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

Phase II Clinical 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 (Multicenter, Open-label).

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.

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