For SyB L-0501RI administered by an intravenous rapid infusion in combination with rituximab,
the safety will be investigated in previously untreated patients with low-grade B-cell
non-Hodgkin's lymphoma (Lg-B-NHL) or mantle cell lymphoma (MCL), and the safety and
tolerability will be investigated in patients with recurrent/refractory diffuse large B-cell
lymphoma (DLBCL).
For previously untreated patients with Lg-B-NHL or MCL
Inclusion Criteria
Patients who satisfy all of the conditions listed below:
▪ Patients who satisfy all of the following criteria A) to D): A) Patients who are
histopathologically confirmed to have one of the following subtypes of CD20 (cluster of
differentiation 20)-positive Lg-B-NHL or MCL (excluding transformed lymphoma) by lymph node
biopsy or evaluable tissue biopsy (World Health Organization [WHO] histological
classification [4th edition]).
- Small lymphocytic lymphoma
- Splenic marginal zone lymphoma
- Lymphoplasmacytic lymphoma
- Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT)
- Nodal marginal zone lymphoma
- Follicular lymphoma (Grade 1, 2, 3a)
- MCL B) Patients who have at least one measurable lesion (>1.5 cm in major axis on
computed tomography [CT]).
C) Patients without a history of treatment for lymphoma. D) Patients with at least one of
the following clinical signs or symptoms (with the exception of MCL patients).
1. Bulky disease >7 cm in major axis on CT (excluding lesions in the spleen)
2. B symptoms
- Unexplained fever exceeding 38.0ºC
- Night sweats
- Weight loss of more than 10% within 6 months before registration
3. Elevated serum lactate dehydrogenase (LDH) or β2-microglobulin level
4. Involvement of at least 3 regional lymph nodes >3 cm in major axis on CT
5. Symptomatic splenomegaly
6. Compressive symptoms
7. Pleural effusion and/or ascites
- Patients aged between 20 and 79 years (at the time of registration).
- Patients who are expected to survive for at least 3 months.
- Patients with an Eastern Cooperative Oncology Group (ECOG) performance status
(PS) of 0 to 2.
- Patients with adequate functional reserve of major organs (bone marrow, heart,
lungs, liver, kidneys, etc.).
- Neutrophil count: ≥1,500/mm^3
- Platelet count: ≥75,000/mm^3
- Aspartate aminotransferase (AST) [glutamic oxaloacetic transaminase [GOT]):
≤3.0 times the institution's upper limit of normal (ULN)
- Alanine aminotransferase (ALT) [glutamic pyruvic transaminase (GPT)]: ≤3.0
times the institution's ULN
- Total bilirubin: <2.0 mg/dL
- Serum creatinine: <2.0 mg/dL
- Percutaneous arterial oxygen saturation (SpO2): ≥95% or Partial arterial
oxygen pressure (PaO2): ≥65 mmHg
- No abnormal findings requiring treatment on electrocardiogram (ECG)
- Left ventricular ejection fraction (LVEF) on echocardiography: ≥55%
- Patients who have provided written informed consent to participate in this study.
Exclusion Criteria
Patients who meet any of the following conditions will be excluded:
- MCL patients aged ≤65 years (at the time of registration).
- Patients who have a history of treatment for Lg-B-NHL or MCL (chemotherapy,
radiotherapy, antibody therapy or antitumor steroid therapy).
- Patients who have previously received hematopoietic stem cell transplantation.
- Patients with invasion to central nervous system (CNS) or clinical symptoms suspected
of CNS invasion.
- Patients with serious active infection (requiring antibiotic, antifungal, or antiviral
IV injection).
- Patients with serious complications (such as hepatic failure and renal failure).
- Patients with concurrent or previous, serious cardiac disease (e.g., myocardial
infarction, ischemic heart disease); however, patients with arrhythmias are allowed to
be enrolled if it does not require treatment at the time of registration.
- Patients with serious gastrointestinal symptoms (such as high-grade or severe
nausea/vomiting or diarrhea).
- Patients with malignant pleural effusion, pericardial effusion, or ascites.
- Patients positive for hepatitis B surface (HBs) antigen, hepatitis C virus (HCV)
antibody, or human immunodeficiency virus (HIV) antibody (patients with positive
hepatitis B virus [HBV]-DNA quantitative test results if they are negative for HBs
antigen and positive for HBs antibody or hepatitis B core [HBc] antibody).
- Patients with serious bleeding tendencies (such as disseminated intravascular
coagulation [DIC]).
- Patients with a fever of 38.0ºC or higher (with the exception of fever developing as a
B symptom).
- Patients with concurrent or previous interstitial pneumonia, pulmonary fibrosis, or
chronic obstructive pulmonary disease.
- Patients with active multiple primary cancers or patients with a history of other
malignancy within the past 5 years, with the exception of basal cell carcinoma or
squamous cell carcinoma of the skin or carcinoma in situ of the cervix or digestive
organs.
- Patients with concurrent or previous autoimmune hemolytic anemia.
- Patients who have previously received bendamustine hydrochloride.
- Patients who have received a cytokine preparation, such as granulocyte colony-
stimulating factor (G-CSF) or erythropoietin, or blood transfusions within 2 weeks
before a screening test for this study.
