Safety and Pharmacokinetics Study of SyB L-1101 in Patients With Recurrent/Relapsed or Refractory Myelodysplastic Syndrome (MDS)
Verified October 2012 by SymBio Pharmaceuticals
Information provided by (Responsible Party):
First received: August 7, 2012
Last updated: October 1, 2012
Last verified: October 2012
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.
Drug: SyB L-1101
||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Phase I Clinical Trial of SyB L-1101 in Patients With Myelodysplastic Syndrome
Primary Outcome Measures:
Secondary Outcome Measures:
- Safety (adverse events) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
Safety (type, frequency, severity, reversibility)
- Safety (changes in clinical laboratory test results) [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
Safety (clinical laboratory test results and abnormal clinical laboratory test results throughout the study)
- Efficacy (total efficacy in hematologic remission ratio) [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: Yes ]
Hematologic remission ratio (ratio of patients scored as CR, PR, or marrow CR)
- Efficacy (total efficacy in hematologic improvement ratio) [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: Yes ]
Hematologic improvement ratio (ratio of patients scored as hematologically improved "erythrocyte lineage, platelet lineage, or neutrophil lineage")
- Efficacy (cytogenetic response ratio) [ Time Frame: Up to 60 weeks ] [ Designated as safety issue: Yes ]
Cytogenetic response ratio (ratio of patients scored as complete cytogenetic response or partial cytogenetic response)
- Pharmacokinetics (Cmax) [ Time Frame: 0, 1, 3, 6, 24, 48, 72 hours after the start of IV infusion, and 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72 hours after the end of IV infusion ] [ Designated as safety issue: No ]
Maximum concentration in plasma (Cmax)
- Pharmacokinetics (tmax) [ Time Frame: 0, 1, 3, 6, 24, 48, 72 hours after the start of IV infusion, and 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72 hours after the end of IV infusion ] [ Designated as safety issue: No ]
Time to maximum plasma concentration (tmax)
- Pharmacokinetics (AUC) [ Time Frame: 0, 1, 3, 6, 24, 48, 72 hours after the start of IV infusion, and 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72 hours after the end of IV infusion ] [ Designated as safety issue: No ]
Area under the plasma concentration curve (AUC)
- Pharmacokinetics (t1/2) [ Time Frame: 0, 1, 3, 6, 24, 48, 72 hours after the start of IV infusion, and 0.25, 0.5, 1, 2, 4, 8, 24, 48, 72 hours after the end of IV infusion ] [ Designated as safety issue: No ]
Elimination half-life (t1/2)
- Pharmacokinetics (urinary excretion rate) [ Time Frame: 0 to 24, 24 to 48, 48 to 72 hours after the start of IV infusion, and 0 to 24, 24 to 48, 48 to 72 hours after the end of IV infusion ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||March 2014 (Final data collection date for primary outcome measure)
Experimental: SyB L-1101
Drug: SyB L-1101
SyB L-1101（rigosertib sodium） will be administered to two cohorts at either 1,200 mg/day or 1,800 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.
|Ages Eligible for Study:
||20 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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 WHO classification or FAB classification.
- RA (< 5% myeloblasts, < 15% ringed sideroblasts)
- RARS (< 5% myeloblasts, ≥ 15% ringed sideroblasts)
- RAEB-1 (5% to 9% myeloblasts)
- RAEB-2 (10% to 19% myeloblasts)
- RAEB-t (20% to 29% myeloblasts or < 25,000/mm3 peripheral leukocytes)
- CMML (10% to 19% myeloblasts in marrow, ≥ 1,000/mm3 peripheral monocytes, < 13,000/mm3 leukocytes) However, RA patients must have score of Int-2 or higher in IPSS
Patients with a low value in at least one blood cell lineage (having at least one of the following cytopenias).
- Neutrophils : < 1,800/mm3
- Platelets : < 100,000/mm3
- 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*
- Patients with intolerability that has led to discontinuation of treatment because of the development of liver dysfunction, kidney dysfunction, etc., after the start of treatment. * Proximate therapeutic efficacy judged under IWG2006 criteria
- Patients who have not been treated for four weeks or longer after the end of the previous therapy and who are judged to have no residual effects (antitumor effects) from the previous therapy.
- Patients who can be expected to survive at least three months or longer.
- Patients at least 20 years old (when informed consent is obtained).
- Patients who have score of 0 to 2 in ECOG Performance Status (P.S.).
Patients with adequate function in major organs (heart, lungs, liver, kidneys, etc.).
- AST (GOT): no greater than 3.0 times the upper boundary of the reference range at each institution
- ALT (GPT): no greater than 3.0 times the upper boundary of the reference range at each institution
- Total bilirubin: no more than 1.5 times the upper boundary of the reference range at each institution
- Serum creatinine: no more than 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
- Patients who personally signed an informed consent document for participation in this study.
- 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 G-CSF (granulocyte-colony stimulating factor), 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 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.
Patients will avoid sexual intercourse with sexual partners or should use the following contraceptive methods in these time periods: for male patients during the administration period of the trial and for six months after the end of administration; female patients during the administration period of the trial, and until a second menstrual period is confirmed after the end of administration (or in the case of female patients with no menstrual period, for two months after the end of administration).
The patient will always use a condom. For effective contraception, it is recommended that the female partner also use the contraceptive methods for female patients.
Female patients who may become pregnant should use one or more types of the following contraceptive methods. In addition, the male partner will always use a condom.
- Oral contraceptive (birth control pills)
- Intrauterine device (IUD)
- Tubal ligation
- Other patients judged to be unsuitable by an investigator or sub-investigator.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01700335
|Nagoya, Aichi, Japan |
|Fukuoka, Japan |
|Tokyo, Japan |
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||August 7, 2012
||October 1, 2012
||Japan: Pharmaceuticals and Medical Devices Agency
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 22, 2014
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