Study of SyB C-1101 in Patients With Myelodysplastic Syndrome

Multi-center, Open-label, Phase I Study of SyB C-1101 in Patients With Myelodysplastic Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: SyB C-1101

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Research Site
  • Kumamoto, Japan
    • Research Site
  • Kyoto, Japan
    • Research Site
  • Aichi
    • Nagoya, Aichi, Japan
      • Research Site
  • Gunma
    • Maebashi, Gunma, Japan
      • Research Site
  • Hokkaido
    • Sapporo, Hokkaido, Japan
      • Research Site
  • Hyogo
    • Kobe, Hyogo, Japan
      • Research Site
  • Okayama
    • Kurashiki, Okayama, Japan
      • Research Site
  • Tokyo
    • Shinagawa, Tokyo, Japan
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Calculate from the rate between number of patients occurred AE and number of patients received SyB C-1101.	Up to 2 years
Severity of adverse events	Score as grade 1 to 5 according to criteria by CTCAE v4.0-JCOG.	Up to 2 years
Relationship of adverse events to SyB C-1101	Score as "related " or "not related".	Up to 2 years
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.)	Up to 2 years
Overall hematologic response rate	Calculate from the rate of patients scored as CR, PR or marrow CR according to IWG 2006 criteria.	Up to 2 years
Overall hematologic improvement rate	Calculate from the rate of patients with hematologic improvement according to IWG 2006 criteria.	Up to 2 years
Overall cytogenetic response rate	Calculate from the rate of patients scored as complete cytogeneic response or partial cytogenetic response according to IWG 2006 criteria.	Up to 2 years
Cmax	Maximum plasma concentration	Up to 2 years
tmax	Time to maximum plasma concentration	Up to 2 years
AUC	Area under the plasma concentration curve	Up to 2 years
t 1/2	Half-life time	Up to 2 years

Collaborators and Investigators

• Sponsor: SymBio Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 6, 2017
• Primary Completion (ACTUAL): May 28, 2019
• Study Completion (ACTUAL): May 28, 2019

Study Registration Dates

• First Submitted: November 17, 2017
• First Submitted That Met QC Criteria: April 4, 2018
• First Posted (ACTUAL): April 11, 2018

Study Record Updates

• Last Update Posted (ACTUAL): November 16, 2022
• Last Update Submitted That Met QC Criteria: November 14, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: 2017001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No