A Study on Pharmacokinetics (PK), Efficacy and Safety of Subcutaneous (SC) Versus Intravenous (IV) Rituximab, in Combination With CHOP (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) in Previously Untreated Participants With CD20 Positive Diffuse Large B-Cell Lymphoma (DLBCL)
Condition: Lymphoma, Large B-Cell, Diffuse
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Intervention: Rituximab IV; Rituximab SC; Rituximab IV; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone; Paracetamol; Diphenhydramine hydrochloride or alternative antihistamine
Intervention description: Rituximab will be administered intravenously through Cycle 1-8 at a standard dose of 375 mg/m^2 (milligram per square meter).; Rituximab will be administered subcutaneously through Cycle 2-8 at a dose of 1400 milligram (mg).; Rituximab will be administered intravenously in Cycle 1 at a standard dose of 375 mg/m^2.; Cyclophosphamide will be administered IV at a dose of 750 mg/m^2; Doxorubicin will be administered IV at a dose of 50 mg/m^2; Vincristine will be administered IV at a dose of 1.4 mg/m^2; Prednisone will be administered orally at a dose of 100 mg/day; All participants are required to receive 1000 mg oral paracetamol as premedication prior to starting each infusion of rituximab; All participants are required to receive 50-100 mg oral diphenhydramine hydrochloride or alternative antihistamine as premedication prior to starting each infusion of rituximab
Intervention MeSH terms: Diphenhydramine; Promethazine; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Vincristine; Histamine H1 Antagonists; Histamine Antagonists
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Mabthera, Rituximab, SC, Subcutaneous, DLBCL

Summary:

      This is a multicenter China-only study to investigate the PK, efficacy and safety of SC
      rituximab versus IV rituximab, both in combination with CHOP (cyclophosphamide, doxorubicin,
      vincristine, prednisone) in previously untreated participants with CD20 positive DLBCL.
      Participants will be randomized to receive eight cycles of rituximab SC or rituximab IV
      combined with six or eight cycles of standard CHOP chemotherapy. After the end of study
      treatment, participants will be followed-up every 3 months for 6 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Previously untreated CD20 positive diffuse large B-cell lymphoma (DLBCL)

          -  Participants with an International Prognostic Index (IPI) score of 1 to 5 or IPI score
             of 0 with bulky disease, defined as one lesion >/=7.5 cm

          -  At least one bi-dimensionally measurable lesion defined as >/=1.5 cm in its largest
             dimension on CT scan

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Left ventricular ejection fraction (LVEF) >/=50% on cardiac multiple-gated acquisition
             (MUGA) scan or cardiac echocardiogram

          -  A negative serum pregnancy test or a negative urine pregnancy test within 7 days prior
             to study treatment

          -  For men who are not surgically sterile, agreement to use a barrier method of
             contraception during the treatment period and until >/=12 months after the last dose
             of rituximab SC or rituximab IV or according to institutional guidelines for CHOP
             chemotherapy, whichever is longer, and agreement to request that their partners use an
             additional method of contraception

          -  For women of reproductive potential who are not surgically sterile, agreement to use
             adequate methods of contraception during the treatment period and until >/=12 months
             after the last dose of rituximab SC or rituximab IV or according to institutional
             guidelines for CHOP chemotherapy, whichever is longer

          -  Adequate hematologic function confirmed within 14 days prior to randomization

        Exclusion Criteria:

          -  Transformed non-Hodgkin's lymphoma (NHL) or types of NHL other than DLBCL and its
             subtypes according to World Health Organization classification

          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
             antibodies or known sensitivity or allergy to murine products

          -  Contraindication to any of the individual components of CHOP, including prior receipt
             of anthracyclines

          -  Prior therapy for DLBCL, with the exception of nodal biopsy or local irradiation or
             surgery for diagnosis

          -  Prior treatment with cytotoxic drugs or rituximab for another condition
             (e.g.,rheumatoid arthritis) or prior use of an anti-CD20 antibody

          -  Current or recent treatment with another investigational drug or participation in
             another investigational therapeutic study

          -  Ongoing corticosteroid use (>30 mg/day of prednisone or equivalent)

          -  Primary CNS lymphoma, blastic variant of mantle cell lymphoma, or histologic evidence
             of transformation to a Burkitt lymphoma, primary mediastinal DLBCL, primary effusion
             lymphoma, and primary cutaneous DLBCL

          -  History of other malignancy that could affect compliance with the protocol or
             interpretation of results

          -  Evidence of significant, uncontrolled concomitant diseases including but not limited
             to significant cardiovascular disease or pulmonary disease

          -  Any of the following abnormal laboratory values: creatinine >1.5 upper limit of normal
             (ULN), aspartate aminotransferase (AST) / alanine aminotransferase (ALT) >2.5ULN,
             total bilirubin >1.5ULN, prothrombin time - international normalized ratio (PT-INR) /
             partial thromboplastin time (PTT) / activated partial thromboplastin time
             (aPTT)>1.5ULN

          -  Positive test results for chronic hepatitis B (HBV) and or hepatitis C (HCV)
             infection; Participants with occult or prior HBV infection (defined as negative HBsAg
             and positive total hepatitis B core antibody [HBcAb]) may be included if HBV DNA is
             undetectable; Participants positive for HCV antibody are eligible only if polymerase
             chain reaction (PCR) is negative for HCV RNA

          -  Known history of human immunodeficiency virus (HIV)