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Low-grade B Cell Non-Hodgkin's LymphomaPhase 2NCT01718691

Efficacy and Safety Study of SyB L-0501 in Combination With Rituximab in Patients With Untreated, Low-grade B Cell Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma

A Phase 2 study testing SyB L-0501 and rituximab in people with Low-grade B Cell Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma Where Hematopoietic Stem Cell Transplantation is Not Indicated, run by SymBio Pharmaceuticals at 14 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 assess the efficacy and safety of SyB L-0501 (two-day consecutive 90 mg/m2/day IV drip infusions) in combination with rituximab (375 mg/m2 IV drip infusion) on untreated, low-grade B cell non-Hodgkin's lymphoma and mantle cell lymphoma where hematopoietic stem cell transplantation is… Read more about this study

Who is it for?
Ages 20 to 79 years
What is being tested?
SyB L-0501 and rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
14 sitesJapan
Study dates
Nov 2011to Nov 2013
Phase
Phase 2
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 to 79 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients who are histopathologically confirmed to have the following cluster of differentiation 20 (CD20) positive low-grade B cell non-Hodgkin's lymphoma or mantle cell lymphoma by lymph node biopsy or evaluable tissue biopsy within 6 months before the registration WHO Classification of Tumors (fourth edition):
  • Small lymphocytic lymphoma
  • Splenic marginal zone B-cell lymphoma
  • Lymphoplasmacytic lymphoma
  • Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)
  • Nodal marginal zone B-cell lymphoma
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  • Follicular lymphoma (Grade 1, 2, 3a)
  • Mantle cell lymphoma
  • Patients with a measurable lesion ( > 1.5 cm in major axis on CT)
  • Patients without a medical history
  • Patients with at least 1 of the following clinical symptoms or signs (excluding mantle cell lymphoma):
  • Bulky disease measuring > 7 cm in major axis on CT (excluding spleen)
  • B symptoms
  • Fever exceeding 38.0ºC of unknown cause
  • Night sweats
  • Weight decrease exceeding 10% within 6 months before patient registration
  • Elevated serum LDH or beta 2 microglobulin
  • Three or more regional lymph nodes of > 3 cm in major axis on CT
  • Symptomatic splenomegaly
  • Intracranial pressure
  • Pleural effusion/ascites retention
  • Patients expected to live for at least 3 months
  • Patients aged between 20 and 79 years (at the time of registration)
  • Patients whose Eastern Cooperative Oncology Group (ECOG) performance status (P.S.) is 0~2
  • Patients with adequately maintained major organ function (bone marrow, heart, lungs, liver, kidneys)
  • Neutrophil count: not less than 1,500 /mm3
  • Platelet count: not less than 75,000 /mm3
  • Aspartate aminotransferase (AST)[Glutamic oxaloacetic transaminase (GOT)]: not more than 3 times the standard upper limit for the site
  • Alanine aminotransferase (ALT)[Glutamic pyruvic transaminase (GPT)]: not more than 3 times the standard upper limit for the site
  • Total bilirubin: not more than 1.5 times the standard upper limit for the site
  • Serum creatinine: not more than 1.5 times the standard upper limit for the site
  • Arterial partial pressure of oxygen (PaO2): not less than 65 mmHg
  • Electrocardiogram shows no abnormal findings that require treatment
  • Echocardiogram of left ventricular ejection fraction (LVEF): not less than 55%
  • Patients whose informed consent has been obtained in person

Who cannot join

  • Patients who fall under any one of the following criteria are to be excluded
  • Patients whose transformation has been confirmed histopathologically
  • Mantle cell lymphoma patients aged 65 years or younger
  • Patients who were administered or received transfusion of cytokine formulations such as G-CSF (granulocyte colony stimulating factor) and erythropoietin within 14 days before pre-registration test
  • Patients with severe active infectious disorders (receiving antibiotics, antifungals, or antivirus IV injection)
  • Patients with serious complications (such as hepatic or renal failure)
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  • Patients with severe complications of cardiac disease (examples: myocardial infarction, ischemic heart disease) or its previous history within 2 years before patient registration, and patients with arrhythmia requiring a treatment
  • Patients with serious gastrointestinal conditions (persistent or severe nausea/vomiting or diarrhea)
  • Patients who are positive for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody or HIV antibody [if HBs or hepatitis B core (HBc) positive, patients whose hepatitis B virus (HBV)-DNA test results indicate positive]
  • Patients with serious bleeding tendencies [such as disseminated intravascular coagulation (DIC)]
  • Patients having or suspected of having symptoms indicative of the central nervous system (CNS) involvement
  • Patients with interstitial pneumonitis, pulmonary fibrosis, pulmonary emphysema complications requiring treatment or its medical history.
  • Patients with active multiple primary cancer
  • Patients who received chemotherapy, radiotherapy, antibody therapy and antitumor steroid therapy in the past
  • Patients with complications or medical history of autoimmune haemolytic anaemia
  • Patients who were administered investigative or unapproved drugs within 3 months before patient registration
  • Patients with addiction to drugs or narcotics, or alcoholism
  • Patients who have previously received hematopoietic stem cell transplantation
  • Patients who are or may be pregnant, lactating patients
  • Patients, whether male or female, who do not agree to use contraception
  • Patients otherwise judged by the investigator or the sub-investigator to be unsuitable for inclusion in the study

