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Myelodysplastic SyndromePhase 1NCT02783547

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

A Phase 1 study testing SyB C-1101 and Azacytidine in people with Myelodysplastic Syndrome, run by SymBio Pharmaceuticals at 4 sites in Japan.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. 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 C-1101 and Azacytidine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
4 sitesJapan
Study dates
Dec 2015to Jun 2017
Phase
Phase 1
Are there results?
None posted in the registry

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 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).
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  • 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.

Who cannot join

  • 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.).
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  • 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.
  • With not properly controlled hypertension (systolic pressure ≧160 mmHg or diastolic pressure ≧110 mmHg).
  • With not properly controlled epileptic seizure or with onset of epileptic seizure within 3 months before the case registration.
  • Has undergone treatment with SyB 1101 in the past.
  • With history of allergic reaction to polyethylene glycol,gelatin capsule or azacytidine.
  • Difficult to participate in the study treatment due to psychiatric disorder, social condition, ect.
  • With drug intoxication, narcotic addiction or alcohol dependency.
  • Is pregnant, nursing or possibly pregnant.
  • Is positive for pregnancy test (female patients) in the examination before the case registration.
  • Not provided consent to the following contraceptive measures. Patients should avoid sexual intercourse with sexual partners or should use the contraceptive methods as described below in the following time periods: for male patients before case registration until 6 months after the end of administration of the study drug; for female patients with menstruation before case registration until the second menstrual period is confirmed after the end of administration; for menopausal women before case registration until 2 months after the end of administration.
  • Male patients Must always use a condom. For effective contraception, it is recommended that contraceptive methods should also be applied by the female sexual partner and patient.
  • Female patients Must use at least 1 of the following contraceptive methods. AT the same time, the male partner must use a condom.
  • Oral contraceptive (birth control pill)
  • Contraceptive injection
  • Contraceptive patch
  • Intrauterine device (IUD)
  • Tubal ligation 24. Disqualified as a subject of study treatment judged by the principal investigator or investigator.

Trial locations and contacts

4 sites in 1 country.

Japan4 sites

  • Research Site

    Kakamigahara, Gifu

  • Research Site

    Nagoya, Aichi-ken

  • Research Site

    Sendai, Miyagi

  • Research Site

    Shinagawa, Tokyo

Other trials in Japan

About this study

Official title: A Phase 1, Open Label, Multicentre Clinical Trial of SyB C-1101 in Combination With Azacytidine in Patients With Myelodysplastic Syndrome

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.

Being tested
SyB C-1101 and Azacytidine
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 C-1101 and AzacytidineDrug

    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.

Study groups in NCT02783547
Study groupRoleWhat they receive
SyB C-1101 and AzacytidineExperimentalNot described
Receives: Drug: SyB C-1101 and Azacytidine

What is being measured

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

  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

    Measured: Up to 19 months

Secondary outcomes (10)

  1. Serious Adverse Events

    Measured: Up to 19 months

  2. Adverse Events, not including Serious Adverse Events

    Measured: Up to 19 months

  3. Change in laboratory values

    Measured: Up to 19 months

  4. Total efficacy in hematologic remission rate

    Ratio of patients scored as complete remission (CR), partial remission (PR) or marrow CR) according to the International Working Group (IWG) response criteria in myelodysplasia, 2006 (in each response criteria, responses must last at least 4 weeks):

    < CR>

    • Bone marrow: ≤5% myeloblasts with normal maturation of all cell lines.
    • Persistent dysplasia will be noted.
    • Peripheral blood:

    Hgb ≥ 11 g/dL Platelets ≥ 100 × 109/L Neutrophils ≥ 1.0 × 109/L† Blasts 0% < PR >

    All CR criteria if abnormal before treatment except:

    • Bone marrow blasts decreased by ≥ 50% over pretreatment but still > 5%
    • Cellularity and morphology not relevant <marrow CR>
    • Bone marrow: ≤ 5% myeloblasts and decrease by ≥ 50% over pretreatment
    • Peripheral blood: if hematological improvement (HI) responses, they will be noted in addition to marrow CR.

    Measured: Up to 19 months

  5. Total efficacy in hematologic improvement rate

    Ratio of patients with hematologic improvement(erythroid, platelet or neutrophil) according to the International Working Group (IWG) response criteria in myelodysplasia, 2006 (in each response criteria, responses must last at least 8 weeks):

    < Erythroid response (pretreatment, <11 g/dL) >

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

    < Platelet response (pretreatment, <100 × 109/L) >

    1. Absolute increase of ≥30 × 109/L for patients starting with >20 × 109/L platelets
    2. Increase from <20 × 109/L to >20 × 109/L and by at least 100%

    < Neutrophil response (pretreatment, <1.0 × 109/L) > At least 100% increase and an absolute increase >0.5 × 109/L

    Measured: Up to 19 months

  6. Cytogenetic response rate

    Ratio of patients scored as complete cytogenetic response or partial cytogenetic response) according to the International Working Group (IWG) response criteria in myelodysplasia, 2006 (in each response criteria, responses must last at least 4 weeks):

    < Cytogenetic response > Complete: Disappearance of the chromosomal abnormality without appearance of new ones.

    Partial: At least 50% reduction of the chromosomal abnormality.

    Measured: Up to 19 months

  7. Peak plasma concentration (Cmax)

    Measured: Up to 19 months

  8. Time to maximum drug concentration time (tmax)

    Measured: Up to 19 months

  9. Area under the plasma concentration-time curve (AUC)

    Measured: Up to 19 months

  10. Elimination half-life (t1/2)

    Measured: Up to 19 months

Timeline

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

  1. First posted26 May 2016 (estimated)
  2. Study startDec 2015
  3. Primary completionJun 2017 (estimated)
  4. Study completionJun 2017 (estimated)

Why it stopped: The trial was withdrawn due to problems with the manufacture of the investigational drug.

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02783547
Sponsor's protocol ID
2015001
Status last verified
Nov 2022
First submitted
6 Mar 2016
Last updated
17 Nov 2022
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SyB C-1101 and Azacytidine in people with Myelodysplastic Syndrome, run by SymBio Pharmaceuticals at 4 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 15 inclusion and 31 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: withdrawn, as of the sponsor's last update on 17 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 4 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?

The study was withdrawn before enrolling participants, so there are no results.

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 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 (time frame: Up to 19 months). 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 NCT02783547.

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 17 Nov 2022.

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