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
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04239157|
Recruitment Status : Recruiting
First Posted : January 23, 2020
Last Update Posted : December 9, 2022
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Chronic Myelomonocytic Leukemia Myelodysplastic Syndrome Recurrent Chronic Myelomonocytic Leukemia Recurrent Myelodysplastic Syndrome Refractory Chronic Myelomonocytic Leukemia Refractory Myelodysplastic Syndrome||Biological: Canakinumab||Phase 2|
I. To assess the clinical activity of canakinumab in patients with low or intermediate-1 myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML).
I. To study the safety profile of canakinumab in patients with low or intermediate-1 MDS or CMML.
II. Rate of transfusion independence. III. Duration of response. IV. Progression-free survival (PFS), leukemia-free survival (LFS) and overall survival (OS).
I. Correlative studies (pharmacodynamic [PD] parameters of canakinumab).
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||August 25, 2020|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||December 31, 2023|
Experimental: Treatment (canakinumab)
Patients receive canakinumab SC on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Hematological improvement (HI) [ Time Frame: After 2 cycles (each cycle is 28 days) ]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.
- Incidence of adverse events [ Time Frame: Up to 4 weeks ]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.
- Transfusion independence [ Time Frame: Up to 2 years ]
- Duration of response [ Time Frame: Up to 2 years ]Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
- Progression-free survival (PFS) [ Time Frame: Up to 2 years ]Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-time event endpoints by important subgroups will be made using the log-rank tests.
- Leukemia-free survival (LFS) [ Time Frame: Up to 2 years ]Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-time event endpoints by important subgroups will be made using the log-rank tests.
- Overall survival (OS) [ Time Frame: Up to 2 years ]Will be estimated using the method of Kaplan and Meier. Comparisons of time-to-time event endpoints by important subgroups will be made using the log-rank tests.
- Pharmacodynamic (PD) parameters of canakinumab [ Time Frame: Up to 2 years ]Will include Correlative studies.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Diagnosis of MDS or CMML according to World Health Organization (WHO) and low or intermediate-1 risk by International Prognostic Scoring System (IPSS) or revised International Prognostic Scoring System (IPSS-R) with a score of =< 3.5
- Patients need to have not responded to prior therapy with erythrocyte stimulating agents (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. Patients with relapse or progression after any number of cycles of HMA by International Working Group (IWG) 2006 criteria will also be candidates. Patients with evidence of del 5q alteration also are required to have been treated with lenalidomide
- Hemoglobin < 10 g/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 8 g/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
- Total bilirubin =< 3 X upper limit of normal (ULN)
- Aspartate transaminase (AST) or alanine transferase (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
- Hydroxyurea for control of leukocytosis is allowed at any time prior to or during study if considered to be in the best interest of the patient
- No prior therapy for MDS
- Uncontrolled infection not adequately responding to appropriate antibiotics
- Absolute neutrophil count (ANC) < 0.5 X 10^9 k/ul
- 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
- Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy (within 14 days of initiating study treatment)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04239157
|Contact: Guillermo Garcia-Manerofirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Guillermo Garcia-Manero, MD 713-794-3604 email@example.com|
|Principal Investigator: Guillermo Garcia-Manero, MD|
|Principal Investigator:||Guillermo Garcia-Manero||M.D. Anderson Cancer Center|
|Responsible Party:||M.D. Anderson Cancer Center|
|Other Study ID Numbers:||
NCI-2019-08494 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2019-0339 ( Other Identifier: M D Anderson Cancer Center )
|First Posted:||January 23, 2020 Key Record Dates|
|Last Update Posted:||December 9, 2022|
|Last Verified:||December 2022|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Neoplasms by Histologic Type
Bone Marrow Diseases