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.

PRIMARY OBJECTIVE:

- To assess the clinical activity of canakinumab in patients with low or intermediate-1 myelodysplastic syndrome (MDS) or CCUS.

SECONDARY OBJECTIVES:

• To assess the safety profile of canakinumab in patients with low or intermediate-1 risk by - IPSS or IPSS-R score ≤3.5 MDS, CCUS
• To assess the rate of transfusion independence (TI)
• To assess duration of response

EXPLORATORY OBJECTIVE:

- To assess pharmacodynamic (PD) parameters of canakinumab

OUTLINE:

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

After completion of study treatment, patients are followed up at 30 days and then every 6 months thereafter.

Inclusion Criteria:

• Age ≥ 18 years as MDS and CCUS are very rare conditions in the pediatric setting.

• Cohorts 1-3: Diagnosis of MDS according to WHO 2016 classification and low or intermediate-1 risk by IPSS or IPSS-R with a score of ≤ 3.5.

• Cohort 4: Diagnosis of CCUS defined as:

• Presence of a somatic pathogenic variant associated with hematological malignancy without morphological evidence of myelodysplasia

• Variant allele fraction of greater than or equal to 2% in at least one identified somatic pathogenic variant

• Bone marrow aspirate excluding hematological malignancy and MDS

  • Presence of a cytopenia for >30 days. Cytopenia will be defined using accepted CHRS (Clonal Hematopoiesis Risk Score) criteria (Weeks et al, NEJM Evidence in press): ANC <1.8 or hgb <12 in females and <13 in males or a platelet count of <150.

• Cohort 1: Participants need to have not responded to prior therapy with ESAs or hypomethylating agents (HMAs). These could include azacitidine, decitabine, SGI-110, ASTX727, or CC-486. Patients will need to have received at least 4 cycles of HMA. Participants with relapse or progression after any number of cycles of HMA by IWG 2006 criteria will also be candidates. Participants with evidence of del 5q alteration also are required to have been treated with Lenalidomide.

• Cohort 1: Hemoglobin <10g/dL with symptomatic anemia or transfusion dependency defined as the need for prior transfusion in the past 8 weeks for a hemoglobin level less than 8g/dl.

• Cohort 2: Transfusion dependency defined as the need for prior transfusion in the past 8 weeks of (1) at least 2 units of PRBC for a hemoglobin level less than 8g/dl or symptomatic anemia (hemoglobin <10g/dL), or (2) any platelet transfusion.

• Participants (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.

• Adequate hepatic function with total bilirubin </=3 x ULN, AST or ALT </= 3xULN.

• Serum creatinine clearance >30mL/min and no end/stage renal disease (using Cockcroft-Gault).

• ECOG performance status \