Canakinumab for the Prevention of Progression to Cancer in Patients With Clonal Cytopenias of Unknown Significance, IMPACT Study
A Randomized Double-Blind Placebo-Controlled Phase II Multi-Center Study of Inflammation Modification of Canakinumab to Prevent Leukemic Progression of Clonal Cytopenias of Unknown Significance (CCUS): IMPACT Study
2 other identifiers
interventional
110
1 country
6
Brief Summary
This phase II trial tests how well canakinumab works to prevent progression to cancer in patients with clonal cytopenias of unknown significance (CCUS). CCUS is a blood condition defined by a decrease in blood cells. Blood cells are composed of either red blood cells, white blood cells, or platelets. In patients with CCUS, blood counts have been low for a long period of time. Patients with CCUS also have a mutation in one of the genes that are responsible for helping blood cells develop. The combination of genetic mutations and low blood cell counts puts patients with CCUS at a higher risk to develop blood cancers in the future. This transformation from low blood cell counts to cancer may be caused by inflammation in the body. Canakinumab is a monoclonal antibody that may block inflammation in the body by targeting a specific antibody called the anti-human interleukin-1beta (IL-1beta).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Feb 2023
Longer than P75 for phase_2
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 29, 2022
CompletedFirst Posted
Study publicly available on registry
December 8, 2022
CompletedStudy Start
First participant enrolled
February 6, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
January 2, 2026
December 1, 2025
5.9 years
November 29, 2022
December 31, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Time to overt myeloid malignancy
Will be estimated with the non-parametric Kaplan-Meier method to compute the median time as well as the percentage of study participants with a diagnosed hematologic malignancy of myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), chronic myelomonocytic leukemia (CMML)/ acute myeloid leukemia (AML) at landmark time points (e.g., 1-year, 2-years) with corresponding 95% confidence intervals. Since this method will censor patients who die without having developed MDS/MPN/CMML/AML, we will also compute the cumulative incidence of overt myeloid malignancy that accounts for the competing risk of death in the absence of a hematologic malignancy. All randomized patients will be included in the primary endpoint analysis in the arm to which they were randomized (ie, intent-to-treat population).
From the date of randomization until the first date of overt myeloid malignancy diagnosis, assessed up to 6 years
Secondary Outcomes (9)
Hematological overall response rate
6 month assessment
Complete hematological response rate
6 month assessment
Duration of hematological response
From the date of first documented hematological response until the date of documented diagnosis of MDS, MPN, CMML, or AML, assessed up to 6 years
Overall survival
From the date of registration until the date of death from any cause, assessed up to 6 years
Changes in variant allele frequencies (VAFs) of somatic mutations
Up to 6 years
- +4 more secondary outcomes
Study Arms (2)
ARM I (canakinumab)
EXPERIMENTALPatients receive canakinumab SC on study. All patients also undergo ECHO and chest x-ray during screening, collection of blood samples during screening and follow up, and bone marrow biopsy and aspiration throughout the trial.
ARM II (placebo)
PLACEBO COMPARATORPatients receive placebo SC on study. All patients also undergo ECHO and chest x-ray during screening, collection of blood samples during screening and follow up, and bone marrow biopsy and aspiration throughout the trial.
Interventions
Undergo peripheral blood collection
Undergo bone marrow biopsy and aspiration
Undergo chest x-ray
Ancillary studies
Eligibility Criteria
You may qualify if:
- Patients with age \>= 18 with high-risk CCUS
- Must meet ALL the following criteria:
- Unexplained, clinically meaningful cytopenias (greater than 4 months) in one or more of the following lineages: erythroid cells, neutrophils, platelets. Clinically meaningful cytopenia is institution specific and threshold may vary on age, sex, and race. Decision-making should depend upon lab values specific to the institution and supersede public works. Based upon published work, significant cytopenias are defined as the following (must meet criteria in at least one lineage):
- Erythroid Cells:
- Hemoglobin \< 11 g/dL
- White Blood Cells:
- Absolute Neutrophil Count \< 1800/microL and \> 500/microL
- Platelets:
- Platelet Count \< 150,000/microL and \> 50,000/microL
- MDS criteria not fulfilled
- No other evidence of hematological malignancy
- No or only mild (\< 10%) bone marrow dysplasia
- Blast cells \< 5% detected via morphologic examination of blood and/or bone marrow smears which can also be supported by flow cytometry and/or immunohistochemical studies
- Any of the following:
- Isolated somatic spliceosome mutation at any VAF (SRSF2, SF3B1, U2AF1, or ZRSR2)
- +11 more criteria
You may not qualify if:
- Concurrent malignancy requiring active systemic therapy
- Diagnosis of MDS or any other myeloid malignancy in the patient's lifetime
- History of Hypersensitivity to canakinumab or drug of a similar class
- Active infection requiring prompt evaluation and treatment or history of recurrent infections
- Known active or recurrent hepatic disorder including cirrhosis, hepatitis B and C (via positive or indeterminate central laboratory \[lab\] results)
- Subjects with active tuberculosis. In subjects with a history of tuberculosis but without active tuberculosis, if the results of the evaluation require treatment per local guidelines, then the treatment should be initiated before randomization (unless otherwise required by Health Authorities or Institutional Review Board (IRB) in which case curative treatment must be completed prior to screening)
- Subjects with suspected or proven immunocompromised state or infections. If the results of this screening per local treatment guidelines or clinical practice require treatment for said infection then the patient is not eligible. Suspected or proven immunocompromised states or infections include:
- Those with any other medical condition such as active infection, treated or untreated, which in the opinion of the investigator places the subject at an unacceptable risk for participation in immunomodulatory therapy. If in the opinion of the investigator, the patient's immunocompromised state does not pose an unacceptable risk for participation, in the absence of uncontrolled infection, and the patient does not have a history of serious infections (such as tuberculosis); then the patient may participate in this study.
- Known history of testing positive for human immunodeficiency virus (HIV) infections. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test.
- Allogeneic bone marrow or solid organ transplant (history of any or within a certain period of time?)
- Those requiring systemic or local treatment in doses with systemic effects e.g.:
- Prednisone \> 20 mg (or equivalent) oral or intravenous daily for \> 14 days
- Prednisone \> 5 mg and =\< 20 mg (or equivalent) daily for \> 30 days
- Equivalent dose of methotrexate \> 15 mg weekly
- Note: Azathioprine is allowed. Daily glucocorticoid-replacement for conditions such as adrenal or pituitary insufficiency is allowed. Topical, inhaled or local steroid use in doses that are not considered to cause systemic effects are permitted. Steroids for pre-medication related to chemotherapy as per local standard of care are permitted.
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Uma Boratelead
Study Sites (6)
University of Miami
Miami, Florida, 33136, United States
Weill Cornell Medical College
New York, New York, 10021, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
UT Southwestern Medical Center at Dallas
Dallas, Texas, 75235, United States
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Uma M Borate, MD, MS
Ohio State University Comprehensive Cancer Center
Central Study Contacts
The Ohio State University Comprehensive Cancer Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
November 29, 2022
First Posted
December 8, 2022
Study Start
February 6, 2023
Primary Completion (Estimated)
December 31, 2028
Study Completion (Estimated)
December 31, 2028
Last Updated
January 2, 2026
Record last verified: 2025-12
Data Sharing
- IPD Sharing
- Will not share