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

This study has been completed.
Sponsor:
Information provided by:
SymBio Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01118845
First received: May 1, 2010
Last updated: May 29, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Non-Hodgkin's Lymphoma
Lymphoma, Large Cell
Diffuse, Mantle Cell Lymphoma, Lymphoma
Follicular Lymphoma
Large B-Cell, Diffuse
Drug: SyB L-0501
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by SymBio Pharmaceuticals:

Primary Outcome Measures:
  • The Overall Response Rate [Complete Response (CR) + Partial Response (PR)] Determined on the Basis of Revised Response Criteria for Malignant Lymphoma [ Time Frame: up to 30 weeks ] [ Designated as safety issue: No ]

    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

    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:

    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 [ Time Frame: up to 30 weeks ] [ Designated as safety issue: No ]

    The criteria for CR is as below

    Nodal Masses:

    1. fluorodeoxy glucose (FDG)-avid or positron emission tomography (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 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) [ Time Frame: up to 30 weeks ] [ Designated as safety issue: No ]

    PFS = day of the first PFS event - day of start of study treatment + 1

    The definitions of PFS event are as below.

    1. 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

    2. Disease progression during treatment period
    3. Disease progression during follow up period
    4. Start of treatment of new lesion
    5. Occurrence of other multiple malignant tumors
    6. Death

  • Number of Subjects With Adverse Event [ Time Frame: up to 30 weeks ] [ Designated as safety issue: Yes ]
  • Number of Adverse Events [ Time Frame: up to 30 weeks ] [ Designated as safety issue: Yes ]
  • Number of Subjects With Abnormality (Grade ≥3) in Laboratory Test Values [ Time Frame: up to 30 weeks ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: up to 30 weeks ] [ Designated as safety issue: Yes ]
  • Concomitant Medication Usage [ Time Frame: up to 30 weeks ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: April 2010
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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.

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.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01118845

Locations
Japan
Nagoya, Aichi, Japan
Matsuyama, Ehime, Japan
Kurume, Fukuoka, Japan
Maebashi, Gunma, Japan
Sapporo, Hokkaido, Japan
Kanazawa, Ishikawa, Japan
Isehara, Kanagawa, Japan
Ninomaru, Kumamoto, Japan
Sendai, Miyagi, Japan
Kita-ku, Okayama, Japan
Kurashiki, Okayama, Japan
Hidaka, Saitama, Japan
Izumo, Shimane, Japan
Chuo-ku, Tokyo, Japan
Akita, Japan
Fukuoka, Japan
Kagoshima, Japan
Kyoto, Japan
Korea, Republic of
Seo-gu, Busan, Korea, Republic of
Jung-gu, Daegu, Korea, Republic of
Goyang-si, Gyeonggi-do, Korea, Republic of
Hwasun-gun, Jeonnam, Korea, Republic of
Gangnam-gu, Seoul, Korea, Republic of
Seodaemun-gu, Seoul, Korea, Republic of
Songpa-gu, Seoul, Korea, Republic of
Sponsors and Collaborators
SymBio Pharmaceuticals
Investigators
Study Chair: Kensei Tobinai, MD, Ph D National Cancer Center Hospital
  More Information

No publications provided

Responsible Party: Masahiro Furukawa, SymBio Pharmaceuticals Limited
ClinicalTrials.gov Identifier: NCT01118845     History of Changes
Other Study ID Numbers: 2010001
Study First Received: May 1, 2010
Results First Received: March 27, 2013
Last Updated: May 29, 2013
Health Authority: Japan: Pharmaceutical and Medical Devices Agency

Keywords provided by SymBio Pharmaceuticals:
Non-Hodgkin's lymphoma
Lymphoma, Large B-Cell
Diffuse, Mantle cell lymphoma, Lymphoma
Follicular, Lymphoma
Large B-Cell, Diffuse

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine
Rituximab
Nitrogen Mustard Compounds
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 24, 2014