Safety and Pharmacokinetics Study of SyB L-1101 in Patients With Recurrent/Relapsed or Refractory Myelodysplastic Syndrome (MDS)
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Clinical Trial of SyB L-1101 in Patients With Myelodysplastic Syndrome|
- Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: Yes ]
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 2. DLTs were also to be assessed in the Efficacy and Safety Assessment Committee.
- Grade 3 or higher non-hematologic toxicity. However, nausea, vomiting, diarrhea, pyrexia, stomatitis, and esophagitis/dysphagia are excluded (Grade 3 nausea, vomiting, diarrhea, and pyrexia that cannot be controlled with antiemetic, antidiarrheal, or antifebrile agents are regarded as DLTs)
- Grade 3 or higher stomatitis, esophagitis, and dysphagia that persist for >= 4 days
- Hematologic Remission Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 4 Weeks) [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
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 criteria 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 wks
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
- Hematologic Improvement Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 8 Weeks) [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: No ]
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
- Maximum Tolerated Dose (MTD) [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: Yes ]MTD was investigated with an index of DLT
|Study Start Date:||June 2012|
|Study Completion Date:||February 2015|
|Primary Completion Date:||February 2015 (Final data collection date for primary outcome measure)|
Experimental: SyB L-1101
In Cohort 1, SyB L-1101 1200 mg/day group, Participants were administered 1200 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.
In Cohort 2, SyB L-1101 1800 mg/day group, Participants were administered 1800 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period.
For both Cohorts, the treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.
Drug: SyB L-1101
SyB L-1101（rigosertib sodium） will be administered to two cohorts at either 1200 mg/day or 1800 mg/day.
The dose will be administered intravenously for 72 continuous hours (3 days), followed by 11-day observation period. The treatment period of 14 days (3 days of administration + 11 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01700335
|Nagoya, Aichi, Japan|