Study of SyB C-1101 in Patients With Myelodysplastic Syndrome
Study Details
Study Description
Brief Summary
To assess tolerability of SyB C-1101 when administered orally BID for 21 days followed by a 7-day observation period in patients with recurrent/relapsed or refractory myelodysplastic syndrome in order to determine a recommended dose (RD). To assess safety, efficacy and pharmacokinetics.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SyB C-1101
|
Drug: SyB C-1101
SyB C-1101 (rigosertib sodium) will be administered to two cohorts of patients; each receives either twice daily (560 mg before breakfast and 560 mg before dinner) or twice daily (840 mg before breakfast and 280 mg before dinner. SyB C-1101 will be administered orally twice daily for 21 consecutive days, followed by a 7-day observation period. The treatment period of 28 days (21 days of administration + 7 days of observation) constitutes 1 cycle.
|
Outcome Measures
Primary Outcome Measures
- Identification of Dose-Limiting Toxicity (DLT) and Number of Patients with DLT in Each Cohort [Up to 2 years]
Based on the number of patients with DLT and administration dose in each cohort, recommended dosage will be defined for the following clinical phase. A DLT is defined as an adverse event that occurred during the Cycle 1, for which a causality with the investigational products (IP) cannot be ruled out and meets the following criteria. Criteria: ≥ Grade3 non-hematological toxicity (except pyrexia). However nausea, vomiting, diarrhea, stomatitis and esophagitis/dysphagia are excluded (≥ Grade 3 nausea, vomiting, and diarrhea persist for ≥ 48 hours and uncontrolled by antiemetic or antidiarrheal agents, and ≥ Grade 3 stomatitis and esophagitis/dysphagia lasting for ≥ 4 days are regarded as DLTs). ≥ Grade 2 pyrexia uncontrolled by antipyretic agents. However, in case pyrexia of ˃ 39°C occurred within 24 hours after administration of SyB C-1101 and its cause is unclear, it is deemed that the causality to the IP cannot be ruled out.
Secondary Outcome Measures
- Incidence of adverse events [Up to 2 years]
Calculate from the rate between number of patients occurred AE and number of patients received SyB C-1101.
- Severity of adverse events [Up to 2 years]
Score as grade 1 to 5 according to criteria by CTCAE v4.0-JCOG.
- Relationship of adverse events to SyB C-1101 [Up to 2 years]
Score as "related " or "not related".
- Change of laboratory test values [Up to 2 years]
Number of patients with changes in laboratory values OR list each lab value separately (e.g.Hgb, Fe, Hct, etc.)
- Overall hematologic response rate [Up to 2 years]
Calculate from the rate of patients scored as CR, PR or marrow CR according to IWG 2006 criteria.
- Overall hematologic improvement rate [Up to 2 years]
Calculate from the rate of patients with hematologic improvement according to IWG 2006 criteria.
- Overall cytogenetic response rate [Up to 2 years]
Calculate from the rate of patients scored as complete cytogeneic response or partial cytogenetic response according to IWG 2006 criteria.
- Cmax [Up to 2 years]
Maximum plasma concentration
- tmax [Up to 2 years]
Time to maximum plasma concentration
- AUC [Up to 2 years]
Area under the plasma concentration curve
- t 1/2 [Up to 2 years]
Half-life time
Eligibility Criteria
Criteria
Patients who meet all of the following criteria are eligible for enrollment in the study:
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Histologically or cytologically diagnosed as myelodysplastic syndrome (MDS) according to WHO criteria or FAB classification. For patients with RAEB in transformation (RAEB-t), peripheral WBC is ≦25,000 /mm3 and the disease is stable for at least 4 weeks.
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Classified as Intermediate-1, Intermediate-2 or High-risk, according to IPSS classification.
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Patients with a history of previous treatment of the target disease (e.g., immunosuppressive therapy, protein anabolic steroids, and chemotherapy including azacitidine and lenalidomide) and meet one of the followings:
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Patients who failed to achieve complete remission, partial remission, or hematologic improvement*
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Patients experienced with recurrence/relapse after achieving complete remission, partial remission, or hematologic improvement*
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Patients who were intolerable to the previous therapy *: The most recent assessment of the therapeutic effect based on "Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia" (IWG2006 criteria)
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Off all other treatment (including erythropoiesis stimulating agents) for MDS, for at least 4 weeks prior to enrollment and no carry-over (of antitumor effect) from previous treatment is expected as judged by Investigator. Transfusion is allowed, as clinically indicated.
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Patients with expected survival of ≥3 months.
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Patients aged 20 years or older (at the time of informed consent).
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ECOG Performance Status (PS) of 0, 1 or 2
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Patients with adequate major organ functions (including the heart, lungs, liver, and kidneys).
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AST (GOT): ≤2.5 -fold the upper limit of normal range at each institution
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ALT (GPT) : ≤2.5 -fold the upper limit of normal range at each institution
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Total bilirubin: <2.0 mg/dL (except patients with Gilbert's disease or hemolysis)
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Serum creatinine: <2.0 mg/dL
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ECG: Absence of abnormal findings that require treatment
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Echocardiography: Absence of abnormal findings that require treatment
- The patient must sign an informed consent form indicating that s/he understands the purpose of and procedure required for the study and is willing to participate in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Nagoya | Aichi | Japan | |
| 2 | Research Site | Maebashi | Gunma | Japan | |
| 3 | Research Site | Sapporo | Hokkaido | Japan | |
| 4 | Research Site | Kobe | Hyogo | Japan | |
| 5 | Research Site | Kurashiki | Okayama | Japan | |
| 6 | Research Site | Shinagawa | Tokyo | Japan | |
| 7 | Research Site | Fukuoka | Japan | ||
| 8 | Research Site | Kumamoto | Japan | ||
| 9 | Research Site | Kyoto | Japan |
Sponsors and Collaborators
- SymBio Pharmaceuticals
Investigators
- Study Director: Katsuhisa Goto, SymBio Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2017001