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

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

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.

Study Overview

• Status: Completed
• Conditions: Follicular Lymphoma; Non-Hodgkin's Lymphoma; Lymphoma, Large Cell; Diffuse, Mantle Cell Lymphoma, Lymphoma; Large B-Cell, Diffuse
• Intervention / Treatment: Drug: SyB L-0501; Drug: Rituximab

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.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Akita, Japan
  • Fukuoka, Japan
  • Kagoshima, Japan
  • Kyoto, Japan
  • Aichi
    • Nagoya, Aichi, Japan
  • Ehime
    • Matsuyama, Ehime, Japan
  • Fukuoka
    • Kurume, Fukuoka, Japan
  • Gunma
    • Maebashi, Gunma, Japan
  • Hokkaido
    • Sapporo, Hokkaido, Japan
  • Ishikawa
    • Kanazawa, Ishikawa, Japan
  • Kanagawa
    • Isehara, Kanagawa, Japan
  • Kumamoto
    • Ninomaru, Kumamoto, Japan
  • Miyagi
    • Sendai, Miyagi, Japan
  • Okayama
    • Kita-ku, Okayama, Japan
    • Kurashiki, Okayama, Japan
  • Saitama
    • Hidaka, Saitama, Japan
  • Shimane
    • Izumo, Shimane, Japan
  • Tokyo
    • Chuo-ku, Tokyo, Japan
• Korea, Republic of
  • Busan
    • Seo-gu, Busan, Korea, Republic of
  • Daegu
    • Jung-gu, Daegu, Korea, Republic of
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of
  • Jeonnam
    • Hwasun-gun, Jeonnam, Korea, Republic of
  • Seoul
    • Gangnam-gu, Seoul, Korea, Republic of
    • Seodaemun-gu, Seoul, Korea, Republic of
    • Songpa-gu, Seoul, Korea, Republic of

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SyB L-0501

Drug: SyB L-0501; 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.; Other Names: Bendamustine hydrochloride; Drug: Rituximab; 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.

What is the study measuring?

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 LymphomaPD: 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

Collaborators and Investigators

• Sponsor: SymBio Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: May 1, 2010
• First Submitted That Met QC Criteria: May 6, 2010
• First Posted (Estimate): May 7, 2010

Study Record Updates

• Last Update Posted (Estimate): July 4, 2013
• Last Update Submitted That Met QC Criteria: May 29, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Non-Hodgkin's lymphoma; Lymphoma, Large B-Cell; Diffuse, Mantle cell lymphoma, Lymphoma; Follicular, Lymphoma; Large B-Cell, Diffuse
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, B-Cell; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Immunological; Bendamustine Hydrochloride; Rituximab
• Other Study ID Numbers: 2010001