Description:
This phase II trial studies how well canakinumab and azacitidine work for the treatment of
low- or intermediate-risk myelodysplastic syndrome or chronic myelomonocytic leukemia.
Immunotherapy with canakinumab, may induce changes in body's immune system and may interfere
with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as
azacitidine works in different ways to stop the growth of cancer cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. Giving canakinumab
and azacitidine may work better in controlling the disease.
Title
- Brief Title: Canakinumab and Azacitidine 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
- SECONDARY ID:
P30CA016672
- 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 |
|---|
| Azacitidine | 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza | Treatment (canakinumab, azacitidine) |
| Canakinumab | ACZ885, Ilaris | Treatment (canakinumab, azacitidine) |
Purpose
This phase II trial studies how well canakinumab and azacitidine work for the treatment of
low- or intermediate-risk myelodysplastic syndrome or chronic myelomonocytic leukemia.
Immunotherapy with canakinumab, may induce changes in body's immune system and may interfere
with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as
azacitidine works in different ways to stop the growth of cancer cells, either by killing the
cells, by stopping them from dividing, or by stopping them from spreading. Giving canakinumab
and azacitidine may work better in controlling the disease.
Detailed Description
PRIMARY OBJECTIVE:
I. To assess the clinical activity, hematological improvement (HI) 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. To assess the safety and tolerability of canakinumab including:
IIa. Adverse events with particular emphasis on occurrence and type of infections.
IIb. Hospitalizations. IIc. Therapy discontinuation. III. Transfusion independence. IV.
Duration of response. V. Progression-free survival (PFS), leukemia-free survival (LFS) and
overall survival (OS).
EXPLORATORY OBJECTIVES:
I. Correlative studies (pharmacodynamic [PD] parameters of canakinumab).
OUTLINE:
Patients receive canakinumab subcutaneously (SC) on day 1. Patients not responding to
canakinumab after 4 cycles, may receive azacitidine SC or intravenously (IV) on days 1-3. If
azacitidine is added after cycle 4, patients receive canakinumab SC on day 4. 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, azacitidine) | Experimental | Patients receive canakinumab SC on day 1. Patients not responding to canakinumab after 4 cycles, may receive azacitidine SC or IV on days 1-3. If azacitidine is added after cycle 4, patients receive canakinumab SC on day 4. 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 and:
- Previously untreated and with white blood cells (WBC) < 12 X 10 k/ul for patients with
CMML (dysplastic CMML)
- Previously treated. Patients need to have relapsed or progressed after prior therapy
with erythropoietin stimulating agents (ESAs), lenalidomide if del(5q) MDS or no
response after at least 4 cycles of decitabine or 6 cycles of hypomethylating
agent-based therapy, or relapse or progression after any number of cycles
- Hemoglobin < 10 g/dL or transfusion dependency defined as the need for prior
transfusion in the past 8 weeks
- 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:
- 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: | Duration of Response |
| Time Frame: | up to 2 years |
| Safety Issue: | |
| Description: | Response date to loss of response or last follow up |
| Measure: | Progression-Free Survival |
| Time Frame: | Up to 3 cycles (each cycles is 28 days) |
| Safety Issue: | |
| Description: | The time from start of treatment to first documentation of disease progression or death due to any cause, whichever occurred first |
| Measure: | Overall Survival |
| Time Frame: | up to 2 years |
| Safety Issue: | |
| Description: | Time from date of treatment start until date of death due to any cause or last Follow-up |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | M.D. Anderson Cancer Center |
Last Updated
January 21, 2020
