Back to resultsStudy of SyB L-0501 in Combination With Rituximab to Treat Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Primary Purpose
Non-Hodgkin's Lymphoma, Lymphoma, Large Cell, Diffuse, Mantle Cell Lymphoma, Lymphoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SyB L-0501
Rituximab
Sponsored by
About this trial
This is an interventional treatment trial for Non-Hodgkin's Lymphoma focused on measuring Non-Hodgkin's lymphoma, Lymphoma, Large B-Cell, Diffuse, Mantle cell lymphoma, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse
Eligibility Criteria
Inclusion Criteria:
- Patients with documented Cluster of differentiation 20 (CD20)-positive for lymphoma cells
- Patients with measurable lesions
- Patients with measurable lesions >1.5 cm in major axes
- Relapsed or refractory after 1 to 3 prior therapeutic treatments for diffuse large B-cell lymphoma.
- Patients who are expected to survive for at least 3 months
- Patients aged from 20 to 75 years at the time informed consent is obtained
- Performance Status (P.S.) of 0 to 1 at initial administration of the study drug
- Patients with adequately maintained organ functions
- Patients capable of personally giving voluntary informed consent in writing to participate in the study
Exclusion Criteria:
- Patients who have been without treatment for less than 3 weeks after prior treatment
- Patients who can be candidates for autologous peripheral blood stem cell transplantation at the discretion of the investigator.
- Patients who received adequate prior treatments and did not respond to any of them.
- Patients with central nervous system (CNS) involvement or patients with clinical symptoms suggestive of CNS involvement.
- Patients with serious, active infections
- Patients with serious complications
- Patients with complications or medical history of serious cardiac disease
- Patients with serious gastrointestinal symptoms
- Patients with malignant pleural effusion, cardiac effusion, or ascites retention
- Patients positive for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, or HIV antibody
- Patients with serious bleeding tendencies
- Patients with a fever of 38.0°C or higher
- Patients with, or confirmed in the past to have had, interstitial pneumonia, pulmonary fibrosis, or pulmonary emphysema
- Patients with active multiple primary cancer or patients with a history of other malignant cancer within the past 5 years, except for basal cell cancer of the skin, squamous cell cancer, or cervical cancer in situ
- Patients with, or confirmed in the past to have had, autoimmune hemolytic anemia
- Patients who received SyB L-0501 in the past
- Patients who received cytokine preparation such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) or blood transfusions within 2 weeks before the examination at registration for this study
- Patients who received other investigational products or unapproved medication within 3 months before registration in this study
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SyB L-0501
Arm Description
Outcomes
Primary Outcome Measures
The Overall Response Rate [Complete Response (CR) + Partial Response (PR)] Determined on the Basis of Revised Response Criteria for Malignant Lymphoma
CR: Disappearance of all evidence of disease. PR: Regression of measurable disease and no new sites.
For the criteria for CR, See Outcome measure 2 description.
The criteria for PR is as below.
Nodal Masses:
more than 50% decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes
FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site
Variably FDG-avid or PET negative; regression on CT
Spleen, Liver:
more than 50% 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
Secondary Outcome Measures
The Complete Response (CR) Rate Determined on the Basis of Revised Response Criteria for Malignant Lymphoma
The criteria for CR is as below
Nodal Masses:
fluorodeoxy glucose (FDG)-avid or positron emission tomography (PET) positive prior to therapy; mass of any size permitted if PET negative
Variably FDG-avid or PET negative; regression to normal size on computed tomography (CT)
Spleen, Liver:
Not palpable, nodules disappeared
Bone Marrow:
Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative
Progression Free Survival (PFS)
PFS = day of the first PFS event - day of start of study treatment + 1
The definitions of PFS event are as below.
PD according to overall response on the basis of Revised Response Criteria for Malignant Lymphoma
PD: Any new lesion or increase by ≥50% of previously involved sites from nadir. Nodal masses; Appearance of a new lesion(s) >1.5 cm in any axis, ≥50% increase in SPD of more than one node, or ≥50% increase in longest diameter of a previously identified node >1 cm in short axis. Lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. Spleen, Liver; ≥50% increase from nadir in the SPD of any previous lesions. Bone marrow; New or recurrent involvement
Disease progression during treatment period
Disease progression during follow up period
Start of treatment of new lesion
Occurrence of other multiple malignant tumors
Death
Number of Subjects With Adverse Event
Number of Adverse Events
Number of Subjects With Abnormality (Grade ≥3) in Laboratory Test Values
Abnormalities in laboratory test values in overall study period were analyzed. Severity of abnormalities were evaluated using Common Terminology Criteria for Adverse Events (CTCAE).
