Clinical Trials /

Efficacy and Safety of the BiTE Antibody Blinatumomab in Chinese Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)

NCT03476239

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Efficacy and Safety of the BiTE Antibody Blinatumomab in Chinese Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)
  • Official Title: An Open-label, Multicenter, Phase 3 Study to Evaluate Efficacy and Safety of the BiTE Antibody Blinatumomab in Chinese Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)

Clinical Trial IDs

  • ORG STUDY ID: 20130316
  • NCT ID: NCT03476239

Conditions

  • Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
BlinatumomabBLINCYTO®, AMG103, MT103blinatumomab

Purpose

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.

Detailed Description

      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
    

Trial Arms

NameTypeDescriptionInterventions
blinatumomabExperimentalApproximately 120 Chinese adult subjects
  • Blinatumomab

Eligibility Criteria

        Inclusion Criteria:

        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

        Exclusion Criteria:

        Disease Related

        201 Subjects with Ph-positive ALL

        202 Subjects with Burkitt´s Leukemia according to World Health Organization (WHO)
        classification.

        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
        involvement

        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
             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.

             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
             disease)

          -  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
        treatment

        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

        General

        219 Known hypersensitivity to immunoglobulins or to any other component of the IMP
        formulation

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in rate of hematological response [CR/CRh] induced by blinatumomab
Time Frame:Within 2 cycles of treatment (6 weeks/cycle)
Safety Issue:
Description:BM smears (slides) at screening and at the end of each treatment cycle (6 weeks/cycle) will be collected for cytomorphology testing. The degree of BM infiltration defined by the percentage of leukemic blasts in BM will be evaluated by local laboratories as per cytological assessment. In addition, the BM slides will be provided to the designated central laboratories for hematological assessment. The results of the local laboratory are applicable for inclusion into the study and for the decision if pre-treatment should be administered if the results of the central laboratory are not yet available at the time these decisions are made. For evaluation of baseline and response, the result of the central laboratory will prevail.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Trial Keywords

  • Relapsed
  • Refractory
  • B-precursor
  • Acute Lymphoblastic
  • Leukemia ALL
  • Blinatumomab
  • Chinese Adult Subjects

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