Efficacy and Safety Study of SyB L-0501 in Combination With Rituximab in Patients With Untreated, Low-grade B Cell Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma
Condition: Low-grade B Cell Non-Hodgkin's Lymphoma; Mantle Cell Lymphoma Where Hematopoietic Stem Cell Transplantation is Not Indicated
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Mantle-Cell; Lymphoma, B-Cell
Intervention: SyB L-0501; rituximab
Intervention description: A dose of 90 mg/m^2/day of SyB L-0501 is administered on Day 1 and Day 2 as an IV drip infusion, followed by 26-day observation. This is 1 cycle (28 days), which will be repeated for a maximum of 6 times.; A dose of 375 mg/m^2 of rituximab is administered on Day 1 (Day 0 in Cycle 1 only) as an IV drip infusion, followed by 26-day observation. This is 1 cycle (28 days), which will be repeated for a maximum of 6 times. From Cycle 2, rituximab will be coadministered with SyB L-0501 on Day 1. However, if the investigator or sub-investigator judges that the coadministration is difficult, rituximab may be administered on Day 0.
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 20 Years
Maximum age: 79 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to assess the efficacy and safety of SyB L-0501 (two-day
      consecutive 90 mg/m2/day IV drip infusions) in combination with rituximab (375 mg/m2 IV drip
      infusion) on untreated, low-grade B cell non-Hodgkin's lymphoma and mantle cell lymphoma
      where hematopoietic stem cell transplantation is not indicated.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients who are histopathologically confirmed to have the following cluster of
             differentiation 20 (CD20) positive low-grade B cell non-Hodgkin's lymphoma or mantle
             cell lymphoma by lymph node biopsy or evaluable tissue biopsy within 6 months before
             the registration WHO Classification of Tumors (fourth edition):

               -  Small lymphocytic lymphoma

               -  Splenic marginal zone B-cell lymphoma

               -  Lymphoplasmacytic lymphoma

               -  Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
                  (MALT lymphoma)

               -  Nodal marginal zone B-cell lymphoma

               -  Follicular lymphoma (Grade 1, 2, 3a)

               -  Mantle cell lymphoma

          2. Patients with a measurable lesion ( > 1.5 cm in major axis on CT)

          3. Patients without a medical history

          4. Patients with at least 1 of the following clinical symptoms or signs (excluding mantle
             cell lymphoma):

               -  Bulky disease measuring > 7 cm in major axis on CT (excluding spleen)

               -  B symptoms

                    1. Fever exceeding 38.0ºC of unknown cause

                    2. Night sweats

                    3. Weight decrease exceeding 10% within 6 months before patient registration

               -  Elevated serum LDH or beta 2 microglobulin

               -  Three or more regional lymph nodes of > 3 cm in major axis on CT

               -  Symptomatic splenomegaly

               -  Intracranial pressure

               -  Pleural effusion/ascites retention

          5. Patients expected to live for at least 3 months

          6. Patients aged between 20 and 79 years (at the time of registration)

          7. Patients whose Eastern Cooperative Oncology Group (ECOG) performance status (P.S.) is
             0～2

          8. Patients with adequately maintained major organ function (bone marrow, heart, lungs,
             liver, kidneys)

               -  Neutrophil count: not less than 1,500 /mm3

               -  Platelet count: not less than 75,000 /mm3

               -  Aspartate aminotransferase (AST)[Glutamic oxaloacetic transaminase (GOT)]: not
                  more than 3 times the standard upper limit for the site

               -  Alanine aminotransferase (ALT)[Glutamic pyruvic transaminase (GPT)]: not more
                  than 3 times the standard upper limit for the site

               -  Total bilirubin: not more than 1.5 times the standard upper limit for the site

               -  Serum creatinine: not more than 1.5 times the standard upper limit for the site

               -  Arterial partial pressure of oxygen (PaO2): not less than 65 mmHg

               -  Electrocardiogram shows no abnormal findings that require treatment

               -  Echocardiogram of left ventricular ejection fraction (LVEF): not less than 55%

          9. Patients whose informed consent has been obtained in person

        Exclusion Criteria:

        Patients who fall under any one of the following criteria are to be excluded

          1. Patients whose transformation has been confirmed histopathologically

          2. Mantle cell lymphoma patients aged 65 years or younger

          3. Patients who were administered or received transfusion of cytokine formulations such
             as G-CSF (granulocyte colony stimulating factor) and erythropoietin within 14 days
             before pre-registration test

          4. Patients with severe active infectious disorders (receiving antibiotics, antifungals,
             or antivirus IV injection)

          5. Patients with serious complications (such as hepatic or renal failure)

          6. Patients with severe complications of cardiac disease (examples: myocardial
             infarction, ischemic heart disease) or its previous history within 2 years before
             patient registration, and patients with arrhythmia requiring a treatment

          7. Patients with serious gastrointestinal conditions (persistent or severe
             nausea/vomiting or diarrhea)

          8. Patients who are positive for hepatitis B surface (HBs) antigen, hepatitis C virus
             (HCV) antibody or HIV antibody [if HBs or hepatitis B core (HBc) positive, patients
             whose hepatitis B virus (HBV)-DNA test results indicate positive]

          9. Patients with serious bleeding tendencies [such as disseminated intravascular
             coagulation (DIC)]

         10. Patients having or suspected of having symptoms indicative of the central nervous
             system (CNS) involvement

         11. Patients with interstitial pneumonitis, pulmonary fibrosis, pulmonary emphysema
             complications requiring treatment or its medical history.

         12. Patients with active multiple primary cancer

         13. Patients who received chemotherapy, radiotherapy, antibody therapy and antitumor
             steroid therapy in the past

         14. Patients with complications or medical history of autoimmune haemolytic anaemia

         15. Patients who were administered investigative or unapproved drugs within 3 months
             before patient registration

         16. Patients with addiction to drugs or narcotics, or alcoholism

         17. Patients who have previously received hematopoietic stem cell transplantation

         18. Patients who are or may be pregnant, lactating patients

         19. Patients, whether male or female, who do not agree to use contraception

         20. Patients otherwise judged by the investigator or the sub-investigator to be unsuitable
             for inclusion in the study