Recruiting

Phase 2

CanakinumabCanakinumab for the Prevention of Progression to Cancer in Patients With Clonal Cytopenias of Unknown Significance, IMPACT Study

Sponsor:

Uma Borate

Code:

NCT05641831

Conditions

Clonal Cytopenia of Undetermined Significance

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Biospecimen Collection

Bone Marrow Aspiration and Biopsy

Canakinumab

Chest Radiography

Echocardiography

Study Details

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).

Conditions

Clonal Cytopenia of Undetermined Significance

Study ID

NCT05641831

Start date

Feb 6, 2023

Status verified date

Dec, 2025

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Dec 31, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

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)
Isolated TP53 mutation greater than 5% VAF
At least 1 mutation in TET2, DMNT3A, or ASXL1 at any VAF coupled with at least 1 other known myeloid pathogenic somatic mutation or known pathogenic germline mutation that predisposes to myeloid malignancy as determined by next generation sequencing and bone marrow biopsy
A TET2, DMNT3A, or ASXL1 greater than 10% VAF coupled with another TET2, DMNT3A, or ASXL1 greater than 10% VAF
The presence of two or more known myeloid pathogenic somatic or germline mutations (other than TET2, ASXL1, DMNT3A, TP53, or spliceosome mutations) greater than 10% VAF
Ability to understand and willingness to sign the written informed consent document
Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
Patients with a history of hypertension or active hypertension are strongly encouraged to optimize blood pressure control
Creatinine clearance greater than 45 ml/min using Cockcroft-Gault
Total bilirubin =< 1.5 x ULN
Aspartate transaminase (AST) < 3 x ULN
Alanine transaminase (ALT) < 3 x ULN

Exclusion Criteria:

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.
Live or attenuated vaccination within 3 months prior to first dose of study drug (e.g. Measles/Mumps/Rubella \[MMR\], Yellow Fever, Rotavirus, Smallpox, etc.) and after initiation of canakinumab treatment
Use of erythropoietin stimulating agents (ESA) or growth factors within four weeks prior to the start of the study
Pregnant or nursing women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic methods of contraception during dosing of study treatment and for up to 130 days after last dose of study drug. Basic contraception methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least 6 weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject
Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/ vaginal suppository
Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS). In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. Prior to entry into this study, cisplatin-based chemotherapy, which may be toxic to the fetus, may be given. The time between the end of cisplatin-based chemotherapy and the start canakinumab/placebo treatment is variable, resulting in a variable need for continuation of highly effective contraception. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks prior to first dose of study drug. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the Informed Consent Form (ICF).

Study Design

Enrollment

110 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: ARM I (canakinumab)

Patients 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.

placebo comparator: ARM II (placebo)

Patients 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

Biospecimen Collection

Undergo peripheral blood collection

Bone Marrow Aspiration and Biopsy

Undergo bone marrow biopsy and aspiration

Canakinumab

Given SC

Chest Radiography

Undergo chest x-ray

Echocardiography

Undergo ECHO

Placebo Administration

Given SC

Quality-of-Life Assessment

Ancillary studies

Primary outcome measure

Time to overt myeloid malignancy [ Time Frame: From the date of randomization until the first date of overt myeloid malignancy diagnosis, assessed up to 6 years ]

Central Contacts and Locations

Central contacts

The Ohio State University Comprehensive Cancer Center

800-293-5066 OSUCCCClinicaltrials@osumc.edu

Locations

University of Miami

Recruiting

Miami, Florida, United States, 33136

Contacts

Namrata Chandhok, MD

305-243-8238 nxc691@miami.edu

Principal Investigator:

Namrata S Chandhok, MD

Weill Cornell Medical College

Recruiting

New York, New York, United States, 10021

Contacts

Pinkal Desai, M.D.

646-962-2700

Principal Investigator:

Pinkal Desai, M.D.

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Tamanna Haque, MD

646-608-4166 haquet1@mskcc.org

Principal Investigator:

Tamanna Haque, MD

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Uma M. Borate, MD, MS

614-293-3316 borate.2@osu.edu

Principal Investigator:

Uma M. Borate, MD, MS

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Vanderbilt University Medical Center

1-800-811-8480 cip@vumc.org

Principal Investigator:

Ashwin Kishtagari, MD

UT Southwestern Medical Center at Dallas

Recruiting

Dallas, Texas, United States, 75235

Contacts

Donglan Xia, PhD, BSN

214-645-9656 Donglan.Xia@utsouthwestern.edu

Silviya Meletath, MD, MBS

909-560-9597 silviya.meletath@utsouthwestern.edu

Principal Investigator:

Yazan Madanat, MD

More Information

Sponsor

Uma Borate

Last update posted

Jan 2, 2026

Last verified

Dec, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Uma Borate on 2026-01-02.