A Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent Lymphoma
Condition: B-cell Small Lymphocytic Lymphoma Recurrent
MeSH terms: Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: TRU-016; Bendamustine; Rituximab
Intervention description: 100 mg TRU-016 lyophilized solution for infusion at 10 or 20 mg/kg (or 6 mg/kg, if necessary) on Days 1 and 15 of each 28 day cycle; Bendamustine by IV administration on Days 1 and 2 of each 28 day cycle.; Rituximab by IV administration at 375 mg/m^2 on Day 2 of each 28 day cycle.
Intervention MeSH terms: Rituximab; Bendamustine Hydrochloride
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: follicular lymphoma; small lymphocytic lymphoma; marginal zone lymphoma; non-Hodgkin's lymphoma; indolent lymphoma

Summary:

      This was a Phase 1 multicenter study of bendamustine, rituximab and TRU-016 (BRT) in subjects
      with relapsed indolent B-cell lymphoma. This was a multiple-dose escalation study to
      determine the maximum-tolerated dose (MTD) of TRU-016 given in combination with rituximab and
      bendamustine and to determine a safe dosing regimen for the combination in up to 12 subjects
      with relapsed indolent lymphoma.

      The originally planned Phase 2 portion, an open-label, randomized study to evaluate the
      efficacy of BRT compared with BR, was not conducted.
    

Eligibility criteria:

        Inclusion Criteria

          1. Age 18 years or older

          2. Histologically confirmed diagnosis of indolent non-Hodgkin's B-cell lymphoma (ie,
             follicular lymphoma, small lymphocytic lymphoma, and marginal zone lymphoma) that has
             relapsed (relapsed is defined as confirmed progressive disease (PD) after receiving
             the most recent prior therapy, or failure to achieve at least a partial response (PR)
             while receiving the most recent prior therapy)

          3. At least one prior line of therapy for indolent lymphoma

          4. Bi-dimensionally measurable disease with at least one lesion measuring >=1.5 cm in a
             single dimension

          5. Eastern Cooperative Oncology Group (ECOG) performance status of <= 2

          6. Creatinine clearance of >40 mL/min as calculated by the

        Cockcroft-Gault method as follows:

        (140 - age) * (weight in kg [* 0.85 if female] / 72 * serum creatinine level) 7. Adequate
        hepatic function, indicated as follows:

          -  aspartate aminotransferase (AST) of <2.5 x upper limit of normal (ULN)

          -  alanine aminotransferase (ALT) of <2.5 x ULN

          -  total bilirubin of <= 1.5 x ULN 8. Absolute neutrophil count (ANC) >=1000/mm3
             (1000/µL) 9. Platelet count >= 100,000/mm3 10. Female subjects of child-bearing
             potential and male subjects must use an acceptable form of birth control for the
             duration of their study participation and for 6 months after completing study drug
             dosing; acceptable forms of birth control, unless dictated otherwise by local
             regulatory authorities 11. For women of childbearing potential, a negative serum
             pregnancy test result obtained during the screening period and a negative urine
             pregnancy test result within 24 hours before first administration of study drug 12.
             Ability to understand the purpose and risks of the study and provide signed and dated
             informed consent and authorization to use protected health information

        Exclusion Criteria

          1. Diagnosis of grade 3b follicular lymphoma or transformed lymphoma of any grade

          2. Previously received TRU-016

          3. Prior treatment with rituximab if subject discontinued rituximab due to unresolved
             toxicity

          4. Refractory to bendamustine, defined as follows:

               -  progression within 6 months of last dose of bendamustine

               -  failed to achieve at least a PR while receiving bendamustine

               -  discontinued bendamustine due to toxicity

               -  received bendamustine within 6 months prior to first dose of study drug

          5. Received chemotherapy, radiotherapy, or immunotherapy including investigational agents
             within 28 days prior to the first dose of study drug

          6. Received therapeutic corticosteroids at doses equivalent to >10 mg prednisone per day
             for longer than 5 days within 14 days prior to the first dose of study drug, except if
             needed as a pre-medication

          7. Received filgrastim or equivalent within 14 days prior to screening (ie, collection of
             samples for laboratory tests) or pegfilgrastim within 28 days prior to screening (ie,
             collection of samples for laboratory tests)

          8. Prior allogeneic bone marrow transplant

          9. Prior autologous bone marrow transplant within 12 months prior to the first dose of
             study drug

         10. Received blood or platelet infusion within 7 days prior to screening (ie, collection
             of samples for laboratory tests)

         11. Previous or concurrent additional malignancy except non-invasive, non-melanomatous
             skin cancer or in situ carcinoma of the cervix, or other solid tumors if the subject
             has been disease-free for a minimum of 2 years prior to the first dose of study drug

         12. Known central nervous system or leptomeningeal lymphoma

         13. Any significant concurrent medical diseases or conditions, including but not limited
             to the following:

               -  Clinically significant pulmonary dysfunction requiring oxygen therapy

               -  An active infection (viral, bacterial, or fungal) requiring systemic therapy;
                  subjects receiving prophylactic therapy are eligible

         14. Known allergy to mannitol

         15. History of positive serology for human immunodeficiency virus (HIV)

         16. Positive serology for hepatitis B (surface antigen or core antibody) Note: If a
             positive test result for hepatitis B core antibody is due to immunoglobulin treatment,
             the subject may be enrolled if the hepatitis B viral deoxyribonucleic acid (DNA) is
             negative.

         17. Positive serology for hepatitis C

         18. Pregnant or breastfeeding

         19. Other severe, acute, or chronic medical or psychiatric condition, laboratory
             abnormality, or difficulty complying with protocol requirements that may increase the
             risk associated with study participation or study drug administration or may interfere
             with safety

         20. Any condition that, in the investigator's opinion, makes the subject unsuitable for
             study participation