Clinical Trials /

Phase I/II Study of SyB L-0501RI in Combination With Rituximab to Treat Lymphoma

NCT03900377

Description:

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).

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Nodal Marginal Zone Lymphoma
  • Small Lymphocytic Lymphoma
  • Splenic Marginal Zone Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase I/II Study of SyB L-0501RI in Combination With Rituximab to Treat Lymphoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2018001
  • NCT ID: NCT03900377

Conditions

  • Lymphoma, B-cell, Diffuse

Interventions

DrugSynonymsArms
SyB L-0501RIRituximabLg-B-NHL or MCL

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Lg-B-NHL or MCLExperimentalFor 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.
  • SyB L-0501RI
DLBCLExperimentalFor 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.
  • SyB L-0501RI

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.
      
Maximum Eligible Age:79 Years
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events (type, frequency, severity)
Time Frame:Up to 36 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Complete response (CR) rate
Time Frame:Up to 36 weeks
Safety Issue:
Description:
Measure:Overall response rate (antitumor effect : ≥ partial response [PR])
Time Frame:Up to 36 weeks
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:Up to 36 weeks
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:SymBio Pharmaceuticals

Trial Keywords

  • Lymphoma, B-cell, Diffuse, SyB L-0501RI

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