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

Trial Summary

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.

How is the drug Canakinumab different from other treatments for myelodysplastic syndromes and chronic myelomonocytic leukemia?

Canakinumab is unique because it targets the immune system by blocking interleukin-1 beta, a protein involved in inflammation, which is different from other treatments that often focus on directly attacking cancer cells or modifying immune checkpoints. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II trial studies how well canakinumab works for the treatment of low- or intermediate-risk myelodysplastic syndrome or chronic myelomonocytic leukemia. Canakinumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread.

Research Team

Guillermo Garcia-Manero

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Immune Therapies for Myelodysplastic Syndromes and Acute Myeloid Leukemia. [2023]

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

Remicade as TNF suppressor in patients with myelodysplastic syndromes. [2019]

3. England 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. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

New Frontiers in Monoclonal Antibodies for the Targeted Therapy of Acute Myeloid Leukemia and Myelodysplastic Syndromes. [2022]