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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
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Study Description
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Brief Summary:
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.

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

Detailed Description:

PRIMARY OBJECTIVE:

I. To assess the clinical activity of canakinumab in patients with low or intermediate-1 myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML).

SECONDARY OBJECTIVES:

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).

EXPLORATORY OBJECTIVE:

I. Correlative studies (pharmacodynamic [PD] parameters of canakinumab).

OUTLINE:

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

Drug Information available for: Canakinumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Treatment (canakinumab)
Patients receive canakinumab SC on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
 Biological: Canakinumab
Given SC
Other Names:
  • ACZ885
  • Ilaris


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Transfusion independence [ Time Frame: Up to 2 years ]
  2. Duration of response [ Time Frame: Up to 2 years ]
    Will be summarized using descriptive statistics such as mean, standard deviation, median and range.

  3. 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.

  4. 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.

  5. 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.


Other Outcome Measures:
  1. Pharmacodynamic (PD) parameters of canakinumab [ Time Frame: Up to 2 years ]
    Will include Correlative studies.


Eligibility Criteria
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Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Guillermo Garcia-Manero 713-794-3604 ggarciam@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Guillermo Garcia-Manero, MD    713-794-3604    ggarciam@mdanderson.org   
Principal Investigator: Guillermo Garcia-Manero, MD         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Novartis
Investigators
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Principal Investigator: Guillermo Garcia-Manero M.D. Anderson Cancer Center
More Information
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Additional Information:

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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04239157    
Other Study ID Numbers: 2019-0339
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Preleukemia
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Syndrome
Recurrence
Disease
Pathologic Processes
 Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Chronic Disease