- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02783547
Combination Therapy of SyB C-1101 and Azacytidine in Patients With Myelodysplastic Syndrome
A Phase 1, Open Label, Multicentre Clinical Trial of SyB C-1101 in Combination With Azacytidine in Patients With Myelodysplastic Syndrome
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Phase
- Phase 1
Contacts and Locations
Study Locations
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Aichi
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Nagoya, Aichi, Japan
- Research Site
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Gifu
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Kakamigahara, Gifu, Japan
- Research Site
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Miyagi
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Sendai, Miyagi, Japan
- Research Site
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Tokyo
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Shinagawa, Tokyo, Japan
- Research Site
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria
Patients satisfying all the following criteria will be included:
- Histologically or cytologically diagnosed with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) according to World Health Organization (WHO) Classification or French-American-British (FAB) Classification. As for patients with refractory anemia with excess of blasts in transformation (RAEB-t), however, the peripheral blood white blood cell count is ≤ 25,000 /mm3 or the state of disease was stabilized for at least 4 weeks without treatment.
- Recognized as Intermediate-1, intermediate-2 or High according to International Prognostic Scoring System (IPSS).
- ≥4 weeks without treatment or the effect of previous treatment (antitumor effect) is considered to be discontinued after the end of previous therapy for MDS (including using erythropoiesis-stimulating agent, ESA) or other treatment with expectation of antitumor effect.
- Life expectancy is ≥3 months.
- ≥20 years of age (at the time of acquiring consent).
- Have score of 0 to 2 in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS).
With adequate function in major organs (heart, lungs, liver, kidneys, etc.).
- Aspartate aminotransferase (AST)(GOT): ≤3.0 times the upper boundary of the reference range at each institution
- Alanine aminotransferase (ALT)(GPT): ≤3.0 times the upper boundary of the reference range at each institution
- Total bilirubin: ≤1.5 times the upper boundary of the reference range at each institution
- Serum creatinine: ≤1.5 times the upper boundary of the reference range at each institution
- ECG: no abnormal findings requiring treatment
- Echocardiography: no abnormal findings requiring treatment
- Voluntarily sign the written informed consent form to participate in this study.
Exclusion criteria
Patients satisfying any of the following criteria will be excluded:
- With anemia (haemolytic anaemia, gastrointestinal haemorrhage, etc.) caused by factors other than MDS.
- With history or a complication of active malignant tumor (with the exception of target disease) within the past 1 year (basal cell carcinoma or squamous cell carcinoma of skin; or primary squamous cell carcinoma of the cervix or non-invasive breast cancer allows to be registered).
- Has received administration of granulocyte colony-stimulating factor (G-CSF) within 14 days before the examination for case registration.
- With an obvious infectious disease (including viral infections).
- With a serious complication (liver failure, renal failure, etc.).
- With a complication of serious heart disease (myocardial infarction, symptomatic ischemic heart disease, unstable angina, etc.). With history of arrhythmia within 2 years before registration or arrhythmia that requires treatment.
- With a serious gastrointestinal condition (severe or significant nausea/vomiting, diarrhea, etc.)
- Has tested positive for HBsAg or HIV antibody.
- With serious bleeding tendencies (disseminated intravascular coagulation (DIC), internal hemorrhage, etc.).
- With accumulation of pleural effusion/ascites that requires treatment such as paracentesis and ect.
- With hyponatremia (serum sodium is <130 mEq/L).
- Has undergone treatment of adrenocortical hormone (corresponding to >10 mg/24 hr of prednisolone conversion) for >2 weeks within 4 weeks before starting with administration of the study drug.
- Has undergone treatment of another investigational product or received chemotherapy, radiotherapy or immunotherapy that was under a clinical trial stage within 3 months before the case registration .
- Has not recovered from a surgery accompanying general anesthesia or received a surgery accompanying general anesthesia within 3 weeks before the case registration.
- With not properly controlled hypertension (systolic pressure ≧160 mmHg or diastolic pressure ≧110 mmHg).
- With not properly controlled epileptic seizure or with onset of epileptic seizure within 3 months before the case registration.
- Has undergone treatment with SyB 1101 in the past.
- With history of allergic reaction to polyethylene glycol,gelatin capsule or azacytidine.
- Difficult to participate in the study treatment due to psychiatric disorder, social condition, ect.
- With drug intoxication, narcotic addiction or alcohol dependency.
- Is pregnant, nursing or possibly pregnant.
- Is positive for pregnancy test (female patients) in the examination before the case registration.
- Not provided consent to the following contraceptive measures. Patients should avoid sexual intercourse with sexual partners or should use the contraceptive methods as described below in the following time periods: for male patients before case registration until 6 months after the end of administration of the study drug; for female patients with menstruation before case registration until the second menstrual period is confirmed after the end of administration; for menopausal women before case registration until 2 months after the end of administration.
(1) Male patients Must always use a condom. For effective contraception, it is recommended that contraceptive methods should also be applied by the female sexual partner and patient.
(2) Female patients Must use at least 1 of the following contraceptive methods. AT the same time, the male partner must use a condom.
- Oral contraceptive (birth control pill)
- Contraceptive injection
- Contraceptive patch
- Intrauterine device (IUD)
- Tubal ligation 24. Disqualified as a subject of study treatment judged by the principal investigator or investigator.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: SyB C-1101 and Azacytidine
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This study is a multi-center open-label study to assess the tolerability of oral administration of SyB C-1101 twice daily from Day 1 to Day 21 in combination with subcutaneous administration or intravenous drip infusion of azacitidine once daily at a dose of 75 mg/m2 (body surface) for 7 days during the period between Day 8 and Day 16, and to estimate the recommended dose (RD) of C-1101. SyB C-1101 will be administered at a daily dose of 560 mg or 840 mg in each of the 2 cohorts for a treatment period of 1 cycle for 28 days, including 21 days for SyB C-1101 treatment followed by 7 days of follow-up. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of dose-limiting toxicity (DLT) in patients administered with specified (level 1 or 2) dosage of SyB C-1101 in Cycle 1 and the descriptions of DLT
Time Frame: Up to 19 months
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Incidence rate of DLT and its binomial proportion confidence interval at the 90% level definition of DLT are as below: 1) Non-hematotoxicity of grade 3 or above with the exception of fever 2) fever of grade 2 or above uncontrolled by antipyretics |
Up to 19 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serious Adverse Events
Time Frame: Up to 19 months
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Up to 19 months
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Adverse Events, not including Serious Adverse Events
Time Frame: Up to 19 months
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Up to 19 months
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Change in laboratory values
Time Frame: Up to 19 months
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Up to 19 months
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Total efficacy in hematologic remission rate
Time Frame: Up to 19 months
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Ratio of patients scored as complete remission (CR), partial remission (PR) or marrow CR) according to the International Working Group (IWG) response criteria in myelodysplasia, 2006 (in each response criteria, responses must last at least 4 weeks): < CR>
Hgb ≥ 11 g/dL Platelets ≥ 100 × 109/L Neutrophils ≥ 1.0 × 109/L† Blasts 0% < PR > All CR criteria if abnormal before treatment except:
|
Up to 19 months
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Total efficacy in hematologic improvement rate
Time Frame: Up to 19 months
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Ratio of patients with hematologic improvement(erythroid, platelet or neutrophil) according to the International Working Group (IWG) response criteria in myelodysplasia, 2006 (in each response criteria, responses must last at least 8 weeks): < Erythroid response (pretreatment, <11 g/dL) >
< Platelet response (pretreatment, <100 × 109/L) >
< Neutrophil response (pretreatment, <1.0 × 109/L) > At least 100% increase and an absolute increase >0.5 × 109/L |
Up to 19 months
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Cytogenetic response rate
Time Frame: Up to 19 months
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Ratio of patients scored as complete cytogenetic response or partial cytogenetic response) according to the International Working Group (IWG) response criteria in myelodysplasia, 2006 (in each response criteria, responses must last at least 4 weeks): < Cytogenetic response > Complete: Disappearance of the chromosomal abnormality without appearance of new ones. Partial: At least 50% reduction of the chromosomal abnormality. |
Up to 19 months
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Peak plasma concentration (Cmax)
Time Frame: Up to 19 months
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Up to 19 months
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Time to maximum drug concentration time (tmax)
Time Frame: Up to 19 months
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Up to 19 months
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Area under the plasma concentration-time curve (AUC)
Time Frame: Up to 19 months
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Up to 19 months
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Elimination half-life (t1/2)
Time Frame: Up to 19 months
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Up to 19 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2015001
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Myelodysplastic Syndrome
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Brian JonasNational Cancer Institute (NCI); Celgene; Pharmacyclics LLC.CompletedPreviously Treated Myelodysplastic Syndrome | Myelodysplastic Syndrome | Therapy-Related Myelodysplastic Syndrome | Secondary Myelodysplastic Syndrome | Refractory High Risk Myelodysplastic SyndromeUnited States
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Thomas Jefferson UniversityAbbVieRecruitingMyelodysplastic Syndrome | Recurrent Myelodysplastic Syndrome | Refractory Myelodysplastic SyndromeUnited States
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Uma BorateRecruitingTherapy-Related Myelodysplastic Syndrome | Secondary Myelodysplastic SyndromeUnited States
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University Hospital, BrestRecruitingMyelodysplastic Syndromes | Myelodysplastic Syndrome With Isolated Del(5Q) | Myelodysplastic Syndrome With Del(5Q)France
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Cyclacel Pharmaceuticals, Inc.SuspendedLeukemia | Myelodysplastic Syndrome(MDS)United States
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TJ Biopharma Co., Ltd.Recruiting
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National Heart, Lung, and Blood Institute (NHLBI)National Cancer Institute (NCI)RecruitingMyelodysplastic Syndromes (MDS)United States, Israel
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AbbVieCelgene; Genentech, Inc.CompletedMyelodysplastic Syndromes (MDS)United States, Australia, Germany
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AbbVieGenentech, Inc.Active, not recruitingMyelodysplastic Syndromes (MDS)United States, Australia, Canada, France, Germany, Italy, United Kingdom
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The First Affiliated Hospital with Nanjing Medical...UnknownMyelodysplastic Syndromes (MDS)China
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