search
Back to results

Study of SyB C-1101 in Patients With Myelodysplastic Syndrome

Primary Purpose

Myelodysplastic Syndrome

Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
SyB C-1101
Sponsored by
SymBio Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Patients who meet all of the following criteria are eligible for enrollment in the study:

  1. 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.
  2. Classified as Intermediate-1, Intermediate-2 or High-risk, according to IPSS classification.

  3. 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:

    • Patients who failed to achieve complete remission, partial remission, or hematologic improvement*
    • Patients experienced with recurrence/relapse after achieving complete remission, partial remission, or hematologic improvement*
    • 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)
  4. 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.
  5. Patients with expected survival of ≥3 months.
  6. Patients aged 20 years or older (at the time of informed consent).
  7. ECOG Performance Status (PS) of 0, 1 or 2

  8. Patients with adequate major organ functions (including the heart, lungs, liver, and kidneys).

    • AST (GOT): ≤2.5 -fold the upper limit of normal range at each institution
    • ALT (GPT) : ≤2.5 -fold the upper limit of normal range at each institution
    • Total bilirubin: <2.0 mg/dL (except patients with Gilbert's disease or hemolysis)
    • Serum creatinine: <2.0 mg/dL
    • ECG: Absence of abnormal findings that require treatment
    • Echocardiography: Absence of abnormal findings that require treatment
  9. 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.

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SyB C-1101

Arm Description

Outcomes

Primary Outcome Measures

Identification of Dose-Limiting Toxicity (DLT) and Number of Patients with DLT in Each Cohort
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
Calculate from the rate between number of patients occurred AE and number of patients received SyB C-1101.
Severity of adverse events
Score as grade 1 to 5 according to criteria by CTCAE v4.0-JCOG.
Relationship of adverse events to SyB C-1101
Score as "related " or "not related".
Change of laboratory test values
Number of patients with changes in laboratory values OR list each lab value separately (e.g.Hgb, Fe, Hct, etc.)
Overall hematologic response rate
Calculate from the rate of patients scored as CR, PR or marrow CR according to IWG 2006 criteria.
Overall hematologic improvement rate
Calculate from the rate of patients with hematologic improvement according to IWG 2006 criteria.
Overall cytogenetic response rate
Calculate from the rate of patients scored as complete cytogeneic response or partial cytogenetic response according to IWG 2006 criteria.
Cmax
Maximum plasma concentration
tmax
Time to maximum plasma concentration
AUC
Area under the plasma concentration curve
t 1/2
Half-life time

Full Information

First Posted
November 17, 2017
Last Updated
November 14, 2022
Sponsor
SymBio Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT03495167
Brief Title
Study of SyB C-1101 in Patients With Myelodysplastic Syndrome
Official Title
Multi-center, Open-label, Phase I Study of SyB C-1101 in Patients With Myelodysplastic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Completed
Study Start Date
October 6, 2017 (Actual)
Primary Completion Date
May 28, 2019 (Actual)
Study Completion Date
May 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SymBio Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SyB C-1101
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
SyB C-1101
Intervention Description
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.
Primary Outcome Measure Information:
Title
Identification of Dose-Limiting Toxicity (DLT) and Number of Patients with DLT in Each Cohort
Description
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.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Incidence of adverse events
Description
Calculate from the rate between number of patients occurred AE and number of patients received SyB C-1101.
Time Frame
Up to 2 years
Title
Severity of adverse events
Description
Score as grade 1 to 5 according to criteria by CTCAE v4.0-JCOG.
Time Frame
Up to 2 years
Title
Relationship of adverse events to SyB C-1101
Description
Score as "related " or "not related".
Time Frame
Up to 2 years
Title
Change of laboratory test values
Description
Number of patients with changes in laboratory values OR list each lab value separately (e.g.Hgb, Fe, Hct, etc.)
Time Frame
Up to 2 years
Title
Overall hematologic response rate
Description
Calculate from the rate of patients scored as CR, PR or marrow CR according to IWG 2006 criteria.
Time Frame
Up to 2 years
Title
Overall hematologic improvement rate
Description
Calculate from the rate of patients with hematologic improvement according to IWG 2006 criteria.
Time Frame
Up to 2 years
Title
Overall cytogenetic response rate
Description
Calculate from the rate of patients scored as complete cytogeneic response or partial cytogenetic response according to IWG 2006 criteria.
Time Frame
Up to 2 years
Title
Cmax
Description
Maximum plasma concentration
Time Frame
Up to 2 years
Title
tmax
Description
Time to maximum plasma concentration
Time Frame
Up to 2 years
Title
AUC
Description
Area under the plasma concentration curve
Time Frame
Up to 2 years
Title
t 1/2
Description
Half-life time
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Patients who meet all of the following criteria are eligible for enrollment in the study: 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. Classified as Intermediate-1, Intermediate-2 or High-risk, according to IPSS classification. 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: Patients who failed to achieve complete remission, partial remission, or hematologic improvement* Patients experienced with recurrence/relapse after achieving complete remission, partial remission, or hematologic improvement* 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) 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. Patients with expected survival of ≥3 months. Patients aged 20 years or older (at the time of informed consent). ECOG Performance Status (PS) of 0, 1 or 2 Patients with adequate major organ functions (including the heart, lungs, liver, and kidneys). AST (GOT): ≤2.5 -fold the upper limit of normal range at each institution ALT (GPT) : ≤2.5 -fold the upper limit of normal range at each institution Total bilirubin: <2.0 mg/dL (except patients with Gilbert's disease or hemolysis) Serum creatinine: <2.0 mg/dL ECG: Absence of abnormal findings that require treatment 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katsuhisa Goto
Organizational Affiliation
SymBio Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Nagoya
State/Province
Aichi
Country
Japan
Facility Name
Research Site
City
Maebashi
State/Province
Gunma
Country
Japan
Facility Name
Research Site
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Research Site
City
Kobe
State/Province
Hyogo
Country
Japan
Facility Name
Research Site
City
Kurashiki
State/Province
Okayama
Country
Japan
Facility Name
Research Site
City
Shinagawa
State/Province
Tokyo
Country
Japan
Facility Name
Research Site
City
Fukuoka
Country
Japan
Facility Name
Research Site
City
Kumamoto
Country
Japan
Facility Name
Research Site
City
Kyoto
Country
Japan

12. IPD Sharing Statement

Learn more about this trial

Study of SyB C-1101 in Patients With Myelodysplastic Syndrome

We'll reach out to this number within 24 hrs