A Study of Bendamustine in the Treatment of Chinese Participants With Indolent Non-Hodgkin Lymphoma Refractory to Rituximab Treatment
Condition: Non-Hodgkin Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Bendamustine hydrochloride
Intervention description: Bendamustine will be be administered per dose and schedule specified in the arm description.
Intervention MeSH terms: Bendamustine Hydrochloride
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Bendamustine hydrochloride; CEP-18083; Treanda®; Non-Hodgkin Lymphoma

Summary:

      The primary objective of the study is to determine the overall response rate (ORR), which
      includes complete response (CR) and partial response (PR), to bendamustine treatment in
      participants with indolent non-Hodgkin lymphoma (NHL) that has progressed after rituximab or
      a rituximab-containing therapy.
    

Eligibility criteria:

        Inclusion Criteria:

        - The participant has documented relapse from indolent B-cell NHL. Participants with the
        following subtypes of indolent NHL are eligible for this study: i) small lymphocytic
        lymphoma (peripheral B cell count <5000 cells/cubic millimeters [mm^3]) ii)
        lymphoplasmacytic lymphoma iii) splenic marginal zone B-cell lymphoma (±villous
        lymphocytes) iv) extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid
        tissue type v) nodal marginal zone lymphoma (±monocytoid B-cells) vi) follicle center
        lymphoma vii) follicular (grade 1, 2, or 3a) lymphoma

        - The participant has disease documented to have progressed despite rituximab treatment.
        The participant's disease is considered to be rituximab refractory if any of the following
        criteria are met at any time during the participant's treatment history (progression must
        be documented by computed tomography [CT] scan or magnetic resonance imaging [MRI] or
        biopsy) or if a participant has palpable lymph nodes that were well documented in size and,
        after rituximab treatment, palpable disease remains or comes back [CT, MRI, or biopsy is
        preferred and performed whenever possible to document progressive disease (PD)]: i)
        rituximab-only regimen: Participants who receive a full course of single-agent rituximab
        (at least 2 doses of 375 mg/m^2 [or a therapeutically-active dose] weekly) and have no
        response (do not obtain a PR or better) to treatment or progress after a full regimen of
        rituximab was given.

        ii) rituximab maintenance therapy or extended schedule: Participants who have a history of
        a full course of rituximab (at least 2 doses of 375 mg/m^2 [or a therapeutically-active
        dose] as a single agent [weekly] or in combination with chemotherapy [day 1 of each of 4
        cycles]) and are on a maintenance regimen, and progress before the next scheduled rituximab
        dose or after completing a maintenance rituximab regimen.

        iii) rituximab-chemotherapy combination regimen: Participants who receive a full course of
        rituximab (at least 2 doses of 375 mg/m^2 or a therapeutically-active dose [on day 1 of
        each of 2 cycles]) in combination with chemotherapy and have no response (do not obtain a
        PR or better) to treatment or progress after the last dose of rituximab in a regimen.

        iv) full rituximab exposure treatment: Participants who have a history of a full course of
        rituximab treatment (at least 2 doses of 375 mg/m^2 [or a therapeutically-active dose] as a
        single agent or in combination with chemotherapy) and, in a subsequent
        rituximab/chemotherapy combination regimen, have no response (do not obtain a PR or better)
        to treatment or progress after the last dose of rituximab in a given regimen, even if the
        subsequent regimen included less than 2 doses of rituximab. Participants could receive
        additional systemic treatment after the qualifying rituximab regimen.

          -  The participant has received treatment with at least 1, but no more than 3, previous
             chemotherapy regimens. A regimen is defined as a new treatment combination or agent.
             Retreatment with the identical regimen or agent does not count as a new regimen;
             however, change from cyclophosphamide, vincristine, and prednisolone (CVP) to
             cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is counted as a
             new regimen. Rituximab, radioimmunotherapy, or other biologic treatments not combined
             with chemotherapy are not counted as a regimen.

