The purpose of this study is to investigate tolerability when SyB C-1101 is orally administered twice daily for 14 consecutive days to the patients with recurrent/relapsed or refractory myelodysplastic syndrome, to determine the dose-limiting toxicity and maximum tolerated dose, and to estimate the recommended dose for phase II studies. Pharmacokinetics and antitumor effects will also be investigated.
In Cohort 1, SyB C-1101 280 mg/dose group, Participants will be administered 280 mg/dose of SyB C-1101 twice daily orally for 14 consecutive days, followed by 7-day observation period. In Cohort 2, SyB C-1101 560 mg/dose group, Participants will be administered 560 mg/dose of SyB C-1101 twice daily orally for 14 consecutive days, followed by 7-day observation period. In both Cohorts, the treatment period of 21 days constitutes 1 cycle, and the treatment was allowed for up to cycles. The participants received SyB C-1101 only once daily on Day 1 and Day 14 of Cycle 1 for the investigation of the pharmacokinetics.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
10
SyB C-1101（rigosertib sodium） will be administered to two cohorts at either 280 mg/day or 560 mg/day. The dose will be administered orally twice daily for 14 consecutive days, followed by 7-day observation period. The treatment period of 21 days (14 days of administration + 7 days of observation) constitutes 1 cycle. The study will involve treatment through the second cycle, but treatment can be continued for 3 or more cycles if conditions for continued administration are satisfied. However, treatment will be limited to a maximum of 6 cycles including the first cycle.
Research site
Nagoya, Aichi-ken, Japan
Research site
Isehara, Kanagawa, Japan
Research site
Sendai, Miyagi, Japan
Research site
Kyoto, Japan
Adverse Events
Total Number Affected by Any Adverse Event (Details are presented in Adverse Event section)
Time frame: Up to 18 weeks
Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)
A DLT was defined as adverse events for which a causal relationship with the investigational drug could not be ruled out and which met the following criteria that occurred by the final observation in Cycle 1. DLTs were also assessed in the Efficacy and Safety Assessment Committee. Criteria 1. Grade 3 or higher non-hematologic toxicity. However, nausea, vomiting, diarrhoea, pyrexia, stomatitis, and esophagitis/dysphagia are excluded (Grade 3 nausea, vomiting, diarrhoea, and pyrexia that cannot be controlled with antiemetic, antidiarrheal, or antifebrile agents are regarded as DLTs) 2. Grade 3 or higher stomatitis, esophagitis, and dysphagia that persist for \>= 4 days
Time frame: Up to 21 days
Hematologic Remission Effect (IWG 2006 Criteria, Responses Sustained >= 4 Weeks)
Definition Complete remission (CR) Bone marrow: \<= 5% myeloblasts; normal maturation of all cell lines Peripheral blood: Hemoglobin (Hgb) \>= 11 g/dL, Platelets \>= 100×10\^9/L, Neutrophils \>= 1.0×10\^9/L, Blasts 0% Partial remission (PR) Same as CR except bone marrow blasts decreased by \>= 50% over pretreatment but still \> 5% Marrow CR Bone marrow: \<= 5% myeloblasts and decrease by \>= 50% over pretreatment Peripheral blood: will be noted in addition to marrow CR Stable disease Failure to achieve at least PR, but no evidence of progression for \> 8 weeks Disease progression Patients with: Less than 5% blasts: \>= 50% increase in blasts to \> 5% blasts 5%-10% blasts: \>= 50% increase to \> 10% blasts 10%-20% blasts: \>= 50% increase to \> 20% blasts 20%-30% blasts: \>= 50% increase to \> 30% blasts Any of the following: At least 50% decrement from maximum remission/response in granulocytes or platelets Reduction in Hgb by \>= 2 g/dL Transfusion dependence
Time frame: Up to 60 weeks
Hematologic Improvement Effect (IWG 2006 Criteria, Responses Must Last at Least 8 Weeks)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Definition Hematologic Improvement Erythrocyte (HI-E): Hgb increase by \>= 1.5 g/dL Relevant reduction of units of red blood cell (RBC) transfusions by an absolute number of at least 4 RBC transfusions/8 week compared with the pretreatment transfusion number in the previous 8 week. Only RBC transfusions given for a Hgb of \<= 9.0 g/dL pretreatment will count in the RBC transfusion response evaluation Hematologic Improvement Platelet (HI-P): Absolute increase of \>= 30×10\^9/L for patients starting with \> 20×10\^9/L platelets Increase from \< 20×10\^9/L to \> 20×10\^9/L and by at least 100% Hematologic Improvement Neutrophil (HI-N): At least 100% increase and an absolute increase \> 0.5×10\^9/L Progressive disease / Relapse: At least 1 of the following: At least 50% decrement from maximum response levels in granulocytes or platelets Reduction in Hgb by \>= 1.5 g/dL Transfusion dependence
Time frame: Up to 18 weeks