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Canakinumab and Azacitidine for the Treatment of Low or Intermediate Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia

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ClinicalTrials.gov Identifier: NCT04239157
Recruitment Status : Not yet recruiting
First Posted : January 23, 2020
Last Update Posted : January 23, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
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.

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 Drug: Azacitidine Biological: Canakinumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : June 1, 2020
Estimated Primary Completion Date : January 31, 2022
Estimated Study Completion Date : January 31, 2022


Arm Intervention/treatment
Experimental: Treatment (canakinumab, azacitidine)
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.
Drug: Azacitidine
Given SC or IV
Other Names:
  • 5 AZC
  • 5-AC
  • 5-Azacytidine
  • 5-AZC
  • Azacytidine
  • Azacytidine, 5-
  • Ladakamycin
  • Mylosar
  • U-18496
  • Vidaza

Biological: Canakinumab
Given SC
Other Names:
  • ACZ885
  • Ilaris




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. Duration of Response [ Time Frame: up to 2 years ]
    Response date to loss of response or last follow up

  2. Progression-Free Survival [ Time Frame: Up to 3 cycles (each cycles is 28 days) ]
    The time from start of treatment to first documentation of disease progression or death due to any cause, whichever occurred first

  3. Overall Survival [ Time Frame: up to 2 years ]
    Time from date of treatment start until date of death due to any cause or last Follow-up



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 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)

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
Houston, Texas, United States, 77030
Contact: Guillermo Garcia-Manero    713-794-3604      
Principal Investigator: Guillermo Garcia-Manero         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Guillermo Garcia-Manero M.D. Anderson Cancer Center

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 )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: January 23, 2020    Key Record Dates
Last Update Posted: January 23, 2020
Last Verified: January 2020

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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
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Leukemia, Myeloid
Myelodysplastic-Myeloproliferative Diseases
Azacitidine
Antibodies, Monoclonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Physiological Effects of Drugs