Treatment of low or intermediate-risk myelodysplastic syndromes and chronic myelomonocytic leukemia with canakinumab

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

This study is testing if a new medication called canakinumab can help people with low or intermediate-risk myelodysplastic syndromes and chronic myelomonocytic leukemia feel better and reduce their need for blood transfusions.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 76 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, methotrexate, canakinumab
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT04239157 on ClinicalTrials.gov

What this trial studies

This phase II trial evaluates the effectiveness of canakinumab, a monoclonal antibody, in treating patients with low or intermediate-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Participants will receive subcutaneous injections of canakinumab every 28 days, and the study will assess both the clinical activity and safety profile of the treatment. Additionally, the trial aims to measure the rate of transfusion independence and the duration of response to the therapy. Patients will be monitored for 30 days after treatment and then every six months for follow-up.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older diagnosed with low or intermediate-1 risk MDS or chronic clonal cytopenia of undetermined significance (CCUS).

Not a fit: Patients with high-risk MDS or those who have not been diagnosed with MDS or CCUS may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with low or intermediate-risk MDS and CMML, potentially improving their quality of life and disease management.

How similar studies have performed: While there have been studies on monoclonal antibodies for hematological malignancies, the specific use of canakinumab for this patient population is novel and has not been extensively tested.

Eligibility criteria

Inclusion 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.

Exclusion Criteria:

* 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.

Participants requiring systemic steroids, methotrexate or other immunosuppressive drugs will not be included in the study.

Where this trial is running

Houston, Texas

• M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Guillermo Garcia-Manero — M.D. Anderson Cancer Center
• Study coordinator: Guillermo Garcia-Manero

Conditions Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Recurrent Chronic Myelomonocytic Leukemia; Recurrent Myelodysplastic Syndrome; Refractory Chronic Myelomonocytic Leukemia; Refractory Myelodysplastic Syndrome