Clinical Study With Blinatumomab in Pediatric and Adolescent Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

Relapsed/refractory B-precursor ALL in pediatric and adolescent patients is an aggressive
malignant disease with dismal prognosis. Apart from allogeneic hematological stem cell
transplantation (HSCT) there is not any other curative treatment of second relapse or
refractory B-precursor ALL available. Additional therapeutic approaches are urgently needed.
Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T
cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing
cells. The purpose of this study is to investigate the pharmacokinetics, pharmacodynamics
and safety of escalating doses of the BiTE® antibody blinatumomab (MT103)in pediatric and
adolescent patients with relapsed/refractory B-precursor ALL, to select a dose and to
investigate the efficacy and safety of that dose of blinatumomab in above mentioned patient
population. Patients will receive up to five 6-weeks cycles (4 weeks of continuous
intravenous infusion followed by a 2-weeks treatment free interval) of blinatumomab
treatment.

Inclusion Criteria:

- Morphologic evidence of B-precursor ALL with > 25% blasts in bone marrow (M3)at study
enrolment

- Age less than 18 years at enrollment

- Relapsed/refractory disease:

- Second or later bone marrow relapse,

- Any marrow relapse after allogeneic HSCT, or

- Refractory to other treatments: Patients in first relapse must have failed to
achieve a CR following full standard reinduction chemotherapy regimen of at
least 4 weeks duration.Patients who have not achieved a first remission must
have failed a full standard induction regimen

- Karnofsky performance status more than or equal to 50% for patients more than or
equal to 16 years and Lansky Performance Status (LPS) of more than or equal to 50%
for patients less than 16 years

- Organ function requirements: All patients must have adequate renal and liver
functions

Exclusion Criteria:

- Active acute or extensive chronic GvHD

- Immunosuppressive agents to prevent or treat GvHD within 2 weeks prior to
blinatumomab treatment

- Evidence for current CNS involvement by ALL (CNS 2, CNS 3) or testicular involvement
by ALL

- History of relevant CNS pathology or current relevant CNS pathology

- History of autoimmune disease with potential CNS involvement or current autoimmune
disease

- Any HSCT within 3 months prior to blinatumomab treatment

- Cancer chemotherapy within 2 weeks prior to blinatumomab treatment (except for
intrathecal chemotherapy and/or low dose maintenance therapy such as vinca alkaloids,
mercaptopurine, methotrexate, glucocorticoids)

- Chemotherapy related toxicities that haven't resolved to less than or equal to Grade
2

- Radiotherapy within 2 weeks prior to blinatumomab treatment

- Immunotherapy (e.g. rituximab, alemtuzumab) within 6 weeks prior to blinatumomab
treatment

- Any investigational product within 4 weeks prior to study entry

- Previous treatment with blinatumomab

- Active severe infection, any other concurrent disease or medical condition that could
be exacerbated by the treatment or would seriously complicate compliance with the
protocol

- Known infection with human immunodeficiency virus (HIV) or chronic infection with
hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive)