Efficacy and Safety of the BiTE Antibody Blinatumomab in Chinese Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)
Condition: Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Blinatumomab; Dexamthasone
Intervention description: Blinatumomab will be supplied as single-use glass injection vials as a sterile, preservative-free, white to off-white, lyophilized powder for reconstitution and administration by continuous intravenous infusion (CIVI).
A single cycle of blinatumomab treatment is 6 weeks in duration, which includes 4 weeks of blinatumomab CIVI followed by a 2 week treatment-free interval. The treatment-free interval may be prolonged by up to 7 days, if deemed necessary by the investigator.; Premedication with dexamethasone was intended to prevent cytokine release syndrome (CRS) events associated with blinatumomab treatment. Treatment could start pre-study. Dexamethasone 20 mg IV was administered within 3 hours before start of blinatumomab in each treatment cycle, and within 3 hours before dose step increase.
Intervention MeSH terms: Blinatumomab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Evaluate the efficacy and safety of blinatumomab in Chinese 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
Masking: None (Open Label)
Enrollment: 121.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Relapsed; Refractory; B-precursor; Acute Lymphoblastic; Leukemia ALL; Blinatumomab; Chinese Adult Subjects

Summary:

      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
      leukemia (ALL).
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

          -  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

        Exclusion Criteria:

        Disease Related

          -  Subjects with Ph-positive ALL

          -  Subjects with Burkitt´s Leukemia according to World Health Organization (WHO)
             classification.

          -  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
             involvement

        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
             physician.

          -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of
             disease

          -  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
             treatment

          -  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

        General

          -  Known hypersensitivity to immunoglobulins or to any other component of the IMP
             formulation

          -  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
             disease)

          -  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.