phase i/ii study of syb l-0501ri in combination with rituximab to treat lymphoma

Conditions: Lymphoma, B-cell, Diffuse

Summary: 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).


Eligibility criteria:
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.

Keywords: lymphoma, b-cell, diffuse, syb l-0501ri