Safety Study of the Bispecific T-cell Engager Blinatumomab (MT103) in Patients With Relapsed NHL

Inclusion Criteria

• 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
• Measurable disease (at least one lesion >= 1.5 cm) documented by computed tomography (CT) scan
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 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%
• Known or suspected central nervous system (CNS) involvement by NHL
• 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
• Autologous stem cell transplantation within 12 weeks prior to study entry
• Allogeneic stem cell transplantation
• Cancer chemotherapy within 4 weeks prior to study entry
• Radiotherapy within 4 weeks prior to study entry
• Treatment with rituximab within 4 weeks prior to study entry
• Prior treatment with alemtuzumab 12 weeks prior to study entry
• Treatment with any investigational agent within 12 weeks prior to study entry
• Contraindication for any of the concomitant medications
• 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
• Indication of hypercoagulative state as defined below:

-antithrombin activity <LLN

• Presence of human anti-murine antibodies (HAMA) or known hypersensitivity to immunoglobulins
• 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
• Active infection / not yet recovered from recent infection; known bacteriemia
• Any concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator
• 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
• Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B or hepatitis C virus
• 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.