Clinical trial NCT01685021: Study of Fc-Optimized Anti-CD19 Antibody (MOR00208) to Treat B-cell Acute Lymphoblastic Leukemia(B-ALL)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Keywords: B-ALL
CD19
MOR208
MOR00208
Xmab5574
B-cell acute lymphoblastic leukemia
Fc-optimized Anti-CD19 Antibody
Lead sponsor: MorphoSys AG
Sponsor class: INDUSTRY
First posted: 2012-09-13
Enrollment: 22
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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)


Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Throughout during study until progression, after each treatment cycle
Secondary outcomes:
measure: Patients Response Duration Evaluation by Hematology, Bone Marrow Aspirates or Biopsy, CT
timeFrame: Throughout during study until progression, after each treatment cycle
measure: Safety Will be Evaluated by Assessing Adverse Events, Clinical Lab Data and Vital Signs, ECG, Physical Exam
timeFrame: weekly, up to 7 months
measure: Pharmacokinetics of MOR00208
timeFrame: weekly, up to 16 weeks, based on samples taken Pre-dose (ie before infusion start)
measure: Number of Patients Who Develop Ant-MOR00208 Antibodies as a Measure of Immunogenicity
timeFrame: monthly, up to 7 months
measure: Safety Will be Evaluated by Assessing Adverse Events, Clinical Lab Data and Vital Signs, ECG, Physical Exam
timeFrame: weekly, up to 7 months
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: MDA
name: Elias Jabbour, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University
name: Rebecca Klisovic, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Jude Children's Research Hospital
name: Wing H. Leung, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Klisovic RB, Leung WH, Brugger W, Dirnberger-Hertweck M, Winderlich M, Ambarkhane SV, Jabbour EJ. A phase 2a, single-arm, open-label study of tafasitamab, a humanized, Fc-modified, anti-CD19 antibody, in patients with relapsed/refractory B-precursor cell acute lymphoblastic leukemia. Cancer. 2021 Nov 15;127(22):4190-4197. doi: 10.1002/cncr.33796. Epub 2021 Aug 3.