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 adults with relapsed/refractory B-precursor acute lymphoblastic
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 adults 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. Participants who achieve 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
after end of the last dose of protocol-specified therapy, participants will have a safety
If subjects are suitable for allogeneic stem cell transplantation (alloHSCT) after treatment
with blinatumomab, they may undergo alloHSCT instead of receiving further consolidation
cycles with blinatumomab.
Participants will be followed via clinic visit or telephone contact every 3 months after
their safety follow-up visit until death has been observed or a maximum of 2 years after
start of treatment, whichever occurs first.
A planned interim analysis to assess efficacy and safety of blinatumomab was to be based on
the interim analysis set (N = 90). The efficacious benefit assessment based on an
O'Brien-Fleming alpha spending function (O'Brien and Fleming, 1979) with the critical
boundary 42.2% at the interim analysis and 39.2% at the primary analysis in CR/CRh* rate. If
the interim analysis showed statistically efficacious and overall benefit-risk analysis to be
promising per the data review team review, then the interim analysis could become the primary
analysis of this study. In addition, the study would continue its enrollment until 120
participants had been enrolled and continued their participation in the study to complete
The data cutoff date of 12 April 2019 allowed for the 90th participant enrolled before 21
February 2019 to have had the opportunity to complete 2 cycles of treatment and the safety
follow-up visit (if the participant had discontinued treatment after 2 cycles).
- 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
- 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 allogeneic hematopoietic stem cell
transplantation (alloHSCT) or
- Relapsed or refractory after first salvage therapy or beyond
- > 5% blasts in bone marrow (by morphology)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
- Age ≥ 18 years at the time of informed consent
- Subjects with Ph-positive ALL
- Subjects with Burkitt´s Leukemia according to World Health Organization (WHO)
- 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
- Active ALL in the central nervous system (CNS) (confirmed by cerebrospinal fluid [CSF]
analysis) or testes
- Isolated extramedullary disease
- Current active autoimmune disease or history of autoimmune disease with potential CNS
Other Medical Conditions
- 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.
- Known infection with human immunodeficiency virus (HIV) or chronic infection with
hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive)
Medications or Other Treatments
- Autologous HSCT within 6 weeks prior to start of blinatumomab treatment
- AlloHSCT within 3 months prior to start of blinatumomab treatment
- Any active acute Graft-versus-Host Disease (GvHD), grade 2-4 according to the
Glucksberg criteria or active chronic GvHD requiring systemic treatment
- Any systemic therapy against active GvHD within 2 weeks prior to start of blinatumomab
- 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.
- Radiotherapy within 2 weeks prior to start of blinatumomab treatment
- Immunotherapy (eg, rituximab) within 4 weeks prior to start of blinatumomab treatment
- Currently receiving treatment in another investigational device or drug study, or less
than 4 weeks prior to start of blinatumomab treatment.
- Previous treatment with anti-CD19 therapy
- Known hypersensitivity to immunoglobulins or to any other component of the IMP
- 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.
- 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.
- 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.
- 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.
- Previous treatment with blinatumomab
- Abnormal screening laboratory values as defined below:
- Aspartate aminotransferase (AST) and/or alanine aminotransferase ALT and/or alkaline
phosphatase (ALP) ≥ 5 * upper limit of normal (ULN)
- Total bilirubin (TBL) ≥ 1.5 * ULN (unless related to Gilbert´s or Meulengracht
- Creatinine ≥ 1.5 ULN or creatinine clearance < 60 ml/min (calculated)
- 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.