          -  The participant has a bidimensionally measurable disease with at least 1 lesion
             measuring 2.0 centimeters (cm) or more in a single dimension. Participants who have
             previous involved-field irradiation can be included, provided the irradiated area is
             not the only source of measurable disease.

          -  The participant has a World Health Organization (WHO) performance status of 0, 1, or
             2.

          -  The participant has absolute neutrophil count (ANC) 1000 cells/mm^3 or more and
             platelet count 85000 cells/mm^3 or more.

          -  The participant has a creatinine clearance of more than 30 mL/min as determined by the
             Cockcroft-Gault calculation.

          -  The participant has adequate hepatic function (no more than 2.5 times the upper limit
             of normal (ULN) for aspartate aminotransferase (AST) and alanine aminotransferase
             (ALT), and no more than 1.5 times the upper limit of the normal range (ULN) for total
             bilirubin). Participants with nonclinically significant elevations of bilirubin due to
             Gilbert's disease are eligible.

          -  The participant has had a bone marrow biopsy within 6 weeks before the 1st dose of
             bendamustine.

          -  Women of childbearing potential (not surgically sterile or 1 year postmenopausal) must
             use a medically accepted method of contraception and must agree to continue use of
             this method starting 2 weeks before the start of study drug treatment, during study
             drug treatment, and for 3 months after the end of study drug treatment. Acceptable
             methods of contraception include abstinence, barrier method with spermicide,
             intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted,
             and injected) in conjunction with a barrier method.

          -  Women of childbearing potential must have a negative serum or urine pregnancy test.

          -  Men not surgically sterile or who are capable of producing offspring must practice
             abstinence or use a barrier method of birth control, and must agree to continue use of
             this method starting 2 weeks before the start of study drug treatment, during study
             drug treatment, and for 3 months after the end of study drug treatment.

          -  The participant has an estimated life expectancy of at least 3 months.

          -  The participant (or participant's legal representative) provides written informed
             consent.

        Exclusion Criteria:

          -  The participant has received previous radiotherapy, radioimmunotherapy, chemotherapy,
             or immunotherapy within 4 weeks before day 1 of cycle 1 or has failed to recover (to
             Common Terminology Criteria for Adverse Events [CTCAE] toxicity grade 1 or 2) from
             clinically significant nonhematologic adverse events due to any agents administered
             previously.

          -  The participant has received treatment with an investigational agent within 4 weeks of
             day 1 of cycle 1.

          -  The participant has received hematopoietic growth factors within 4 weeks of day 1 of
             cycle 1. However, participants receiving chronic erythropoietin treatment are eligible
             for inclusion in this study.

          -  The participant has a history of previous high-dose chemotherapy with allogeneic stem
             cell support (history of autologous stem cell support is permissible).

          -  The participant is receiving or has received treatment with therapeutic doses of
             systemic steroids within 4 weeks of day 1 of cycle 1. (Low doses of chronic steroids
             [prednisone or equivalent] up to 20 mg/day for non-neoplastic disorders or for
             indications other than lymphoma or lymphoma-related complications are permitted.)

          -  The participant has transformed disease.

          -  The participant has any history of central nervous system (CNS) or leptomeningeal
             lymphoma.

          -  The participant has, or has had within the past 5 years, an active malignancy other
             than the target cancer. The exceptions are prostate cancer (Gleason grade <6 with
             prostate specific antigen [PSA] levels within the normal range), in situ cervical or
             breast carcinoma, and nonmelanoma skin cancer that have received definitive treatment.

          -  The participant is a pregnant or lactating woman. (Any women becoming pregnant during
             the study will be withdrawn from the study immediately.)

          -  The participant has a serious infection, medical condition, or psychiatric condition
             that, in the opinion of the investigator, might interfere with the achievement of the
             study objectives.

          -  The participant is known to be positive for human immunodeficiency virus (HIV), have
             active hepatitis B, or active hepatitis C (anti-hepatitis C virus [HCV] positive).
             Hepatitis B surface antigen must be tested. The determination of active disease is
             left up to the Investigator.

          -  The participant has a known hypersensitivity to mannitol.

          -  The participant has used bendamustine previously.