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.
Title
- Brief Title: Canakinumab and Anacitidine for the Treatment of Low or Intermediate Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia
- Official Title: Phase 2, Open-Label, Study of Subcutaneous Canakinumab, an Anti-IL-1B Human Monoclonal Antibody, for Patients With Low or Int-1 Risk IPSS/IPSS-R Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia
Clinical Trial IDs
- ORG STUDY ID:
2019-0339
- SECONDARY ID:
NCI-2019-08494
- SECONDARY ID:
2019-0339
- NCT ID:
NCT04239157
Conditions
- Chronic Myelomonocytic Leukemia
- Myelodysplastic Syndrome
- Recurrent Chronic Myelomonocytic Leukemia
- Recurrent Myelodysplastic Syndrome
- Refractory Chronic Myelomonocytic Leukemia
- Refractory Myelodysplastic Syndrome
Interventions
Drug | Synonyms | Arms |
---|
Canakinumab | ACZ885, Ilaris | Treatment (canakinumab) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (canakinumab) | Experimental | Patients receive canakinumab SC on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | |
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)
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Hematological improvement (HI) |
Time Frame: | After 2 cycles (each cycle is 28 days) |
Safety Issue: | |
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. |
Secondary Outcome Measures
Measure: | Transfusion independence |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | |
Measure: | Duration of response |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Will be summarized using descriptive statistics such as mean, standard deviation, median and range. |
Measure: | Progression-free survival (PFS) |
Time Frame: | Up to 2 years |
Safety Issue: | |
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. |
Measure: | Leukemia-free survival (LFS) |
Time Frame: | Up to 2 years |
Safety Issue: | |
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. |
Measure: | Overall survival (OS) |
Time Frame: | Up to 2 years |
Safety Issue: | |
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. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | M.D. Anderson Cancer Center |
Last Updated
October 23, 2020