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

Japan14 sites
  • Research site

    Fukuoka, Fukuoka

  • Research site

    Hamamatsu, Shizuoka

  • Research site

    Isehara, Kanagawa

  • Research site

    Izumo, Shimane

  • Research site

    Kagoshima, Kagoshima-ken

  • Research site

    Kashiwa, Chiba

  • Research site

    Kyoto, Kyoto

  • Research site

    Moriguchi, Osaka

  • Research site

    Nagasaki, Nagasaki

  • Research site

    Nagoya, Aichi-ken

  • Research site

    Sapporo, Hokkaido

  • Research site

    Sendai, Miyagi

  • Research site

    Tokyo, Tokyo

  • Research site

    Utsunomiya, Tochigi

Other trials in Japan

About this study

Official title: Phase II Clinical Study of SyB L-0501 in Combination With Rituximab in Patients With Untreated, Low-grade B-cell Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma (Multicenter, Open-label).

The purpose of this study is to assess the efficacy and safety of SyB L-0501 (two-day consecutive 90 mg/m2/day IV drip infusions) in combination with rituximab (375 mg/m2 IV drip infusion) on untreated, low-grade B cell non-Hodgkin's lymphoma and mantle cell lymphoma where hematopoietic stem cell transplantation is not indicated.

Being tested
SyB L-0501, rituximab

What participants receive

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

  • SyB L-0501Drug

    A dose of 90 mg/m^2/day of SyB L-0501 is administered on Day 1 and Day 2 as an IV drip infusion, followed by 26-day observation. This is 1 cycle (28 days), which will be repeated for a maximum of 6 times.

  • rituximabDrug

    A dose of 375 mg/m^2 of rituximab is administered on Day 1 (Day 0 in Cycle 1 only) as an IV drip infusion, followed by 26-day observation. This is 1 cycle (28 days), which will be repeated for a maximum of 6 times. From Cycle 2, rituximab will be coadministered with SyB L-0501 on Day 1. However, if the investigator or sub-investigator judges that the coadministration is difficult, rituximab may be administered on Day 0.

Study groups in NCT01718691
Study groupRoleWhat they receive
SyB L-0501+rituximabExperimentalNot described
Receives: Drug: SyB L-0501; Drug: rituximab

What is being measured

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

  1. Complete Response Rate (CR + CRu) Based on International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas (1999)(IWRC)

    The criteria for CR and CRu based on IWRC are shown below.

    CR: Fulfills all of the following

    • Disappearance of all detectable disease
    • LN* > 1.5 cm must decrease to ≤ 1.5 cm

    CRu: Fulfills all of the following

    • LN >1.5 cm; SPD** decrease >75%
    • indeterminate bone marrow
    • LN: lymph nodes or nodal masses ** SPD: sum of the products of the greatest diameters

    Measured: Up to 30 weeks

Secondary outcomes (11)
  1. Overall Response Rate (Antitumor Effect: PR or Better) Based on International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas (1999)(IWRC)

    The criteria for PR based on IWRC are shown below.

    PR: SPD regressed > 50%

    Measured: Up to 30 weeks

  2. Complete Response Rate (CR) Based on Revised Response Criteria for Malignant Lymphoma (2007)(Revised RC)

    The criteria for CR based on the Revised RC are shown below.

    Definition: Disappearance of all evidence of disease

    Nodal Masses:

    1. [18F]fluorodeoxyglucose (FDG)-avid or PET positive prior to therapy; mass of any size permitted if PET negative.
    2. Variably FDG-avid or PET negative; regression to normal size on CT.

    Spleen, Liver:

    Not palpable, nodules disappeared

    Bone Marrow:

    Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative.

    Measured: Up to 30 weeks

  3. Overall Response Rate (PR or Better) Based on Revised Response Criteria for Malignant Lymphoma (2007)(Revised RC)

    The criteria for PR based on the Revised RC are shown below.

    Definition: Regression of measurable disease and no new sites

    Nodal Masses:

    50% or more decrease in SPD of up to 6 largest dominant masses; no increase in size of other nodes

    1. FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site
    2. Variably FDG-avid or PET negative; regression on CT

    Spleen, Liver:

    50% or more decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen

    Bone Marrow:

    Irrelevant if positive prior to therapy; cell type should be specified.

