A Phase II, Open-Label, Study of Subcutaneous Canakinumab, an Anti-IL-1β Human Monoclonal Antibody, for Patients With Low or Int-1 Risk IPSS/IPSS-R Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia
Summary
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.
Detailed description
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.
Arms & interventions
- BiologicalCanakinumab
Given SC
Outcome measures
Primary
Hematological improvement (HI)
Will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey. Will estimate the HI rate for canakinumab, along with the 95% credible intervals. The association between HI rate and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test.
Time frame: After 2 cycles (each cycle is 28 days)
Incidence of adverse events
Will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey. Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median and range. Toxicity type, severity and attribution will be summarized for each patient using frequency tables.
Time frame: Up to 4 weeks
Secondary
Transfusion independence
Time frame: Up to 2 years
Duration of response
Time frame: Up to 2 years
Progression-free survival (PFS)
Time frame: Up to 2 years
Leukemia-free survival (LFS)
Time frame: Up to 2 years
Overall survival (OS)
Time frame: Up to 2 years
Eligibility criteria
Study locations (1)
M D Anderson Cancer Center
Houston, Texas, 77030
References
- Rodriguez-Sevilla JJ, Adema V, Chien KS, Loghavi S, Ma F, Yang H, Montalban-Bravo G, Huang X, Calvo X, Joseph J, Bodden K, Garcia-Manero G, Colla S. The IL-1beta inhibitor canakinumab in previously treated lower-risk myelodysplastic syndromes: a phase 2 clinical trial. Nat Commun. 2024 Nov 13;15(1):9840. doi: 10.1038/s41467-024-54290-2.(PubMed)