Combination Therapy of SyB C-1101 and Azacytidine in Patients With Myelodysplastic Syndrome
- Conditions
- Myelodysplastic Syndrome
- Interventions
- Drug: SyB C-1101 and Azacytidine
- Registration Number
- NCT02783547
- Lead Sponsor
- SymBio Pharmaceuticals
- Brief Summary
This is a Phase 1 clinical trial to evaluate the tolerability of a combination therapy of SyB C-1101 (rigosertib sodium) and Azacytidine and to determine the recommended dose of SyB C-1101for Phase 2 trial in patients with myelodysplastic syndrome.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SyB C-1101 and Azacytidine SyB C-1101 and Azacytidine -
- Primary Outcome Measures
Name Time Method 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 Up to 19 months 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
- Secondary Outcome Measures
Name Time Method Serious Adverse Events Up to 19 months Adverse Events, not including Serious Adverse Events Up to 19 months Change in laboratory values Up to 19 months Total efficacy in hematologic remission rate Up to 19 months 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\>
* Bone marrow: ≤5% myeloblasts with normal maturation of all cell lines.
* Persistent dysplasia will be noted.
* Peripheral blood:
Hgb ≥ 11 g/dL Platelets ≥ 100 × 109/L Neutrophils ≥ 1.0 × 109/L† Blasts 0% \< PR \>
All CR criteria if abnormal before treatment except:
* Bone marrow blasts decreased by ≥ 50% over pretreatment but still \> 5%
* Cellularity and morphology not relevant \<marrow CR\>
* Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment
* Peripheral blood: if hematological improvement (HI) responses, they will be noted in addition to marrow CR.Total efficacy in hematologic improvement rate Up to 19 months 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) \>
1. Hgb increase by ≥1.5 g/dL.
2. Relevant reduction of units of red blood cell (RBC) transfusions by an absolute number of at least 4 RBC transfusions/8 wk compared with the pretreatment transfusion number in the previous 8 wk. Only RBC transfusions given for a Hgb of ≤9.0 g/dL pretreatment will count in the RBC transfusion response evaluation.
\< Platelet response (pretreatment, \<100 × 109/L) \>
1. Absolute increase of ≥30 × 109/L for patients starting with \>20 × 109/L platelets
2. Increase from \<20 × 109/L to \>20 × 109/L and by at least 100%
\< Neutrophil response (pretreatment, \<1.0 × 109/L) \> At least 100% increase and an absolute increase \>0.5 × 109/LCytogenetic response rate Up to 19 months 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.Peak plasma concentration (Cmax) Up to 19 months Time to maximum drug concentration time (tmax) Up to 19 months Area under the plasma concentration-time curve (AUC) Up to 19 months Elimination half-life (t1/2) Up to 19 months
Trial Locations
- Locations (1)
Research Site
🇯🇵Shinagawa, Tokyo, Japan