    Measured: Up to 30 weeks

  4. Complete Response Rate Based on WHO Handbook for Reporting Results of Cancer Treatment (1979)

    The criteria for Complete response based on WHO Handbook for Reporting Results of Cancer Treatment (1979) are shown below.

    Measurable disease:

    The disappearance of all known disease, determined by 2 observations not less than 4 weeks apart.

    Unmeasurable disease:

    Complete disappearance of all known disease for at least 4 weeks.

    Bone metastases:

    Complete disappearance of all lesions on X-ray or scan for at least 4 weeks.

    Measured: Up to 30 weeks

  5. Overall Response Rate (PR or Better) Based on "WHO Handbook for Reporting Results of Cancer Treatment (1979)"

    The criteria for Overall response rate (PR or better) based on "WHO Handbook for Reporting Results of Cancer Treatment (1979)" are shown below.

    Definition of PR:

    Measurable disease:

    50% or more decrease in total tumor size of the lesions which have been measured to determine the effect of therapy by 2 observations not less than 4 weeks apart. In addition there can be no appearance of new lesions or progression of any lesion.

    Unmeasurable disease:

    Estimated decrease in tumor size of 50% or more for at least 4 weeks.

    Bone metastases:

    Partial decrease in size of lytic lesions, recalcification of lytic lesions, or decreased density of blastic lesions for at least 4 weeks.

    Measured: Up to 30 weeks

  6. Progression-Free Survival (PFS)

    PFS is the period from registration date to the earliest onset date of any progression event calculated using the Kaplan-Meier estimator. The median and the 95% confidence interval (CI) were calculated using Greenwood's formula.

    Progression event was defined as progression (includes recurrence/relapse), initiation of post-study treatment, confirmation of other malignant tumor, or death due to any given cause. The date of progression was determined based on overall response assessed using IWRC, Revised RC, and WHO, and assessment by the primary physicians (excluding overall response).

    Measured: Up to 30 weeks

  7. Duration of Response (DOR)

    DOR is the period from the date of achieving CR, CRu or PR in the responders to the earliest onset date of any progression events calculated using the Kaplan-Meier estimator. The median and the 95% CI were calculated using Greenwood's formula.

    The date of achieving CR, CRu or PR was determined based on the overall response assessed using IWRC. The date of progression was determined based on overall response assessed using IWRC, Revised RC and WHO, and assessment by the primary physicians (excluding overall response).

    Progression event was defined as progression (includes recurrence/relapse), initiation of post-study treatment, confirmation of other malignant tumor, or death due to any given cause.

    Measured: Up to 30 weeks

  8. Overall Survival (OS)

    Death due to any given cause was defined as an event. OS was calculated using the Kaplan-Meier estimator. The median and the 95% CI were calculated using Greenwood's formula.

    Measured: Up to 30 weeks

  9. Number of Subjects With Adverse Event, Related Adverse Event, Serious Adverse Event, and Discontinuation Due to Adverse Event

    Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v4.0, Japan Clinical Oncology Group/Japan Society of Clinical Oncology (JCOG/JSCO) version, and were encoded using Medical Dictionary for Regulatory Activities (MedDRA) Ver.16.1.

    Measured: up to 30 weeks

  10. Laboratory Test Abnormalities (Biochemical Tests)

    Abnormalities in laboratory test values in overall study period were analyzed. Severity of abnormalities were evaluated using CTCAE. Grade 1 : mild Grade 2 : moderate Grade 3 : severe or medically significant but not immediately life-threatening Grade 4 : life threatening or disabling Grade 5 : death related to AE

    Measured: up to 30 weeks

  11. Laboratory Test Abnormalities (Hematology Tests)

    Abnormalities in laboratory test values in overall study period were analyzed. Severity of abnormalities were evaluated using CTCAE. Grade 1 : mild Grade 2 : moderate Grade 3 : severe or medically significant but not immediately life-threatening Grade 4 : life threatening or disabling Grade 5 : death related to AE

    Measured: up to 30 weeks

Timeline

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

  1. First posted31 Oct 2012 (estimated)
  2. Study startNov 2011
  3. Primary completionNov 2013
  4. Study completionNov 2013

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01718691
Sponsor's protocol ID
2011002
Status last verified
Mar 2016
First submitted
29 Oct 2012
Last updated
27 Apr 2016

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing SyB L-0501 and rituximab in people with Low-grade B Cell Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma Where Hematopoietic Stem Cell Transplantation is Not Indicated, run by SymBio Pharmaceuticals at 14 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 35 inclusion and 21 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 27 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 27 Apr 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?

Complete Response Rate (CR + CRu) Based on International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas (1999)(IWRC) (time frame: Up to 30 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 27 Apr 2016.

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