Combination Therapy of SyB C-1101 and Azacytidine in Patients With Myelodysplastic Syndrome

NCT02783547 | Withdrawn Phase 1

• 1 other identifier: 2015001
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

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.

Conditions

Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• 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

  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

  Up to 19 months

Secondary Outcomes (10)

• 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

• Total efficacy in hematologic improvement rate

  Up to 19 months

Study Arms (1)

SyB C-1101 and Azacytidine

EXPERIMENTAL

Drug: SyB C-1101 and Azacytidine

Interventions

SyB C-1101 and Azacytidine DRUG

This study is a multi-center open-label study to assess the tolerability of oral administration of SyB C-1101 twice daily from Day 1 to Day 21 in combination with subcutaneous administration or intravenous drip infusion of azacitidine once daily at a dose of 75 mg/m2 (body surface) for 7 days during the period between Day 8 and Day 16, and to estimate the recommended dose (RD) of C-1101. SyB C-1101 will be administered at a daily dose of 560 mg or 840 mg in each of the 2 cohorts for a treatment period of 1 cycle for 28 days, including 21 days for SyB C-1101 treatment followed by 7 days of follow-up.

SyB C-1101 and Azacytidine

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients satisfying all the following criteria will be included:
• Histologically or cytologically diagnosed with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) according to World Health Organization (WHO) Classification or French-American-British (FAB) Classification. As for patients with refractory anemia with excess of blasts in transformation (RAEB-t), however, the peripheral blood white blood cell count is ≤ 25,000 /mm3 or the state of disease was stabilized for at least 4 weeks without treatment.
• Recognized as Intermediate-1, intermediate-2 or High according to International Prognostic Scoring System (IPSS).
• ≥4 weeks without treatment or the effect of previous treatment (antitumor effect) is considered to be discontinued after the end of previous therapy for MDS (including using erythropoiesis-stimulating agent, ESA) or other treatment with expectation of antitumor effect.
• Life expectancy is ≥3 months.
• ≥20 years of age (at the time of acquiring consent).
• Have score of 0 to 2 in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS).
• With adequate function in major organs (heart, lungs, liver, kidneys, etc.).
• Aspartate aminotransferase (AST)(GOT): ≤3.0 times the upper boundary of the reference range at each institution
• Alanine aminotransferase (ALT)(GPT): ≤3.0 times the upper boundary of the reference range at each institution
• Total bilirubin: ≤1.5 times the upper boundary of the reference range at each institution
• Serum creatinine: ≤1.5 times the upper boundary of the reference range at each institution
• ECG: no abnormal findings requiring treatment
• Echocardiography: no abnormal findings requiring treatment
• Voluntarily sign the written informed consent form to participate in this study.

You may not qualify if:

• Patients satisfying any of the following criteria will be excluded:
• With anemia (haemolytic anaemia, gastrointestinal haemorrhage, etc.) caused by factors other than MDS.
• With history or a complication of active malignant tumor (with the exception of target disease) within the past 1 year (basal cell carcinoma or squamous cell carcinoma of skin; or primary squamous cell carcinoma of the cervix or non-invasive breast cancer allows to be registered).
• Has received administration of granulocyte colony-stimulating factor (G-CSF) within 14 days before the examination for case registration.
• With an obvious infectious disease (including viral infections).
• With a serious complication (liver failure, renal failure, etc.).
• With a complication of serious heart disease (myocardial infarction, symptomatic ischemic heart disease, unstable angina, etc.). With history of arrhythmia within 2 years before registration or arrhythmia that requires treatment.
• With a serious gastrointestinal condition (severe or significant nausea/vomiting, diarrhea, etc.)
• Has tested positive for HBsAg or HIV antibody.
• With serious bleeding tendencies (disseminated intravascular coagulation (DIC), internal hemorrhage, etc.).
• With accumulation of pleural effusion/ascites that requires treatment such as paracentesis and ect.
• With hyponatremia (serum sodium is \<130 mEq/L).
• Has undergone treatment of adrenocortical hormone (corresponding to \>10 mg/24 hr of prednisolone conversion) for \>2 weeks within 4 weeks before starting with administration of the study drug.
• Has undergone treatment of another investigational product or received chemotherapy, radiotherapy or immunotherapy that was under a clinical trial stage within 3 months before the case registration .
• Has not recovered from a surgery accompanying general anesthesia or received a surgery accompanying general anesthesia within 3 weeks before the case registration.

Sponsors & Collaborators

• SymBio Pharmaceuticals: lead

Study Sites (4)

Research Site

Nagoya, Aichi-ken, Japan

Location

Research Site

Kakamigahara, Gifu, Japan

Location

Research Site

Sendai, Miyagi, Japan

Location

Research Site

Shinagawa, Tokyo, Japan

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Katsuhisa Goto

  SymBio Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2016
• First Posted: May 26, 2016
• Study Start: December 1, 2015
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: November 17, 2022

Record last verified: 2022-11

Locations

JP (4)