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Myelodysplastic SyndromePhase 1NCT01700335

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

A Phase 1 study testing SyB L-1101 in people with Myelodysplastic Syndrome, run by SymBio Pharmaceuticals at 3 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Myelodysplastic Syndrome
What is being tested?
SyB L-1101
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
3 sitesJapan
Study dates
Jun 2012to Feb 2015
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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*
  • 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 International Working Group (IWG) 2006 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 Eastern Cooperative Oncology Group (ECOG) Performance Status (P.S.).
  • Patients with adequate function in major organs (heart, lungs, liver, kidneys, etc.).
  • Aspartate aminotransferase (AST) (Glutamic oxaloacetic transaminase, GOT) : no greater than 3.0 times the upper boundary of the reference range at each institution
  • Alanine aminotransferase (ALT) (Glutamic pyruvic transaminase, 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.

Who cannot join

  • 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.).
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  • 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.
  • 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).
  • •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.
  • •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.

Trial locations and contacts

3 sites in 1 country.

Japan3 sites

  • Research Site

    Fukuoka

  • Research Site

    Nagoya, Aichi-ken

  • Research Site

    Tokyo

Other trials in Japan

About this study

Official title: Phase I Clinical Trial of SyB L-1101 in Patients With Myelodysplastic Syndrome

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.

Being tested
SyB L-1101
Medical subject headings
Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SyB L-1101Drug

    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.

Study groups in NCT01700335
Study groupRoleWhat they receive
SyB L-1101ExperimentalIn 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.
Receives: Drug: SyB L-1101

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to 60 weeks

Secondary outcomes (2)

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

    Definition

    Complete remission (CR) Bone marrow: <= 5% myeloblasts; normal maturation of all cell lines Peripheral blood: Hemoglobin (Hgb) >= 11 g/dL, Platelets >= 100×10^9/L, Neutrophils >= 1.0×10^9/L, Blasts 0%

    Partial remission (PR) Same as CR criteria except bone marrow blasts decreased by >= 50% over pretreatment but still > 5%

    Marrow CR Bone marrow: <= 5% myeloblasts and decrease by >= 50% over pretreatment Peripheral blood: will be noted in addition to marrow CR

    Stable disease Failure to achieve at least PR, but no evidence of progression for > 8 wks

    Disease progression

    Patients with:

    Less than 5% blasts: >= 50% increase in blasts to > 5% blasts 5%-10% blasts: >= 50% increase to > 10% blasts 10%-20% blasts: >= 50% increase to > 20% blasts 20%-30% blasts: >= 50% increase to > 30% blasts

    Any of the following:

    At least 50% decrement from maximum remission/response in granulocytes or platelets Reduction in Hgb by >= 2 g/dL Transfusion dependence

    Measured: Up to 60 weeks

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

    Definition

    Hematologic Improvement Erythrocyte (HI-E):

    Hgb increase by >= 1.5 g/dL Relevant reduction of units of red blood cell (RBC) transfusions by an absolute number of at least 4 RBC transfusions/8 week compared with the pretreatment transfusion number in the previous 8 week. Only RBC transfusions given for a Hgb of <= 9.0 g/dL pretreatment will count in the RBC transfusion response evaluation

    Hematologic Improvement Platelet (HI-P):

    Absolute increase of >= 30×10^9/L for patients starting with > 20×10^9/L platelets Increase from < 20×10^9/L to > 20×10^9/L and by at least 100%

    Hematologic Improvement Neutrophil (HI-N):

    At least 100% increase and an absolute increase > 0.5×10^9/L

    Progressive disease / Relapse:

    At least 1 of the following:

    At least 50% decrement from maximum response levels in granulocytes or platelets Reduction in Hgb by >= 1.5 g/dL Transfusion dependence

    Measured: Up to 60 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Oct 2012 (estimated)
  2. Study startJun 2012
  3. Primary completionFeb 2015
  4. Study completionFeb 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01700335
Sponsor's protocol ID
2011005
Status last verified
Oct 2022
First submitted
7 Aug 2012
Last updated
21 Nov 2022

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SyB L-1101 in people with Myelodysplastic Syndrome, run by SymBio Pharmaceuticals at 3 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) (time frame: Up to 60 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01700335.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2022.

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