Lymphoma, B-cell, Diffuse
Conditions
Keywords
Lymphoma, B-cell, Diffuse, SyB L-0501RI
Brief 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).
Interventions
DRUGSyB L-0501RI
The specified dose of SyB L-0501RI and rituximab will be administered by intravenous rapid infusion over 10 minutes on specified days.
Sponsors
SymBio Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 79 Years
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events (type, frequency, severity) | Up to 36 weeks |
| Number of subjects with adverse event | Up to 36 weeks |
| Number of adverse events | Up to 36 weeks |
| Number of subjects with abnormality (Common Terminology Criteria for Adverse Events [CTCAE] grade ≥3) in laboratory test values | Up to 36 weeks |
| Number of subjects with grade ≥3 physical examination finding | Up to 36 weeks |
| Number of subjects with dose limiting toxicity in DLBCL arm | Up to 36 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Complete response (CR) rate | Up to 36 weeks |
| The half-life period (T1/2) of unchanged SyB L-0501 | Prior to and 5, 10 min after start of administration, and 5, 15, 30, 60, 120, 240, 360 min after completion of administration on Day 1 of the 1st cycle in Lg-B-NHL or MCL Arm (in DLBCL Arm, Day 2 of the 1st cycle) |
| Overall response rate (antitumor effect : ≥ partial response [PR]) | Up to 36 weeks |
| Progression-free survival (PFS) | Up to 36 weeks |
| The maximum concentration (Cmax) of unchanged SyB L-0501 | Prior to and 5, 10 min after start of administration, and 5, 15, 30, 60, 120, 240, 360 min after completion of administration on Day 1 of the 1st cycle in Lg-B-NHL or MCL Arm (in DLBCL Arm, Day 2 of the 1st cycle) |
| The maximum drug concentration time (Tmax) of unchanged SyB L-0501 | Prior to and 5, 10 min after start of administration, and 5, 15, 30, 60, 120, 240, 360 min after completion of administration on Day 1 of the 1st cycle in Lg-B-NHL or MCL Arm (in DLBCL Arm, Day 2 of the 1st cycle) |
| The area under the curve (AUC) for unchanged SyB L-0501 | Prior to and 5, 10 min after start of administration, and 5, 15, 30, 60, 120, 240, 360 min after completion of administration on Day 1 of the 1st cycle in Lg-B-NHL or MCL Arm (in DLBCL Arm, Day 2 of the 1st cycle) |
Countries
Japan
Outcome results
None listed