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

Myelodysplastic Syndrome Clinical Trial

Official title:

Phase I Clinical Trial of SyB L-1101 in Patients With Myelodysplastic Syndrome - Extension Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02000154
• Other study ID #: 2012001
• Status: Recruiting
• Phase: Phase 1
• First received: November 26, 2013
• Last updated: December 2, 2013
• Start date: October 2012
• Est. completion date: September 2015

Study information

• Verified date: November 2013
• Source: SymBio Pharmaceuticals
• Contact: Yuki Endo
• Phone: +81-3-5472-1127
• Email: yendo.rsvp[@]symbiopharma.com
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

This is an extension study study to investigate long term safety of SyB L-1101 when administered intravenously every 4 weeks to the patients who have completed 8 cycles in the study 2011005 whose purpose is to investigate tolerability of SyB L-1101 when administered intravenously in patients with recurrent/relapsed or refractory myelodysplastic syndrome. Antitumor effects will also be investigated in this study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: September 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

Patients must satisfy the following conditions listed below.

1. Patients enrolled in the study 2011005 of SyB L-1101 in Patients With Myelodysplastic Syndrome.

2. Patients who was not judged as disease progression* nor progressive disease/relapsed** at the end of the cycle 8 in the study 2011005. * hematologic remission according to IWG 2006 criteria ** hematologic improvement according to IWG 2006 criteria

3. Patients who met the continuation criteria*** after Cycle 8 week 2 (Day 15±3) in the study 2011005.***defined in the study 2011005 protocol

4. Patients who can be expected to survive at least three months or longer.

5. Patients who have score of 0 to 2 in Eastern Cooperative Oncology Grou (ECOG) Performance Status (P.S.).

6. Patients with adequate function in major organs (heart, lungs, liver, kidneys, etc.).

• Aspartate aminotransferase (AST): no more than 3.0 times the upper boundary of the reference range at each institution

• Alanine aminotransferase (ALT): no more 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

7. Patients who personally signed an informed consent document for participation in this study.

Exclusion Criteria:

Patients who satisfy any of the following conditions will not be enrolled in the study.

1. Patients with anemia (haemolytic anaemia, gastrointestinal haemorrhage, etc.) caused by factors other than MDS.

2. Patients with obvious infectious diseases (including viral infections).

3. Patients with serious complications (liver failure, renal failure, etc.).

4. Patients with a complication of serious heart disease (myocardial infarction, ischemic heart disease, etc.)

5. Patients with a serious gastrointestinal condition (severe or significant nausea/vomiting, diarrhea, etc.)

6. Patients with serious bleeding tendencies (disseminated intravascular coagulation (DIC), internal hemorrhage, etc.).

7. Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <130 milliequivalent/L).

8. Patients with an addiction to a legal or illegal drug, or with alcohol dependency.

9. Patients who are nursing, pregnant or may become pregnant.

10. 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). (1) Male patients: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. (2) 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

11. Other patients judged to be unsuitable by an investigator or sub-investigator.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• SyB L-1101
SyB L-1101 (rigosertib sodium) will be administered intravenously 72 continuous hours (3 days), followed by 25-day observation period. The treatment period of 28 days (3 days of administration + 25 days of observation) constitutes 1 cycle. The dose at cycle 8 in the study 2011005 will be the dose (if needed, the dose can be reduced) at the first cycle in this study (cycle 9). From cycle 10 on, the dose of SyB L-1101 will be reduced, delayed, or discontinued according to adverse events and results of observation at the previous cycle.

Locations

Country	Name	City	State
Japan	Research Site	Fukuoka
Japan	Research site	Isesaki	Kanagawa
Japan	Research Site	Kagoshima
Japan	Research Site	Kawagoe	Saitama
Japan	Research Site	Kumamoto
Japan	Research Site	Kurashiki	Okayama
Japan	Research Site	Nagoya	Aichi
Japan	Research Site	Sendai	Miyagi
Japan	Research Site	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
SymBio Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Adverse events (type, frequency, severity, reversibility)	Up to 3 years	Yes
Secondary	Total efficacy in hematologic remission ratio according to clinical application and proposal for modification of the International Working Group response criteria in myelodysplasia (IWG) 2006 criteria	Total efficacy in hematologic remission ratio [ratio of patients scored as complete remission (CR), partial remission (PR), or marrow CR according to IWG 2006 criteria]. Definitions of CR, PR, marrow CR are shown below.; CR: Bone marrow: =5% myeloblasts with normal maturation of 3 cell lines (persistent dysplasia should be noted) Peripheral blood: All of the following conditions are met when blood transfusion therapy and cytokine therapy are ineffective. *Hb =11g/dL *platelets=100,000/µL *Neutrophils =1000/µL *blasts 0%; PR: All CR criteria met, except following Bone marrow: Blasts decreased by =50% compared to base-line but still >5%(peripheral blood findings must be normal same as CR) marrow CR: Bone marrow:=5% blasts and decreased by =50%, but peripheral blood findings do not meet criteria for CR (Hematological improvement: Hematologic improvement responses should be noted, such as: Marrow CR with Hematologic improvement-erythroid, marrow CR without Hematologic improvement)	Up to 3 years	No
Secondary	Total efficacy in hematologic improvement ratio according to IWG 2006 criteria Total efficacy in hematologic improvement ratio according to IWG 2006 criteria	Total efficacy in hematologic improvement ratio (ratio of patients scored as hematologically improved "erythrocyte lineage, platelet lineage, or neutrophil lineage") according to IWG 2006 criteria. Definition of hematologic improvement is shown below.; Hematologic improvement-erythroid(base-line <11 g/dL): =1.5 g/dL increase in Hb; Decrease of =4 units/8 weeks in blood transfusion volume compared to base-line (only cases of blood transfusion given for Hb =9 g/dL will be assessed based on transfusion volume); Hematologic improvement-platelet (base-line <100,000/µL): Cases with =20,000/µL: =30,000/µL increase compared to base-line; Cases with <20,000/µL: Increase to =20,000/µL, with at least a 2-fold increase in base-line level; Hematologic improvement-neutrophil(base-line <1,000/µL): At least a 2-fold increase in base-line level, to =500/µL	Up to 3 years	No
Secondary	Cytogenetic response ratio according to IWG 2006 criteria	Cytogenetic response ratio (ratio of patients scored as complete cytogenetic response or partial cytogenetic response) according to IWG 2006 criteria. Definitions of complete cytogenetic response and partial cytogenetic response are shown below.; Complete cytogenetic response: Disappearance of chromosomal abnormality, without appearance of any new karyotype abnormalities; Partial cytogenetic response: =50% reduction compared to base-line	Up to 3 years	No
Secondary	Overall Survival	Overall Survival is the period from the date of patient registration to the date of death.	Up to 3 years	No
Secondary	Changes in clinical laboratory test results	Clinical laboratory test results throughout the study.	Up to 3 years	Yes