Safety and Pharmacokinetics Study of SyB L-1101 in Patients With Recurrent/Relapsed or Refractory Myelodysplastic Syndrome (MDS)

NCT01700335 | Completed Phase 1 Results

• 1 other identifier: 2011005
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to investigate tolerability when SyB L-1101 is administered intravenously in patients with recurrent/relapsed or refractory myelodysplastic syndrome, to determine the dose-limiting toxicity and maximum tolerated dose, and to estimate the recommended dose for phase II studies. Pharmacokinetics and antitumor effects will also be investigated.

Conditions

Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)

  A DLT was defined as adverse events for which a causal relationship with the investigational drug could not be ruled out and which met the following criteria that occurred by the final observation in Cycle 2. DLTs were also to be assessed in the Efficacy and Safety Assessment Committee. Criteria: 1. Grade 3 or higher non-hematologic toxicity. However, nausea, vomiting, diarrhea, pyrexia, stomatitis, and esophagitis/dysphagia are excluded (Grade 3 nausea, vomiting, diarrhea, and pyrexia that cannot be controlled with antiemetic, antidiarrheal, or antifebrile agents are regarded as DLTs) 2. Grade 3 or higher stomatitis, esophagitis, and dysphagia that persist for \>= 4 days

  Up to 60 weeks

Secondary Outcomes (2)

• Hematologic Remission Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 4 Weeks)

  Up to 60 weeks

• Hematologic Improvement Effect (IWG 2006 Criteria, Responses Must be Sustained at Least 8 Weeks)

  Up to 60 weeks

Other Outcomes (1)

• Maximum Tolerated Dose (MTD)

  Up to 16 weeks

Study Arms (1)

SyB L-1101

EXPERIMENTAL

In Cohort 1, SyB L-1101 1200 mg/day group, Participants were administered 1200 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period. In Cohort 2, SyB L-1101 1800 mg/day group, Participants were administered 1800 mg/day of SyB L-1101 intravenously for 3 consecutive days, followed by 11-day observation period. For both Cohorts, the treatment period of 14 days constitutes 1 cycle, and the treatment was allowed for up to 8 cycles.

Drug: SyB L-1101

Interventions

SyB L-1101 DRUG

SyB L-1101（rigosertib sodium） will be administered to two cohorts at either 1200 mg/day or 1800 mg/day. The dose will be administered intravenously for 72 continuous hours (3 days), followed by 11-day observation period. The treatment period of 14 days (3 days of administration + 11 days of observation) constitutes 1 cycle. The study will involve treatment through the second cycle, but treatment can be continued for 3 or more cycles if conditions for continued administration are satisfied.

SyB L-1101

Eligibility Criteria

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

You may qualify if:

• \- Patients must satisfy the following conditions listed below.
• Patients who have been histologically documented or cytologically confirmed with myelodysplastic syndrome (MDS), and who have been found to meet any of the following criteria on the basis of the World Health Organization (WHO) classification or French-American-British (FAB) classification.
• Refractory Anemia (RA) (\< 5% myeloblasts, \< 15% ringed sideroblasts)
• RA with Ring Sideroblasts (RARS) (\< 5% myeloblasts, \>= 15% ringed sideroblasts)
• RA with Excess of Blasts (RAEB)-1 (5% to 9% myeloblasts)
• RAEB-2 (10% to 19% myeloblasts)
• RAEB in transformation (RAEB-t) (20% to 29% myeloblasts or \< 25,000/mm\^3 peripheral leukocytes)
• Chronic myelomonocytic leukemia (CMML) (10% to 19% myeloblasts in marrow, \>= 1,000/mm\^3 peripheral monocytes, \< 13,000/mm\^3 leukocytes) However, RA patients must have score of Int-2 or higher in International prognostic scoring system (IPSS).
• Patients with a low value in at least one blood cell lineage (having at least one of the following cytopenias).
• Neutrophils : \< 1,800/mm\^3
• Platelets : \< 100,000/mm\^3
• Hemoglobin : \< 10 g/dL
• Patients with a previous history of chemotherapy (including lenalidomide) for the target disease who meet any of the following criteria.
• Patients who have not achieved complete remission, partial remission, or hematologic improvement\*
• Patients with recurrence/relapse after complete remission, partial remission, or hematologic improvement\*

You may not qualify if:

• \- Patients who satisfy any of the following conditions will not be enrolled in the study.
• Patients with anemia caused by factors other than MDS (hemolytic anemia, gastrointestinal (GI) bleeding, etc.).
• Patients who have undergone treatment for an active malignant tumor within the past year (except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast).
• Patients who have been administered a cytokine preparation such as granulocyte-colony stimulating factor (G-CSF), erythropoietin, etc. within 14 days of tests for enrollment of the study.
• Patients with obvious infectious diseases (including viral infections).
• Patients with serious complications (liver failure, renal failure, etc.).
• Patients with a complicating or previous history of serious heart disease (myocardial infarction, ischemic heart disease, etc.) within the past two years before enrollment, and with cardiac arrhythmia requiring treatment.
• Patients with a serious gastrointestinal condition (severe or significant nausea/vomiting, diarrhea, etc.).
• Patients who are positive for the Hepatitis B surface (HBs) antigen or HIV antibodies.
• Patients with serious bleeding tendencies (disseminated intravascular coagulation (DIC), internal hemorrhage, etc.).
• Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of \<130 mEq/L).
• Patients who have been administered a drug in a clinical trial or an unapproved drug within three months before enrollment.
• Patients with an addiction to a legal or illegal drug, or with alcohol dependency.
• Patients who are pregnant or may become pregnant.
• Patients who have not consented to the following contraceptive measures.

Sponsors & Collaborators

• SymBio Pharmaceuticals: lead

Study Sites (3)

Research Site

Nagoya, Aichi-ken, Japan

Location

Research Site

Fukuoka, Japan

Location

Research Site

Tokyo, Japan

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Director of Clinical Trials
• Organization: SymBio Pharmaceuticals

kgoto.34@symbiopharma.com

+81-3-5472-1127

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: August 7, 2012
• First Posted: October 4, 2012
• Study Start: June 1, 2012
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: November 21, 2022
• Results First Posted: September 14, 2016

Record last verified: 2022-10

Locations

JP (3)