Canakinumab for the Treatment of Low or Intermediate Risk Myelodysplastic Syndrome

Inclusion Criteria

• Age ≥ 18 years as MDS and CCUS are very rare conditions in the pediatric setting
• COHORT 1-3: Diagnosis of MDS according to World Health Organization (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: absolute neutrophil count (ANC) <1.8 or hemoglobin (hgb) <12 in females and <13 in males or a platelet count of <150
• COHORT 1: Patients need to have not responded to prior therapy with erythropoiesis-stimulating agent (ESAs) or hypomethylating agents (HMAs). These could include azacitidine, decitabine, SGI110, ASTX727, or CC-486. Patients will need to have received at least 4 cycles of HMA. Patients with relapse or progression after any number of cycles of HMA by IWG 2006 criteria will also be candidates. Patients 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 at least 2 units of PRBC for a hemoglobin level less than 8g/dl or symptomatic anemia (hemoglobin <10g/dL)
• Patient (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 upper limit of normal (ULN), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) </= 3 x ULN
• Serum creatinine clearance >30mL/min and no end/stage renal disease (using Cockcroft-Gault)
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Exclusion Criteria

• Active infection not adequately responding to appropriate antibiotics
• Prior treatment with IL-1/IL-1r inhibitors
• Absolute neutrophil count (ANC) < 0.5 X 10^9 k/ul; colony-stimulating factors can be administered prior to study drug initiation
• Female patients who are pregnant or lactating
• Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study. Reproductive potential is defined as no previous surgical sterilization or females that are not post-menopausal for 12 months
• Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
• History of an active malignancy within the past 2 years prior to study entry, with the exception of: * Adequately treated in situ carcinoma of the cervix uteri * Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin or any other malignancy with a life expectancy of more than 2 years
• Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy (within 14 days of initiating study treatment)
• Known history of testing positive for Human Immunodeficiency Virus (HIV) infections
• Patients requiring systemic steroids, methotrexate or other immunosuppressive drugs will not be included in the study