grade 1 : mild grade 2 : moderate grade 3 : severe grade 4 : life threatening or disabling grade 5 : death related to adverse event
Number of Subjects With Grade ≥3 Physical Examination Finding
Concomitant Medication Usage
The Maximum Concentration (Cmax) of Unchanged SyB L-0501 in Japan
The Maximum Drug Concentration Time (Tmax) of Unchanged SyB L-0501 in Japan
The Area Under the Curve (AUC) for Unchanged SyB L-0501 in Japan
The Half-life Period (t1/2) of Unchanged SyB L-0501 in Japan
The Maximum Concentration (Cmax) of Unchanged SyB L-0501 in Korea
The Maximum Drug Concentration Time (Tmax) of Unchanged SyB L-0501 in Korea
The Area Under the Curve (AUC) for Unchanged SyB L-0501 in Korea
The Half-life Period (t1/2) of Unchanged SyB L-0501 in Korea
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01118845
Brief Title
Study of SyB L-0501 in Combination With Rituximab to Treat Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Official Title
A Multinational, Multicenter, Open-Label Phase II Study of SyB L-0501 in Combination With Rituximab in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
April 2010 (undefined)
Primary Completion Date
October 2011 (Actual)
Study Completion Date
October 2011 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
SymBio Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine the efficacy of SyB L-0501 in combination with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma.
Detailed Description
Primary Objective is to determine the efficacy, as measured by overall response rate on the basis of Revised Response Criteria for Malignant Lymphoma, of SyB L-0501 at 120 mg/m^2/day on day2 and 3 in combination with rituximab at 375 mg/m^2 on day 1 of each 21-day cycle in patients with relapsed/refractory diffuse large B-cell lymphoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin's Lymphoma, Lymphoma, Large Cell, Diffuse, Mantle Cell Lymphoma, Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse
Keywords
Non-Hodgkin's lymphoma, Lymphoma, Large B-Cell, Diffuse, Mantle cell lymphoma, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
63 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SyB L-0501
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
SyB L-0501
Other Intervention Name(s)
Bendamustine hydrochloride
Intervention Description
The administration of SyB L-0501 at 120 mg/m^2/day by intravenous infusion on day 2 and 3 of each 21-day cycle with up to 6 cycles. Dose modifications are permitted from 2nd cycle according to dose reduction schedule.
SyB L-0501 60 mg/m^2, 90 mg/m^2 or 120 mg/m^2/day on Day 2 and Day 3 will be followed by 18 days of observation.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
The administration of rituximab at 375 mg/m^2/day by intravenous infusion on day 1 of each 21-day cycle with up to 6 cycles. Dose modifications are not permitted.
Primary Outcome Measure Information:
Title
The Overall Response Rate [Complete Response (CR) + Partial Response (PR)] Determined on the Basis of Revised Response Criteria for Malignant Lymphoma
Description
CR: Disappearance of all evidence of disease. PR: Regression of measurable disease and no new sites.
For the criteria for CR, See Outcome measure 2 description.
The criteria for PR is as below.
Nodal Masses:
more than 50% decrease in sum of the product of the perpendicular diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes
FDG-avid or PET positive prior to therapy; one or more PET positive at previously involved site
Variably FDG-avid or PET negative; regression on CT
Spleen, Liver:
more than 50% 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
Time Frame
up to 30 weeks
Secondary Outcome Measure Information:
Title
The Complete Response (CR) Rate Determined on the Basis of Revised Response Criteria for Malignant Lymphoma
Description
The criteria for CR is as below
Nodal Masses:
fluorodeoxy glucose (FDG)-avid or positron emission tomography (PET) positive prior to therapy; mass of any size permitted if PET negative
Variably FDG-avid or PET negative; regression to normal size on computed tomography (CT)
Spleen, Liver:
Not palpable, nodules disappeared
Bone Marrow:
Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative
Time Frame
up to 30 weeks
Title
Progression Free Survival (PFS)
Description
PFS = day of the first PFS event - day of start of study treatment + 1
The definitions of PFS event are as below.
PD according to overall response on the basis of Revised Response Criteria for Malignant Lymphoma
PD: Any new lesion or increase by ≥50% of previously involved sites from nadir. Nodal masses; Appearance of a new lesion(s) >1.5 cm in any axis, ≥50% increase in SPD of more than one node, or ≥50% increase in longest diameter of a previously identified node >1 cm in short axis. Lesions PET positive if FDG-avid lymphoma or PET positive prior to therapy. Spleen, Liver; ≥50% increase from nadir in the SPD of any previous lesions. Bone marrow; New or recurrent involvement
Disease progression during treatment period
Disease progression during follow up period
Start of treatment of new lesion
Occurrence of other multiple malignant tumors
Death
Time Frame
up to 30 weeks
Title
Number of Subjects With Adverse Event
Time Frame
up to 30 weeks
Title
Number of Adverse Events
Time Frame
up to 30 weeks
Title
Number of Subjects With Abnormality (Grade ≥3) in Laboratory Test Values
Description
Abnormalities in laboratory test values in overall study period were analyzed. Severity of abnormalities were evaluated using Common Terminology Criteria for Adverse Events (CTCAE).
