Safety Study of the Bispecific T-cell Engager Blinatumomab (MT103) in Patients With Relapsed NHL
Condition: Non-Hodgkin's Lymphoma, Relapsed
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Blinatumomab (MT103)
Intervention description: Doses from 0.5 to 120 µg/m^2/24hours by continuous intravenous infusion
Intervention MeSH terms: Blinatumomab; Antibodies, Bispecific
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Hodgkin's Lymphoma; Cancer immunotherapy; Monoclonal antibody; anti-CD19; anti-CD3; BiTE; Blinatumomab

Summary:

      The purpose of this study is to determine whether a continuous infusion of Blinatumomab
      (MT103) is safe in the treatment of relapsed Non-Hodgkin's Lymphoma.

      Furthermore, the study is intended to provide pharmacokinetic and pharmacodynamic data of
      Blinatumomab as well as to get first indication of tumour activity.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with first or later relapse of histologically (World Health Organisation
             classification) confirmed:

               -  follicular lymphoma (grade I/II)

               -  marginal zone lymphoma

               -  lymphoplasmocytic lymphoma

               -  mantle cell lymphoma

               -  diffuse large B-cell lymphoma

               -  small lymphocytic lymphoma requiring therapy and not eligible for curative
                  treatment

          2. Measurable disease (at least one lesion >= 1.5 cm) documented by computed tomography
             (CT) scan

          3. Age >= 18 years

          4. Eastern Cooperative Oncology Group (ECOG) performance status <=2

          5. Life expectancy of at least 6 months

          6. Ability to understand the patient information and informed consent form

          7. Signed and dated written informed consent is available

          8. B:T cell ratio (Fluorescence-Activated Cell Sorter [FACS] analysis results by central
             lab) available before study entry.

        Exclusion Criteria:

          1. Any other NHL not listed in inclusion criterion 1

          2. Abnormal laboratory values as defined below:

               -  Peripheral lymphocyte count > 20 x 10^9/L

               -  Platelet counts ≤ 75,000/µL

               -  Hemoglobin level ≤ 9 g/dL

               -  Venous pH value out of normal range or oxygen saturation ≤ 90%

          3. Known or suspected central nervous system (CNS) involvement by NHL

          4. a)History of or current relevant CNS pathology as epilepsy, seizure, paresis,aphasia,
             apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome,
             psychosis b)Evidence for presence of inflammatory lesions and/or vasculitis on
             cerebral MRI

          5. Autologous stem cell transplantation within 12 weeks prior to study entry

          6. Allogeneic stem cell transplantation

          7. Cancer chemotherapy within 4 weeks prior to study entry

          8. Radiotherapy within 4 weeks prior to study entry

          9. Treatment with rituximab within 4 weeks prior to study entry

         10. Prior treatment with alemtuzumab 12 weeks prior to study entry

         11. Treatment with any investigational agent within 12 weeks prior to study entry

         12. Contraindication for any of the concomitant medications

         13. Abnormal renal or hepatic function as defined below:

               -  Aspartate aminotransferase (AST; SGOT) and/or alanine aminotransferase (ALT;
                  SGPT) >= 2 x upper limit of normal (ULN)

               -  total bilirubin >= 1.5 x ULN

               -  serum creatinine >= 2 x ULN

               -  creatinine clearance < 50mL/min

         14. Indication of hypercoagulative state as defined below:

             -antithrombin activity <LLN

         15. Presence of human anti-murine antibodies (HAMA) or known hypersensitivity to
             immunoglobulins

         16. History of malignancy other than B-cell lymphoma within 5 years prior to study entry,
             with the exception of basal cell carcinoma of the skin or carcinoma in situ of the
             cervix

         17. Active infection / not yet recovered from recent infection; known bacteriemia

         18. Any concurrent disease or medical condition that is deemed to interfere with the
             conduct of the study as judged by the investigator

         19. Regular dose of corticosteroids during the four weeks prior to D1 of this study or
             anticipated need of corticosteroids exceeding prednisone 20 mg/day or equivalent, or
             any other immunosuppressive therapy within 4 weeks prior to study entry

         20. Known infection with human immunodeficiency virus (HIV) or chronic infection with
             hepatitis B or hepatitis C virus

         21. Pregnant or nursing women, or women of childbearing potential not willing to use an
             effective form of contraception during participation in the study and at least three
             months thereafter. Male patients not willing to ensure that during the study and at
             least three months thereafter no fathering takes place.