Study of Fc-Optimized Anti-CD19 Antibody (MOR00208) to Treat Non-Hodgkin's Lymphoma (NHL)

The study enrols patients from four different NHL subtypes: follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL) and other indolent NHL (iNHL). The study will employ a two-stage design where the decision to further enrol any NHL subtype in stage 2 will depend on best responses after two or three cycles in stage 1.

Inclusion criteria

• Male or female patients ≥ 18 years of age.
• Histologically-confirmed diagnosis according to Revised European American Lymphoma/World Health Organization classification, of the following B-cell lymphomas:

• FL
• Other indolent NHL (eg, MZL/MALT)
• DLBCL
• MCL
• Patients' NHL must have progressed after at least 1 prior rituximab containing regimen.
• One site of measurable disease by magnetic resonance imaging (MRI) or computed tomography (CT) scan defined as at least one lesion that measures at least 1.5 × 1.5 cm.

Exception:

For patients with MCL only, patients with nonmeasurable disease but evaluable sites (bone marrow, spleen, peripheral blood, gastrointestinal tract) can be enrolled.

• Patients who have previously received an autologous stem cell transplantation must be at least 4 weeks post-transplant before study drug administration and must have exhibited a full haematological recovery.
• Discontinued previous monoclonal antibody therapy (except rituximab) or radioimmunotherapy administration for at least 60 days before study drug administration.
• Off rituximab for at least 14 days before the screening visit and be confirmed to have either no response or have disease progression after rituximab treatment.
• Patients with DLBCL had a positive [18F]fluorodeoxyglucose-positron emission tomography (FDG-PET) scan at baseline (Cheson 2007 response criteria).
• Life expectancy of > 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of < 3.
• Laboratory criteria at screening:

• Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
• Platelet count ≥ 75 × 10^9/L without previous transfusion within 10 days of first study drug administration
• Haemoglobin ≥ 8.0 g/dL (may have been transfused)
• Serum creatinine < 2.0 x upper limit of normal (ULN)
• Total bilirubin ≤ 2.0 × ULN
• Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN
• If a female of childbearing potential, a negative pregnancy test must be confirmed before enrolment and use of double-barrier contraception or oral contraceptive plus barrier contraceptive must be used during the study and for 3 months after the last dose, or confirmation of having undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation.
• If a male, an effective barrier method of contraception must be used during the study and for 3 months after the last dose if the patient is sexually active with a female of childbearing potential.
• Able to comply with all study-related procedures, medication use, and evaluations.
• Able to understand and give written informed consent and comply with the study protocol.

Exclusion criteria

• Previous treatment with cytotoxic chemotherapy, immunotherapy, radiotherapy or other lymphoma specific therapy within 14 days before the screening visit or patient has not recovered from side effects of previous lymphoma-specific therapy.
• Treatment with a systemic investigational agent within 28 days before the screening visit.
• Previous treatment with an anti-CD19 antibody or fragments.
• Previous allogenic stem cell transplantation.
• Known or suspected hypersensitivity to the excipients contained in the study drug formulation.
• Clinically significant cardiovascular disease or cardiac insufficiency, cardiomyopathy, preexisting clinically significant arrhythmia, acute myocardial infarction within 3 months of enrolment, angina pectoris within 3 months of enrolment.
• Patients with positive hepatitis serology:

Hepatitis B (HBV): Patients with positive serology for HBV defined as positivity for hepatitis B surface antigen (HBsAg) or total anti-hepatitis B core antibody (anti-HBc). Patients positive for anti-HBc may be included if HBV DNA is not detectable.

Hepatitis C (HCV): Patients positive HCV serology (defined as positive for anti-HCV antibody [anti-HCV]) unless HCV-ribonucleic acid (RNA) is confirmed negative.

• History of HIV infection.
• Any active systemic infection (viral, fungal, or bacterial) requiring active parenteral antibiotic therapy within 4 weeks of study drug administration.
• Current treatment with immunosuppressive agents other than prescribed corticosteroids (not more than 10-mg prednisone equivalent).
• Major surgery or radiation therapy within 4 weeks before first study drug administration.
• Systemic diseases (cardiovascular, renal, hepatic, etc) that would prevent study treatment in the investigator's opinion.
• History or clinical evidence of central nervous system (CNS), meningeal, or epidural disease, including brain metastasis.
• Active treatment/chemotherapy for another primary malignancy within the past 5 years (except for ductal breast cancer in situ, non-melanoma skin cancer, prostate cancer not requiring treatment, and cervical carcinoma in situ).
• Pregnancy or breastfeeding in women and women of childbearing potential not using an acceptable method of birth control.
• History of noncompliance to medical regimens or patients who are considered potentially unreliable not cooperative.