grade 1 : mild grade 2 : moderate grade 3 : severe grade 4 : life threatening or disabling grade 5 : death related to adverse event
Time Frame
up to 30 weeks
Title
Number of Subjects With Grade ≥3 Physical Examination Finding
Time Frame
up to 30 weeks
Title
Concomitant Medication Usage
Time Frame
up to 30 weeks
Title
The Maximum Concentration (Cmax) of Unchanged SyB L-0501 in Japan
Time Frame
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Title
The Maximum Drug Concentration Time (Tmax) of Unchanged SyB L-0501 in Japan
Time Frame
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Title
The Area Under the Curve (AUC) for Unchanged SyB L-0501 in Japan
Time Frame
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Title
The Half-life Period (t1/2) of Unchanged SyB L-0501 in Japan
Time Frame
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Title
The Maximum Concentration (Cmax) of Unchanged SyB L-0501 in Korea
Time Frame
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Title
The Maximum Drug Concentration Time (Tmax) of Unchanged SyB L-0501 in Korea
Time Frame
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Title
The Area Under the Curve (AUC) for Unchanged SyB L-0501 in Korea
Time Frame
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
Title
The Half-life Period (t1/2) of Unchanged SyB L-0501 in Korea
Time Frame
Prior to and 30 min after start of administration, and 0, 30, 60, 120 min after completion of administration on Day 2 of the 1st cycle
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with documented Cluster of differentiation 20 (CD20)-positive for lymphoma cells
Patients with measurable lesions
Patients with measurable lesions >1.5 cm in major axes
Relapsed or refractory after 1 to 3 prior therapeutic treatments for diffuse large B-cell lymphoma.
Patients who are expected to survive for at least 3 months
Patients aged from 20 to 75 years at the time informed consent is obtained
Performance Status (P.S.) of 0 to 1 at initial administration of the study drug
Patients with adequately maintained organ functions
Patients capable of personally giving voluntary informed consent in writing to participate in the study
Exclusion Criteria:
Patients who have been without treatment for less than 3 weeks after prior treatment
Patients who can be candidates for autologous peripheral blood stem cell transplantation at the discretion of the investigator.
Patients who received adequate prior treatments and did not respond to any of them.
Patients with central nervous system (CNS) involvement or patients with clinical symptoms suggestive of CNS involvement.
Patients with serious, active infections
Patients with serious complications
Patients with complications or medical history of serious cardiac disease
Patients with serious gastrointestinal symptoms
Patients with malignant pleural effusion, cardiac effusion, or ascites retention
Patients positive for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, or HIV antibody
Patients with serious bleeding tendencies
Patients with a fever of 38.0°C or higher
Patients with, or confirmed in the past to have had, interstitial pneumonia, pulmonary fibrosis, or pulmonary emphysema
Patients with active multiple primary cancer or patients with a history of other malignant cancer within the past 5 years, except for basal cell cancer of the skin, squamous cell cancer, or cervical cancer in situ
Patients with, or confirmed in the past to have had, autoimmune hemolytic anemia
Patients who received SyB L-0501 in the past
Patients who received cytokine preparation such as erythropoietin or granulocyte colony-stimulating factor (G-CSF) or blood transfusions within 2 weeks before the examination at registration for this study
Patients who received other investigational products or unapproved medication within 3 months before registration in this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kensei Tobinai, MD, Ph D
Organizational Affiliation
National Cancer Center Hospital
Official's Role
Study Chair
Facility Information:
City
Nagoya
State/Province
Aichi
Country
Japan
City
Matsuyama
State/Province
Ehime
Country
Japan
City
Kurume
State/Province
Fukuoka
Country
Japan
City
Maebashi
State/Province
Gunma
Country
Japan
City
Sapporo
State/Province
Hokkaido
Country
Japan
City
Kanazawa
State/Province
Ishikawa
Country
Japan
City
Isehara
State/Province
Kanagawa
Country
Japan
City
Ninomaru
State/Province
Kumamoto
Country
Japan
City
Sendai
State/Province
Miyagi
Country
Japan
City
Kita-ku
State/Province
Okayama
Country
Japan
City
Kurashiki
State/Province
Okayama
Country
Japan
City
Hidaka
State/Province
Saitama
Country
Japan
City
Izumo
State/Province
Shimane
Country
Japan
City
Chuo-ku
State/Province
Tokyo
Country
Japan
City
Akita
Country
Japan
City
Fukuoka
Country
Japan
City
Kagoshima
Country
Japan
City
Kyoto
Country
Japan
City
Seo-gu
State/Province
Busan
Country
Korea, Republic of
City
Jung-gu
State/Province
Daegu
Country
Korea, Republic of
City
Goyang-si
State/Province
Gyeonggi-do
Country
Korea, Republic of
City
Hwasun-gun
State/Province
Jeonnam
Country
Korea, Republic of
City
Gangnam-gu
State/Province
Seoul
Country
Korea, Republic of
City
Seodaemun-gu
State/Province
Seoul
Country
Korea, Republic of
City
Songpa-gu
State/Province
Seoul
Country
Korea, Republic of
12. IPD Sharing Statement
Learn more about this trial
Study of SyB L-0501 in Combination With Rituximab to Treat Relapsed/Refractory Diffuse Large B-Cell Lymphoma
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