- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03900377
Phase I/II Study of SyB L-0501RI in Combination With Rituximab to Treat Lymphoma
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
Study Overview
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Katsuhisa Goto
- Phone Number: +81-3-5472-1127
- Email: kgoto.34@symbiopharma.com
Study Contact Backup
- Name: Naoko Takahashi
- Phone Number: +81-3-5472-1127
- Email: ntakahashi.nt03@symbiopharma.com
Study Locations
-
-
-
Akita, Japan
- Research Site
-
Fukuoka, Japan
- Research Site
-
Kagoshima, Japan
- Research Site
-
Kumamoto, Japan
- Research Site
-
Kyoto, Japan
- Research Site
-
Okayama, Japan
- Research Site
-
Yamagata, Japan
- Research Site
-
-
Aichi
-
Nagoya, Aichi, Japan
- Research Site
-
-
Gunma
-
Ōta, Gunma, Japan
- Research Site
-
-
Hokkaido
-
Sapporo, Hokkaido, Japan
- Research Site
-
-
Hyogo
-
Kobe, Hyogo, Japan
- Research Site
-
-
Kanagawa
-
Isehara, Kanagawa, Japan
- Research Site
-
-
Okayama
-
Kurashiki, Okayama, Japan
- Research Site
-
-
Tokyo
-
Koto-ku, Tokyo, Japan
- Research Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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).
- Bulky disease >7 cm in major axis on CT (excluding lesions in the spleen)
B symptoms
- Unexplained fever exceeding 38.0ºC
- Night sweats
- Weight loss of more than 10% within 6 months before registration
- Elevated serum lactate dehydrogenase (LDH) or β2-microglobulin level
- Involvement of at least 3 regional lymph nodes >3 cm in major axis on CT
- Symptomatic splenomegaly
- Compressive symptoms
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Lg-B-NHL or MCL
For previously untreated patients with Lg-B-NHL or MCL, rituximab will be intravenously administered at 375 mg/m^2 on Day 0 (the day before Day 1 only in Cycle 1), and SyB L-0501RI will be intravenously administered at 90 mg/m^2/day on Day 1 and Day 2 of each 28-day cycle with up to 6 cycles.
|
The specified dose of SyB L-0501RI and rituximab will be administered by intravenous rapid infusion over 10 minutes on specified days.
Other Names:
|
Experimental: DLBCL
For patients with recurrent or refractory DLBCL, rituximab will be intravenously administered at 375 mg/m^2 on Day 1, and SyB L-0501RI will be intravenously administered at 120 mg/m^2/day on Day 2 and Day 3 of each 21-day cycle with up to 6 cycles.
|
The specified dose of SyB L-0501RI and rituximab will be administered by intravenous rapid infusion over 10 minutes on specified days.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Adverse events (type, frequency, severity)
Time Frame: Up to 36 weeks
|
Up to 36 weeks
|
Number of subjects with adverse event
Time Frame: Up to 36 weeks
|
Up to 36 weeks
|
Number of adverse events
Time Frame: Up to 36 weeks
|
Up to 36 weeks
|
Number of subjects with abnormality (Common Terminology Criteria for Adverse Events [CTCAE] grade ≥3) in laboratory test values
Time Frame: Up to 36 weeks
|
Up to 36 weeks
|
Number of subjects with grade ≥3 physical examination finding
Time Frame: Up to 36 weeks
|
Up to 36 weeks
|
Number of subjects with dose limiting toxicity in DLBCL arm
Time Frame: Up to 36 weeks
|
Up to 36 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Complete response (CR) rate
Time Frame: Up to 36 weeks
|
Up to 36 weeks
|
Overall response rate (antitumor effect : ≥ partial response [PR])
Time Frame: Up to 36 weeks
|
Up to 36 weeks
|
Progression-free survival (PFS)
Time Frame: Up to 36 weeks
|
Up to 36 weeks
|
The maximum concentration (Cmax) of unchanged SyB L-0501
Time Frame: 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)
|
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
Time Frame: 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)
|
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
Time Frame: 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)
|
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 half-life period (T1/2) of unchanged SyB L-0501
Time Frame: 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)
|
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)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, B-Cell
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- 2018001 (Sun Yat-Sen University)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Lymphoma, B-cell, Diffuse
-
Qian WenbinNot yet recruitingDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaChina
-
National Cancer Institute (NCI)WithdrawnDiffuse, Large B-cell Lymphoma | Lymphoma, Diffuse Large-Cell | Lymphoma, Diffuse Large-Cell B-cell | Large-Cell Lymphoma, Diffuse
-
University Hospital Southampton NHS Foundation...Hoffmann-La RocheTerminatedDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaUnited Kingdom
-
Dana-Farber Cancer InstituteBayer; AbbVieActive, not recruitingDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); AmgenActive, not recruitingRecurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | CD20 Positive | Stage I Diffuse Large B-Cell Lymphoma | Stage II Diffuse Large B-Cell Lymphoma | Stage III Diffuse Large B-Cell Lymphoma | Stage IV Diffuse Large B-Cell LymphomaUnited States
-
Memorial Sloan Kettering Cancer CenterRecruitingLymphoma | Lymphoma, B-Cell | DLBCL - Diffuse Large B Cell Lymphoma | Large B-cell Lymphoma | Large-cell Lymphoma | Mediastinal B-Cell Diffuse Large Cell LymphomaUnited States
-
Memorial Sloan Kettering Cancer CenterSanofi; Columbia University; Medical College of Wisconsin; University of Rochester and other collaboratorsActive, not recruitingDiffuse Large B-cell Lymphoma (DLBCL) | Relapsed Diffuse Large B-cell Lymphoma (DLBCL) | Refractory Diffuse Large B-cell Lymphoma (DLBCL)United States
-
Autolus LimitedCompletedDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | DLBCL | Relapsed Diffuse Large B-Cell LymphomaUnited States, United Kingdom
-
Herlev HospitalOdense University Hospital; Zealand University Hospital; Aarhus University Hospital and other collaboratorsCompletedDiffuse Large B-cell Lymphoma Recurrent | Diffuse Large B Cell Lymphoma | Diffuse Large B-Cell Lymphoma Cell of Origin
-
NeoImmuneTechRecruitingRecurrent Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified | Refractory High Grade B-Cell Lymphoma | Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma | Refractory Diffuse Large B-cell LymphomaUnited States
Clinical Trials on SyB L-0501RI
-
SymBio PharmaceuticalsCompletedChronic Lymphocytic LeukemiaJapan
-
SymBio PharmaceuticalsCompletedRelapsed/Refractory Multiple MyelomaJapan
-
SymBio PharmaceuticalsCompleted
-
SymBio PharmaceuticalsCompleted
-
SymBio PharmaceuticalsCompletedRadiotherapy-induced Nausea and Vomiting (RINV)Japan
-
SymBio PharmaceuticalsCompletedLow-grade B Cell Non-Hodgkin's Lymphoma | Mantle Cell Lymphoma Where Hematopoietic Stem Cell Transplantation is Not IndicatedJapan
-
SymBio PharmaceuticalsTerminated
-
Samyang Biopharmaceuticals CorporationCompletedNasolabial FoldsKorea, Republic of
-
Samyang Biopharmaceuticals CorporationNot yet recruiting
-
Onconova Therapeutics, Inc.CompletedMyelodysplastic Syndromes | Chronic Myelomonocytic Leukemia | Cytopenia | Refractory Anemia With Excess BlastsUnited States, Australia, Spain, Italy, Germany, France, Sweden, Denmark