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

Study Overview
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Brief Summary
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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)

Official Title
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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)

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: MOR00208 (formerly Xmab5574)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MOR00208 (formerly Xmab5574)<br>intravenous Infusion of MOR00208, Fc-optimized Anti-CD19 Antibody | Drug: MOR00208 (formerly Xmab5574)<br> <br> * Other names: MOR208;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR= CR (Complete Remission) + PR (Partial Remission) Antitumor activity of MOR00208 | Throughout during study until progression, after each treatment cycle | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patients Response Duration Evaluation by Hematology, Bone Marrow Aspirates or Biopsy, CT | Two patients had a response to treatment. For one of the two patients a progression was recorded, the other patient was censored due to an AE. Conse quently, the planned Kaplan-Meier analyses of response duration and time to hematological relapse could not be calculated. | Throughout during study until progression, after each treatment cycle | 
| Safety Will be Evaluated by Assessing Adverse Events, Clinical Lab Data and Vital Signs, ECG, Physical Exam | Number of patients with at least one treatment-emergent AE | weekly, up to 7 months | 
| Pharmacokinetics of MOR00208 | Steady State Trough Plasma Concentration (Cpre-dose) at 9th dose (infusion) | weekly, up to 16 weeks, based on samples taken Pre-dose (ie before infusion start) | 
| Number of Patients Who Develop Ant-MOR00208 Antibodies as a Measure of Immunogenicity |  | monthly, up to 7 months | 
| Safety Will be Evaluated by Assessing Adverse Events, Clinical Lab Data and Vital Signs, ECG, Physical Exam | Number of patients with treatment-emergent AEs | weekly, up to 7 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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B-ALL, CD19, MOR208, MOR00208, Xmab5574, B-cell acute lymphoblastic leukemia, Fc-optimized Anti-CD19 Antibody