Lymphoma, B-cell, Diffuse Clinical Trial
Official title:
A Multicenter, Open-label, Phase I/II Study to Investigate the Safety and Tolerability of SyB L-0501RI (Bendamustine Hydrochloride for Injection) Administered As an Intravenous (IV) Rapid Infusion Over 10 Minutes
| Verified date | June 2023 |
| Source | SymBio Pharmaceuticals |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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).
| Status | Completed |
| Enrollment | 37 |
| Est. completion date | February 26, 2021 |
| Est. primary completion date | September 9, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 20 Years to 79 Years |
| Eligibility | 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 ß2-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. |
| Country | Name | City | State |
|---|---|---|---|
| Japan | Research Site | Akita | |
| Japan | Research Site | Fukuoka | |
| Japan | Research Site | Isehara | Kanagawa |
| Japan | Research Site | Kagoshima | |
| Japan | Research Site | Kobe | Hyogo |
| Japan | Research Site | Koto-ku | Tokyo |
| Japan | Research Site | Kumamoto | |
| Japan | Research Site | Kurashiki | Okayama |
| Japan | Research Site | Kyoto | |
| Japan | Research Site | Nagoya | Aichi |
| Japan | Research Site | Okayama | |
| Japan | Research Site | Ota | Gunma |
| Japan | Research Site | Sapporo | Hokkaido |
| Japan | Research Site | Yamagata |
| Lead Sponsor | Collaborator |
|---|---|
| SymBio Pharmaceuticals |
Japan,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Adverse events (type, frequency, severity) | Up to 36 weeks | ||
| Primary | Number of subjects with adverse event | Up to 36 weeks | ||
| Primary | Number of adverse events | Up to 36 weeks | ||
| Primary | Number of subjects with abnormality (Common Terminology Criteria for Adverse Events [CTCAE] grade =3) in laboratory test values | Up to 36 weeks | ||
| Primary | Number of subjects with grade =3 physical examination finding | Up to 36 weeks | ||
| Primary | Number of subjects with dose limiting toxicity in DLBCL arm | Up to 36 weeks | ||
| Secondary | Complete response (CR) rate | Up to 36 weeks | ||
| Secondary | Overall response rate (antitumor effect : = partial response [PR]) | Up to 36 weeks | ||
| Secondary | Progression-free survival (PFS) | Up to 36 weeks | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) |