This study is being done to evaluate the rate of hematological response (complete
remission/complete remission with partial hematological recovery [CR/CRh*]) induced by
blinatumomab in Chinese adult subjects with relapsed/refractory B-precursor acute
lymphoblastic leukemia (ALL).
The study will consist of a screening period, a treatment period, and a follow-up period.
This is an open label, single-arm, multicenter phase 3 study to evaluate efficacy and safety
of the BiTE (bispecific T cell engager) antibody blinatumomab in Chinese adult subjects with
relapsed/refractory B-precursor ALL. The study will consist of a screening period, a
treatment period, and a follow-up period.
Treatment will consist of up to 5 cycles of blinatumomab. Subjects who have achieved a bone
marrow (BM) response (≤ 5% BM blasts) or CR/CRh*/CRi within 2 induction cycles of treatment
may continue to receive up to 3 additional consolidation cycles of blinatumomab. Thirty days
(± 3 days) after end of the last dose of protocol-specified therapy, subjects will have a
safety follow-up visit.
If subjects are suitable for alloHSCT after treatment with blinatumomab, they may undergo
alloHSCT instead of receiving further consolidation cycles with blinatumomab.
Subjects will be followed via clinic visit or telephone contact every 3 months +/- 2 weeks
after their safety follow-up visit until death has been observed or a maximum of 2 years
after start of treatment, whichever occurs first
101 Subjects have provided informed consent/assent prior to initiation of any
study-specific activities/procedures or subjects legally acceptable representative has
provided informed consent prior to any study-specific activities/procedures being initiated
when the subject has any kind of condition that, in the opinion of the investigator, may
compromise the ability of the subject to give written informed consent.
102 Subjects with Ph-negative B-precursor ALL, with any of the following:
- Primary refractory after induction therapy or who had relapsed within 12 months of
first remission or
- Relapsed within 12 months of receiving alloHSCT or
- Relapsed or refractory after first salvage therapy or beyond
103 > 5% blasts in BM (by morphology)
104 Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
105 Age ≥ 18 years at the time of informed consent
201 Subjects with Ph-positive ALL
202 Subjects with Burkitt´s Leukemia according to World Health Organization (WHO)
203 History or presence of clinically relevant CNS pathology as epilepsy, seizure, paresis,
aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease,
organic brain syndrome, and psychosis
204 Active ALL in the CNS (confirmed by cerebrospinal fluid [CSF] analysis) or testes
205 Isolated extramedullary disease
206 Current active autoimmune disease or history of autoimmune disease with potential CNS
Other Medical Conditions
207 History of malignancy other than ALL within 5 years prior to start of
protocol-specified therapy with the exception of:
- Malignancy treated with curative intent and with no known active disease present for 5
years before enrollment and felt to be at low risk for recurrence by the treating
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
- Adequately treated cervical carcinoma in situ without evidence of disease.
- Adequately treated breast ductal carcinoma in situ without evidence of disease.
- Prostatic intraepithelial neoplasia without evidence of prostate cancer.
208 Known infection with human immunodeficiency virus (HIV) or chronic infection with
hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive)
209 Abnormal screening laboratory values as defined below:
- Aspartate aminotransferase (AST) and/or alanine aminotransferase ALT and/or ALP ≥ 5 x
upper limit of normal (ULN)
- Total bilirubin (TBL) ≥ 1.5 x ULN (unless related to Gilbert´s or Meulengracht
- Creatinine ≥ 1.5 ULN or creatinine clearance < 60 ml/min (calculated)
Medications or Other Treatments
210 Autologous HSCT within 6 weeks prior to start of blinatumomab treatment
211 AlloHSCT within 3 months prior to start of blinatumomab treatment
212 Any active acute Graft-versus-Host Disease (GvHD), grade 2-4 according to the
Glucksberg criteria or active chronic GvHD requiring systemic treatment
213 Any systemic therapy against active GvHD within 2 weeks prior to start of blinatumomab
214 Cancer chemotherapy within 2 weeks prior to start of blinatumomab treatment
(intrathecal chemotherapy and dexamethasone are allowed until start of blinatumomab
treatment). In addition, any subject whose organ toxicity (excluding hematologic) from
prior ALL treatment has not resolved to common terminology criteria for adverse events
(CTCAE) ≤ grade 1.
215 Radiotherapy within 2 weeks prior to start of blinatumomab treatment
216 Immunotherapy (eg, rituximab) within 4 weeks prior to start of blinatumomab treatment
217 Currently receiving treatment in another investigational device or drug study, or less
than 4 weeks prior to start of blinatumomab treatment.
218 Previous treatment with anti-CD19 therapy
219 Known hypersensitivity to immunoglobulins or to any other component of the IMP
220 Pregnant women and women planning to become pregnant should not participate in this
study. Subjects who are breast feeding prior to start of blinatumomab treatment may be
enrolled if they stop breast feeding with breast milk produced during blinatumomab
treatment and for an additional 48 hours after the last dose of blinatumomab.
221 Woman of childbearing potential and is not willing to use 2 effective methods of
contraception during treatment and for an additional 48 hours after the last dose of
blinatumomab. Birth control is not required for postmenopausal women, or women with
uterus/or both ovaries/ or both fallopian tubes removed.
222 Male participants are not required to use birth control during treatment with
blinatumomab. However, you should let your female partner know you are in this study.
223 Subject likely to not be available to complete all protocol-required study visits or
procedures, including follow-up visits, and/or to comply with all required study procedures
to the best of the subject and investigator's knowledge.
224 History or evidence of any other clinically significant disorder, condition or disease
(with the exception of those outlined above) that, in the opinion of the Investigator or
Amgen physician, if consulted, would pose a risk to subject safety or interfere with the
study evaluation, procedures or completion.
225 Previous treatment with blinatumomab