- Patients who have received other investigational products or unapproved drugs within 3
months before registration for this study.
- Patients with a history of allergy to medications similar to SyB L-0501RI (e.g.,
alkylating agents and purine-nucleoside derivatives).
- Patients who cannot tolerate rituximab.
- Pregnant, possibly pregnant, or lactating women.
- Patients, whether male or female, who do not agree to use contraception.
Duration:
Male patients; during the treatment period and for 6 months after treatment Female patients
with no menstruation; during the treatment period Female patients with menstruation; during
the treatment period and for 3 months after treatment
- Patients with drug addiction, narcotic addiction, or alcohol dependence.
- Patients who are unable to take pre-treatment medication due to drug allergies or the
like.
- Patients who are otherwise judged by the investigator or subinvestigator to be
unsuitable as a subject.
For patients with recurrent or refractory DLBCL
Inclusion Criteria
Patients who satisfy all of the conditions listed below:
▪ Patients who satisfy both of the following criteria A and B: A) Patients who are
histopathologically confirmed to have CD20-positive DLBCL (excluding transformed lymphoma)
by lymph node biopsy or evaluable tissue biopsy (WHO histological classification [4th
edition]).
B) Patients with recurrent or refractory DLBCL who have had disease progression after
standard rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisolone
(R-CHOP) therapy or R-CHOP-like therapy as first-line treatment.
- Patients aged between 20 and 79 years (at the time of registration).
- Patients who are expected to survive for at least 3 months.
- Patients with an ECOG PS of 0 to 2.
- Patients with adequate functional reserve of major organs (bone marrow, heart, lungs,
liver, kidneys, etc.).
- Neutrophil count: ≥1,500/mm^3
- Platelet count: ≥75,000/mm^3
- AST (GOT): ≤3.0 times the institution's ULN
- ALT (GPT): ≤3.0 times the institution's ULN
- Total bilirubin: <2.0 mg/dL
- Serum creatinine: <2.0 mg/dL
- SpO2: ≥95% or PaO2: ≥65 mmHg
- No abnormal findings requiring treatment on ECG
- LVEF on echocardiography: ≥55%
- Patients who have provided written informed consent to participate in this study.
Exclusion Criteria
Patients who meet any of the following conditions will be excluded:
- Patients with an off-treatment interval of less than 3 weeks between the last day of
preceding treatment (chemotherapy, radiotherapy, antibody therapy, or antitumor
steroid therapy) for DLBCL and the day of registration for this study.
- Patients who are judged by the investigator or subinvestigator to be suitable for
autologous peripheral blood stem cell transplantation.
- Patients who have previously received allogeneic hematopoietic stem cell
transplantation.
- Patients who have previously received radioimmunotherapy
- Patients with invasion to CNS or clinical symptoms suspected of CNS invasion.
- Patients with serious active infection (requiring antibiotic, antifungal, or antiviral
IV injection).
- Patients with serious complications (such as hepatic failure and renal failure).
- Patients with concurrent or previous, serious cardiac disease (e.g., myocardial
infarction, ischemic heart disease); however, patients with arrhythmias are allowed to
be enrolled if it does not require treatment at the time of registration.
- Patients with serious gastrointestinal symptoms (such as high-grade or severe
nausea/vomiting or diarrhea).
- Patients with malignant pleural effusion, pericardial effusion, or ascites.
- Patients positive for HBs antigen, HCV antibody, or HIV antibody (patients with
positive HBV-DNA quantitative test results if they are negative for HBs antigen and
positive for HBs antibody or HBc antibody).
- Patients with serious bleeding tendencies (such as DIC).
- Patients with a fever of 38.0ºC or higher (with the exception of fever developing as a
B symptom).
- Patients with concurrent or previous interstitial pneumonia, pulmonary fibrosis, or
chronic obstructive pulmonary disease.
- Patients with active multiple primary cancers or patients with a history of other
malignancy within the past 5 years, with the exception of basal cell carcinoma or
squamous cell carcinoma of the skin or carcinoma in situ of the cervix or digestive
organs.
- Patients with concurrent or previous autoimmune hemolytic anemia.
- Patients who have previously received bendamustine hydrochloride.
- Patients who have received a cytokine preparation, such as G-CSF or erythropoietin, or
blood transfusions within 2 weeks before a screening test for this study.
- Patients who have received other investigational products or unapproved drugs within 3
months before registration for this study.
- Patients with a history of allergy to medications similar to SyB L-0501RI (e.g.,
alkylating agents and purine-nucleoside derivatives).
- Patients who cannot tolerate rituximab.
- Pregnant, possibly pregnant, or lactating women.
- Patients, whether male or female, who do not agree to use contraception.
Duration:
Male patients; during the treatment period and for 6 months after treatment Female patients
with no menstruation; during the treatment period Female patients with menstruation; during
the treatment period and for 3 months after treatment
- Patients with drug addiction, narcotic addiction, or alcohol dependence.
- Patients who are unable to take pre-treatment medication due to drug allergies or the
like.
- Patients who are otherwise judged by the investigator or subinvestigator to be
unsuitable as a subject.
