Study of SyB C-1101 in Patients With Myelodysplastic Syndrome

Myelodysplastic Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03495167
• Other study ID #: 2017001
• Status: Completed
• Phase: Phase 1
• Start date: October 6, 2017
• Est. completion date: May 28, 2019

Study information

• Verified date: November 2022
• Source: SymBio Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: May 28, 2019
• Est. primary completion date: May 28, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

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.

Locations

Country	Name	City	State
Japan	Research Site	Fukuoka
Japan	Research Site	Kobe	Hyogo
Japan	Research Site	Kumamoto
Japan	Research Site	Kurashiki	Okayama
Japan	Research Site	Kyoto
Japan	Research Site	Maebashi	Gunma
Japan	Research Site	Nagoya	Aichi
Japan	Research Site	Sapporo	Hokkaido
Japan	Research Site	Shinagawa	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
SymBio Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Severity of adverse events	Score as grade 1 to 5 according to criteria by CTCAE v4.0-JCOG.	Up to 2 years
Secondary	Relationship of adverse events to SyB C-1101	Score as "related " or "not related".	Up to 2 years
Secondary	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
Secondary	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
Secondary	Overall hematologic improvement rate	Calculate from the rate of patients with hematologic improvement according to IWG 2006 criteria.	Up to 2 years
Secondary	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
Secondary	Cmax	Maximum plasma concentration	Up to 2 years
Secondary	tmax	Time to maximum plasma concentration	Up to 2 years
Secondary	AUC	Area under the plasma concentration curve	Up to 2 years
Secondary	t 1/2	Half-life time	Up to 2 years