RECRUITING

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

Conditions

Chronic Myelomonocytic Leukemia Myelodysplastic Syndrome Recurrent Chronic Myelomonocytic Leukemia Recurrent Myelodysplastic Syndrome Refractory Chronic Myelomonocytic Leukemia Refractory Myelodysplastic Syndrome

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2020-08-25

Study Completion:2026-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04239157

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age ≥ 18 years as MDS and CCUS are very rare conditions in the pediatric setting. * Cohorts 1-3: Diagnosis of MDS according to 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 (Weeks et al, NEJM Evidence in press): ANC \<1.8 or hgb \<12 in females and \<13 in males or a platelet count of \<150. * Cohort 1: Participants need to have not responded to prior therapy with 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. Participants with relapse or progression after any number of cycles of HMA by IWG 2006 criteria will also be candidates. Participants 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 (1) at least 2 units of PRBC for a hemoglobin level less than 8g/dl or symptomatic anemia (hemoglobin \<10g/dL), or (2) any platelet transfusion. * Participants (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 ULN, AST or ALT \</= 3xULN. * Serum creatinine clearance \>30mL/min and no end/stage renal disease (using Cockcroft-Gault). * ECOG performance status \</=2.	* Active infection not adequately responding to appropriate antibiotics. * Prior treatment with IL-1/IL-1r inhibitors * Absolute neutrophil count (ANC) \<0.5x109 k/ul; colony-stimulating factors can be administered prior to study drug initiation. * Female participants who are pregnant or lactating. * Participants 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 participants 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: a. Adequately treated in situ carcinoma of the cervix uteri b. 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. * Participants 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.

Inclusion Criteria

Exclusion Criteria

* Age ≥ 18 years as MDS and CCUS are very rare conditions in the pediatric setting.
* Cohorts 1-3: Diagnosis of MDS according to 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 (Weeks et al, NEJM Evidence in press): ANC \<1.8 or hgb \<12 in females and \<13 in males or a platelet count of \<150.
* Cohort 1: Participants need to have not responded to prior therapy with 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. Participants with relapse or progression after any number of cycles of HMA by IWG 2006 criteria will also be candidates. Participants 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 (1) at least 2 units of PRBC for a hemoglobin level less than 8g/dl or symptomatic anemia (hemoglobin \<10g/dL), or (2) any platelet transfusion.
* Participants (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 ULN, AST or ALT \</= 3xULN.
* Serum creatinine clearance \>30mL/min and no end/stage renal disease (using Cockcroft-Gault).
* ECOG performance status \</=2.

* Active infection not adequately responding to appropriate antibiotics.
* Prior treatment with IL-1/IL-1r inhibitors
* Absolute neutrophil count (ANC) \<0.5x109 k/ul; colony-stimulating factors can be administered prior to study drug initiation.
* Female participants who are pregnant or lactating.
* Participants 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 participants 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: a. Adequately treated in situ carcinoma of the cervix uteri b. 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.
* Participants 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.

Contacts and Locations

Study Contact

Guillermo Garcia-Manero

CONTACT

713-794-3604

ggarciam@mdanderson.org

Principal Investigator

Guillermo Garcia-Manero

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

M D Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: M.D. Anderson Cancer Center

Guillermo Garcia-Manero, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-08-25

Study Completion Date2026-12-31

Study Record Updates

Study Start Date2020-08-25

Study Completion Date2026-12-31

Terms related to this study

Additional Relevant MeSH Terms

Chronic Myelomonocytic Leukemia
Myelodysplastic Syndrome
Recurrent Chronic Myelomonocytic Leukemia
Recurrent Myelodysplastic Syndrome
Refractory Chronic Myelomonocytic Leukemia
Refractory Myelodysplastic Syndrome