Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Bendamustine Hydrochloride

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

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.

SyB L-0501

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.

Kensei Tobinai, MD, Ph D

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.

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 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

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

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

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

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

SymBio Pharmaceuticals

Masahiro Furukawa

SyB L-0501 was administered in combination with rituximab. SyB L-0501 was administered 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. Rituximab was administered 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.

Age Continuous

20-29 years

30-39 years

40-49 years

50-59 years

60-69 years

70-75 years

Age, Customized

<65 years

≥65 years

Male

Female

Sex/Gender, Customized

Diagnosis of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Stage I

Stage I-E

Stage II

Stage II-E

Stage III

Stage III-S

Stage III-E

Stage III-SE

Stage IV

Unknown

The criteria for Clinical Stage (Ann Arbor staging) are as below:

I: involvement of a single nodal region. II: involvement of 2 or more lymph node regions on the same side of the diaphragm. III: involvement of lymph node regions on both sides of the diaphragm. IV: disseminated involvement of 1 or more extra-lymphatic sites with or without associated lymph node involvement

E: if accompanied by localized involvement of a extra-lymphatic organ or site. S: if accompanied by involvement of the spleen. SE: if both S and E

Clinical Stage (Ann Arbor staging)

Asymptomatic

Symptomatic

Systemic symptoms (B symptoms) (Ann Arbor staging)

Medical history of diffuse large B-cell lymphoma (DLBCL)

Complications of DLBCL

Prior medication/therapy for DLBCL

Prior medication/therapy for DLBCL (Transplant)

Prior treatment for DLBCL

Number of regimens

P.S.(ECOG) criteria are as below:

0: Fully active, able to carry on all pre-disease performance without restriction. 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2: Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours. 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours. 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair

P.S.(performance status)[the Eastern Cooperative Oncology Group (ECOG) criteria]

<5 cm

≥5 cm

Tumor diameter

<7 cm

≥7 cm

Within normal range

Elevated

The normal ranges vary among institutions.

lactate dehydrogenase (LDH)

<240 IU/L

≥240 IU/L

<4 nodular sites

≥4 nodular sites

Site of disease

<2 extranodular sites

≥4 extranodular sites

Positive

Negative

Indeterminate

Bone marrow involvement

Responder

Non-Responder

Response to prior treatment

<12 months

≥12 months

Time from the initiation of prior treatment to the initiation of the study drug in subjects with 1 regimen of prior treatment (64.4% of all the subjects).

Time from prior treatment

Low (score=0-1)

Low-Intermediate (score=2)

High-Intermediate (score=3)

High(score=4-5)

The criteria for International Prognostic Index risk category are as below:

Low (score=0-1): 5-year survival of 73%. Low (score=2): 5-year survival of 51%. High-intermediate (score=3): 5-year survival of 43%. High (score=4-5): 5-year survival of 26%

International Prognostic Index risk category

Low-Intermediate (score<3)

High-Intermediate (score≥3)

Height

Weight

Body Surface Area（BSA）

Toshihiko Nagase

The Overall Response Rate [Complete Response (CR) + Partial Response (PR)] Determined on the Basis of Revised Response Criteria for Malignant Lymphoma

The Complete Response (CR) Rate Determined on the Basis of Revised Response Criteria for Malignant Lymphoma

Progression Free Survival (PFS)

Subjects with adverse event

Subjects with serious adverse event

Number of Subjects With Adverse Event

Adverse events

Serious adverse events

Number of Adverse Events

Subjects with grade 3 abnormality

Subjects with grade 4 abnormality

Number of Subjects With Abnormality (Grade ≥3) in Laboratory Test Values

Subjects with grade 3 Physical Findings

Subjects with grade 4 Physical Findings

Number of Subjects With Grade ≥3 Physical Examination Finding

concomitant medications for adverse events

concomitant medications for complications

concomitant medications for supportive therapy

concomitant medications for other reasons

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

Overall Study

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Anti-Infective Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Dyskinesia Agents

Micronutrients

Hematinics

Vitamins

Carboplatin

Dexamethasone

Etoposide

Cytarabine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Methotrexate

Prednisone

Vincristine

Ifosfamide

Dexamethasone acetate

Etoposide phosphate

Vinblastine

Trimethoprim, Sulfamethoxazole Drug Combination

Isophosphamide mustard

Trimethoprim

Sulfamethoxazole

Immunosuppressive Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antimetabolites

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Antiviral Agents

Tubulin Modulators

Antimitotic Agents

Antimalarials

Antiprotozoal Agents

Antiparasitic Agents

Folinic Acid

Folate

Vitamin B9

See Detailed Description section for details of treatment interventions.

Doxorubicin, Cotrimoxazole, Carboplatin, Ifosfamide, Dexamethasone, Prednisone, Vincristine, Cytarabine, Methotrexate, Etoposide, Cyclophosphamide, Vinblastine

Stem cell transplant,

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of SyB L-0501 in Combination With Rituximab to Treat Relapsed/Refractory Diffuse Large B-Cell Lymphoma	NCT01118845	Non-Hodgkin's L... Lymphoma, Large... Diffuse, Mantle... Follicular Lymp... Large B-Cell, D...	SyB L-0501 Rituximab	20 Years - 75 Years	SymBio Pharmaceuticals
Large Cell Lymphoma Pilot Study III	NCT00187070	Lymphoma, Large... Lymphoma, Non-H...	Doxorubicin, Co... Stem cell trans... Radiation Thera...	- 18 Years	St. Jude Children's Research Hospital
Large Cell Lymphoma Pilot Study III	NCT00187070	Lymphoma, Large... Lymphoma, Non-H...	Doxorubicin, Co... Stem cell trans... Radiation Thera...	- 18 Years	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for lymphoma, large cell