Study of Fc-Optimized Anti-CD19 Antibody (MOR00208) to Treat Non-Hodgkin's Lymphoma (NHL)
Condition: Non-Hodgkin Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: MOR00208 (formerly Xmab 5574)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 92.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NHL; CD19; MOR208; MOR00208; Xmab5574; B-Cell Non-Hodgkin´s Lymphoma; Fc-optimized Anti-CD19 Antibody; Tafasitamab

Summary:

      This is an open-label, multicenter study to characterize the safety and efficacy of the human
      anti-CD19 antibody MOR00208 in adult patients with relapsed/refractory non-Hodgkin's lymphoma
      (NHL) who have received at least 1 prior therapy containing rituximab (at least once).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patients ≥ 18 years of age.

          2. Histologically-confirmed diagnosis according to Revised European American
             Lymphoma/World Health Organization classification, of the following B-cell lymphomas:

               1. FL

               2. Other indolent NHL (eg, MZL/MALT)

               3. DLBCL

               4. MCL

          3. Patients' NHL must have progressed after at least 1 prior rituximab containing
             regimen.

          4. 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.

          5. 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.

          6. Discontinued previous monoclonal antibody therapy (except rituximab) or
             radioimmunotherapy administration for at least 60 days before study drug
             administration.

          7. 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.

          8. Patients with DLBCL had a positive [18F]fluorodeoxyglucose-positron emission
             tomography (FDG-PET) scan at baseline (Cheson 2007 response criteria).

          9. Life expectancy of > 3 months.

         10. Eastern Cooperative Oncology Group (ECOG) performance status of < 3.

         11. Laboratory criteria at screening:

               1. Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L

               2. Platelet count ≥ 75 × 10^9/L without previous transfusion within 10 days of first
                  study drug administration

               3. Haemoglobin ≥ 8.0 g/dL (may have been transfused)

               4. Serum creatinine < 2.0 x upper limit of normal (ULN)

               5. Total bilirubin ≤ 2.0 × ULN

               6. Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN

         12. 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.

         13. 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.

         14. Able to comply with all study-related procedures, medication use, and evaluations.

         15. Able to understand and give written informed consent and comply with the study
             protocol.

        Exclusion Criteria:

          1. 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.

          2. Treatment with a systemic investigational agent within 28 days before the screening
             visit.

          3. Previous treatment with an anti-CD19 antibody or fragments.

          4. Previous allogenic stem cell transplantation.

          5. Known or suspected hypersensitivity to the excipients contained in the study drug
             formulation.

          6. 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.

          7. 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.

          8. History of HIV infection.

          9. Any active systemic infection (viral, fungal, or bacterial) requiring active
             parenteral antibiotic therapy within 4 weeks of study drug administration.

         10. Current treatment with immunosuppressive agents other than prescribed corticosteroids
             (not more than 10-mg prednisone equivalent).

         11. Major surgery or radiation therapy within 4 weeks before first study drug
             administration.

         12. Systemic diseases (cardiovascular, renal, hepatic, etc) that would prevent study
             treatment in the investigator's opinion.

         13. History or clinical evidence of central nervous system (CNS), meningeal, or epidural
             disease, including brain metastasis.

         14. 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).

         15. Pregnancy or breastfeeding in women and women of childbearing potential not using an
             acceptable method of birth control.

         16. History of noncompliance to medical regimens or patients who are considered
             potentially unreliable not cooperative.