Study of Fc-Optimized Anti-CD19 Antibody (MOR00208) to Treat B-cell Acute Lymphoblastic Leukemia(B-ALL)

A Phase IIa, Single-arm, Open-label Study of MOR00208, a Humanized Fc-Engineered Anti-CD19 Antibody, in Patients With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia (B-ALL)

This is an open-label, multicentre study to characterize the safety and preliminary efficacy of the human anti CD19 antibody MOR00208 in adult subjects with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL)

Inclusion Criteria:

• Patients with previously treated Philadelphia-chromosome-negative B-ALL, with progression after at least one prior therapy. Patients with Philadelphia-chromosome-positive B-ALL can only be included if they are refractory or intolerant to at least one tyrosine-kinase-inhibitor.
• Male or female patients at least 16 years of age; if the patient is less than 18 years of age, the patient must have the ability to understand and give written assent in addition to the parent's/guardian's written informed consent.
• Patients with histologically confirmed diagnosis of B-ALL
• Mixed phenotype acute leukemia patients who have B cell immunophenotype.
• Patients with an Eastern Cooperative Oncology Group performance status of less than or equal to 2
• Patients with a total bilirubin of less than or equal to 2.0 mg/dL
• Patients with alanine aminotransferase or aspartate aminotransferase less than or equal to 2.5 times the upper limit of normal
• Patients with a creatinine level of less than or equal to 2.0 mg/dL
• If a female of childbearing potential, confirmation of a negative pregnancy test before enrollment and use of double-barrier contraception, confirmation of a negative pregnancy test before enrollment and use of oral contraceptive plus barrier contraceptive, or confirmation of having undergone clinically documented total hysterectomy, oophorectomy, or tubal ligation
• If a male, use of an effective barrier method of contraception during the study and for 3 months after the last dose if sexually active with a female of childbearing potential
• Patients with the ability to understand and give written informed consent and to comply with the study protocol

Exclusion Criteria:

• Patients who received previous treatment with an anti-CD19 antibody or fragments
• Receipt of anti-CD20 therapy no greater than 4 weeks before the first study dose
• Patients having undergone prior allogeneic stem cell transplantation within 3 months or having active graft versus host disease
• Patients with known hypersensitivity to any excipient contained in the drug formulation
• Patients with a New York Heart Association Class III or IV
• History of stroke or myocardial infarction within the last 6 months
• Patients with a history of positive human immunodeficiency virus test result (ELISA or western blot)
• Patients with positive hepatitis serology. Hepatitis B (HBV): Patients with positive serology for hepatitis B, defined as positive for hepatitis B surface antigen (HbsAg) or total anti-hepatitis B core antibody (anti-Hbc). Patients positive for anti- Hbc may be included if hepatitis B viral DNA is not detectable. Hepatitis C (HCV): Patients with positive hepatitis C serology (defined as positive for anti-hepatitis C virus antibody (anti-HCV) unless HCV-RNA is confirmed negative.
• Patients with active viral, bacterial, or systemic fungal infection requiring active parenteral treatment
• Patients who are receiving active treatment/chemotherapy for another primary malignancy or have received any treatment, including surgery, radiation, or chemotherapy, within the past 5 years (except ductal breast cancer in situ, for nonmelanoma skin cancer, prostate cancer not requiring treatment, and cervical carcinoma in situ)
• Patients who are pregnant or breastfeeding
• Patients with major surgery or radiation therapy within 4 weeks prior to first study dose