammation-related symptoms and improve quality of life for patients with fewer side effects.

What evidence suggests that canakinumab might be an effective treatment for myelodysplastic syndromes and chronic myelomonocytic leukemia?

Studies have shown that canakinumab can help manage certain blood disorders, specifically lower-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia. Canakinumab, a monoclonal antibody, targets a substance in the body known as IL-1β, which can cause inflammation and support cancer cell growth. In previous studies, patients treated with canakinumab showed promising results, with some experiencing fewer disease symptoms. Although more research is needed to confirm these findings, this trial will evaluate canakinumab's effectiveness and safety, offering hope for people with these specific blood cancers. ^{1 2 4 6 7}

Who Is on the Research Team?

Guillermo Garcia-Manero

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with low or intermediate-1 risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), who haven't responded to prior treatments like ESAs or HMAs. They should have an ECOG performance status of 2 or less, adequate liver and kidney function, and not be pregnant or breastfeeding. Patients must agree to use contraception if they can have children.

Inclusion Criteria

I have anemia needing blood transfusions in the last 8 weeks.

My kidneys work well enough (creatinine clearance over 30 mL/min).

My previous treatments for my condition, including ESAs or HMAs, did not work.

Exclusion Criteria

I am not pregnant or breastfeeding.

I have not received any treatment for myelodysplastic syndrome (MDS).

I am not pregnant, as confirmed by a test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive canakinumab subcutaneously on day 1 of each 28-day cycle

Up to 2 years

1 visit per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

30 days and then every 6 months

1 visit at 30 days, then biannual visits

What Are the Treatments Tested in This Trial?

Interventions

• Canakinumab

Trial Overview The trial is testing Canakinumab, a monoclonal antibody targeting IL-1β, to see how well it works in treating MDS/CMML that's at a low-to-intermediate risk level. It aims to understand the drug's effect on cancer cell growth and spread.

How Is the Trial Designed?

Group I: Treatment (canakinumab) Experimental Treatment 1 Intervention

Patients receive canakinumab SC on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

Published Research Related to This Trial

In a study involving 37 low-risk myelodysplastic syndromes (MDS) patients, Remicade was found to be well tolerated and showed a variety of hematologic responses, with 8 out of 28 patients demonstrating significant improvements after 4 cycles of treatment.

The treatment resulted in notable outcomes such as increased neutrophil counts and hemoglobin levels, suggesting that Remicade could be a potential option for combination therapy in managing low-risk MDS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remicade as TNF suppressor in patients with myelodysplastic syndromes. Raza, A., Candoni, A., Khan, U., et al.[2019]

Ruxolitinib, a JAK1/JAK2 inhibitor, was found to be safe and well-tolerated in a phase 1 study involving 19 patients with lower-risk myelodysplastic syndrome (MDS), with no dose-limiting toxicities observed at a maximum tolerated dose of 20 mg twice daily.

The treatment resulted in a 22% overall response rate among MDS patients, with some patients showing hematological improvements and a potential correlation between reduced NF-kB activity (measured by pp65 levels) and longer response duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of ruxolitinib in previously treated patients with low or intermediate-1 risk myelodysplastic syndrome with evidence of NF-kB activation. Abaza, Y., Hidalgo-Lopez, JE., Verstovsek, S., et al.[2021]

Therapeutic monoclonal antibodies (mAbs) are showing great promise in treating acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), particularly by targeting resistant leukemic stem cells (LSCs) that contribute to high relapse rates and mortality.

Combining standard chemotherapy with mAbs that specifically target malignant cells or enhance the immune response could significantly improve patient outcomes, as highlighted by ongoing clinical trials and preclinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Antibodies for Myeloid Neoplasms-Current Developments and Future Directions. Schürch, CM.[2023]

Recent advancements in understanding the immune mechanisms behind myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) have led to the identification of new therapeutic targets, improving treatment options for these diseases.

Emerging immune therapies, including monoclonal antibodies and cellular therapeutics, show promise in treating higher-risk MDS and AML, although the best candidates for immune suppressive therapy are still being determined.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Therapies for Myelodysplastic Syndromes and Acute Myeloid Leukemia. Kapoor, S., Champion, G., Basu, A., et al.[2023]

Magrolimab, an antibody that targets CD47, shows clinical activity in treating acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) by promoting macrophage phagocytosis of cancer cells.

Sabatolimab, which inhibits the TIM3 protein, enhances T-cell function and induces tumor cell death, demonstrating promising results in AML/MDS treatment, highlighting the potential of immunotherapy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes. Gallazzi, M., Ucciero, MAM., Faraci, DG., et al.[2022]

Citations

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A Phase 2 Study of Canakinumab in Patients with Lower-Risk ... Here, we report final results of a phase 2 study evaluating the safety and efficacy of canakinumab, an IL-1β inhibitor, in patients with lower- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04239157

Study Details | NCT04239157 | A Phase II, Open-Label, ... This phase II trial studies how well canakinumab works for the treatment of low- or intermediate-risk myelodysplastic syndrome or chronic myelomonocytic ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123084690

A Phase 2 Study of Canakinumab in Patients with Lower- ... We report final results of a phase 2 study evaluating the safety and efficacy of canakinumab, an IL-1β inhibitor, in patients with lower-risk MDS or chronic ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39537648/

The IL-1β inhibitor canakinumab in previously treated lower ... The IL-1β inhibitor canakinumab in previously treated lower-risk myelodysplastic syndromes: a phase 2 clinical trial. Nat Commun. 2024 Nov 13 ...

5. researchgate.net researchgate.net/publication/376154249_A_Phase_2_Study_of_Canakinumab_in_Patients_with_Lower-Risk_Myelodysplastic_Syndromes_or_Chronic_Myelomonocytic_Leukemia

A Phase 2 Study of Canakinumab in Patients with Lower- ... Here, we report final results of a phase 2 study evaluating the safety and efficacy of canakinumab, an IL-1β inhibitor, in patients with lower-risk MDS or ...

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

The IL-1β inhibitor canakinumab in previously treated ... Here the authors report the results of a phase 2 clinical trial of the IL-1β inhibitor canakinumab in previously treated lower-risk MDS.

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04239157/

Clinical Trial: NCT04239157 This phase II trial studies how well canakinumab works for the treatment of low- or intermediate-risk myelodysplastic syndrome or chronic ...