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
Primary Purpose
Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome, Recurrent Chronic Myelomonocytic Leukemia
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Canakinumab
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Myelomonocytic Leukemia
Eligibility 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)
Sites / Locations
- M D Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (canakinumab)
Arm Description
Patients receive canakinumab SC on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Hematological improvement (HI)
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
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
Transfusion independence
Duration of response
Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
Progression-free survival (PFS)
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)
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)
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.
Full Information
NCT ID
NCT04239157
First Posted
December 31, 2019
Last Updated
August 29, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI), Novartis
1. Study Identification
Unique Protocol Identification Number
NCT04239157
Brief 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
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 25, 2020 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI), Novartis
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome, Recurrent Chronic Myelomonocytic Leukemia, Recurrent Myelodysplastic Syndrome, Refractory Chronic Myelomonocytic Leukemia, Refractory Myelodysplastic Syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment (canakinumab)
Arm Type
Experimental
Arm Description
Patients receive canakinumab SC on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
Canakinumab
Other Intervention Name(s)
ACZ885, Ilaris
Intervention Description
Given SC
Primary Outcome Measure Information:
Title
Hematological improvement (HI)
Description
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.
Time Frame
After 2 cycles (each cycle is 28 days)
Title
Incidence of adverse events
Description
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.
Time Frame
Up to 4 weeks
Secondary Outcome Measure Information:
Title
Transfusion independence
Time Frame
Up to 2 years
Title
Duration of response
Description
Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
Time Frame
Up to 2 years
Title
Progression-free survival (PFS)
Description
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.
Time Frame
Up to 2 years
Title
Leukemia-free survival (LFS)
Description
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.
Time Frame
Up to 2 years
Title
Overall survival (OS)
Description
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.
Time Frame
Up to 2 years
Other Pre-specified Outcome Measures:
Title
Pharmacodynamic (PD) parameters of canakinumab
Description
Will include Correlative studies.
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Guillermo Garcia-Manero
Phone
713-794-3604
Email
ggarciam@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillermo Garcia-Manero
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guillermo Garcia-Manero, MD
Phone
713-794-3604
Email
ggarciam@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Guillermo Garcia-Manero, MD
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center
Learn more about this trial
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
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