Study of SyB L-0501 in Combination With Rituximab to Treat Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Non-Hodgkin's Lymphoma, Lymphoma, Large Cell, Diffuse, Mantle Cell Lymphoma, Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse

Intervention / Treatment
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* Drug: SyB L-0501
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SyB L-0501<br> | Drug: SyB L-0501<br>* 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.<br>* Other names: Bendamustine hydrochloride;Drug: Rituximab<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | up to 30 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | up to 30 weeks | 
| 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 | up to 30 weeks | 
| Number of Subjects With Adverse Event |  | up to 30 weeks | 
| Number of Adverse Events |  | up to 30 weeks | 
| 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 | up to 30 weeks | 
| Number of Subjects With Grade ≥3 Physical Examination Finding |  | up to 30 weeks | 
| Concomitant Medication Usage |  | up to 30 weeks | 
| The Maximum Concentration (Cmax) of Unchanged SyB L-0501 in Japan |  | 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 | 
| The Maximum Drug Concentration Time (Tmax) of Unchanged SyB L-0501 in Japan |  | 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 | 
| The Area Under the Curve (AUC) for Unchanged SyB L-0501 in Japan |  | 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 | 
| The Half-life Period (t1/2) of Unchanged SyB L-0501 in Japan |  | 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 | 
| The Maximum Concentration (Cmax) of Unchanged SyB L-0501 in Korea |  | 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 | 
| The Maximum Drug Concentration Time (Tmax) of Unchanged SyB L-0501 in Korea |  | 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 | 
| The Area Under the Curve (AUC) for Unchanged SyB L-0501 in Korea |  | 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 | 
| The Half-life Period (t1/2) of Unchanged SyB L-0501 in Korea |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Hodgkin's lymphoma, Lymphoma, Large B-Cell, Diffuse, Mantle cell lymphoma, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse