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

Related Clinical Trial
Vincristine, Dexamethasone, Doxorubicin, and PEG-asparaginase (VPLD) and Metformin for Relapsed Childhood Acute Lymphoblastic Leukemia (ALL) A Study Of Inotuzumab Ozogamicin Versus Investigator’s Choice Of Chemotherapy In Patients With Relapsed Or Refractory Acute Lymphoblastic Leukemia Effect of Vitamin D Diffiency on Oral Mucosa in Patients Recieving Methotrexate Chemotherapy Administration of Allogenic Red Blood Cells Loaded L-asparaginase in Cases of Relapse of Acute Lymphoblastic Leukaemia Pegylated Liposomal Doxorubicin Versus Daunorubicin to Treat Acute Lymphoblastic Leukemia: A Study of Children With Refractory or Relapsed ALL Therapy Protocol Acute Lymphoblastic Leukemia Stem Cell Transplantation International Pharmacogenetically Based Dosing of Thiopurines in Childhood Acute Lymphoblastic Leukemia ItaliaN Observational Study of Patients With Acute Lymphoblastic Leukemia Treated With Anti-CD22 Immunoconjugate Asparaginase Activity Monitoring (AAM) in Adult Patients With Acute Lymphoblastic Leukemia (ALL) Physical Activity to Modify Sequelae and Quality of Life in Childhood Acute Lymphoblastic Leukemia Alemtuzumab and Clofarabine for Relapsed or Refractory Acute Lymphoblastic Leukemia Phase II Front-line Ponatinib in Adult Philadelphia+/BCR-ABL+ Acute Lymphoblastic Leukemia. Total Therapy Study XVI for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia Total Therapy Study XIV for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia Clofarabine-cyclophosphamide as Salvage Therapy for Refractory and Relapsed Acute Lymphoblastic Leukemia (ALL) Adults Study Evaluating the Efficacy and Safety of JCAR015 in Adult B-cell Acute Lymphoblastic Leukemia (B-ALL) Induction Therapy With Cytarabine, High-Dose Mitoxantrone and Dasatinib for Patients With Philadelphia-Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia Tisagenlecleucel vs Blinatumomab or Inotuzumab for Patients With Relapsed/Refractory B-cell Precursor Acute Lymphoblastic Leukemia ALL2008 Protocol for Childhood Acute Lymphoblastic Leukemia Intermittent Versus Continuous PEG Asparaginase Bortezomib, Vorinostat and Dexamethasone for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) Liposomal Cytarabine for Central Nervous System (CNS)-Treatment in High-risk Acute Lymphoblastic Leukemia (ALL) Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL) Feasibility of Risk-Adapted Therapy in Young Adult Acute Lymphoblastic Leukemia: a Multicenter Trial Post-Frontline Sequential Treatment of Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia First-line Dasatinib Plus Conventional Chemotherapy in Adults With Newly Diagnosed Ph-Positive ALL CMC-544 in Relapsed Refractory Acute Lymphoblastic Leukemia (ALL) A Phase II, Open-Label Study of Clofarabine in Paediatric Patients With Refractory/Relapsed Acute Lymphoblastic Leukaemia A Study Of Two Inotuzumab Ozogamicin Doses in Relapsed/ Refractory Acute Lymphoblastic Leukemia Transplant Eligible Patients Rapamycin in Relapsed Acute Lymphoblastic Leukemia Treatment of Childhood Acute Lymphoblastic Leukemia Study Evaluating the Safety and Efficacy of Astarabine in Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia The Influence of Thiopurine Methyltransferase Activity on Toxicity After High-dose Methotrexate in Childhood Acute Lymphoblastic Leukemia CD19-CAR Immunotherapy for Childhood Acute Lymphoblastic Leukemia (ALL) Study of Imatinib-Combined Chemotherapy for BCR-ABL-Positive Acute Lymphoblastic Leukemia (ALL) Neurostimulation In Adult Survivors of Childhood Acute Lymphoblastic Leukemia (ALL) Precursor B Cell Acute Lymphoblastic Leukemia (B-ALL) Treated With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19 A Comparison of Reduced Dose Total Body Irradiation (TBI) and Cyclophosphamide With Fludarabine and Melphalan Reduced Intensity Conditioning in Adults With Acute Lymphoblastic Leukaemia (ALL) in Complete Remission. (ALL-RIC) Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase) in Elderly Patients With First Line Acute Lymphoblastic Leukemia Pharmacokinetic Profile of Vincristine Administered With Imatinib for Bcr-Abl Positive Acute Lymphoblastic Leukemia (ALL) Compared to That Without Imatinib for Bcr-Abl Negative ALL Phase III B in Acute Lymphoblastic Leukemia The Effects of Honey on Febrile Neutropenia in Children With Acute Lymphoblastic Leukemia Modified Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone) Program for Acute Lymphoblastic Leukemia Treatment of Acute Lymphoblastic Leukemia in Children PROCEDYTE: Depocyte® Administration (Liposomal Cytarabine) as Prophylaxis of Neuromeningeal Infiltration in Acute Lymphoblastic Leukemia A French Protocol for the Treatment of Acute Lymphoblastic Leukemia (ALL) in Children and Adolescents Treatment of High Risk Adult Acute Lymphoblastic Leukemia Efficacy and Safety of the BiTE Antibody Blinatumomab in Chinese Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Acute Lymphoblastic Leukemia (B-ALL) Medical Research Council (MRC) Working Party on Leukaemia in Children UK National Acute Lymphoblastic Leukaemia (ALL) Trial: UKALL 2003 A Study of Clofarabine in Japanese Paediatric Patients With Relapsed or Refractory Acute Lymphoblastic Leukaemia Rapamycin for Immunosuppression and B Cell Modulation Post Stem Cell Transplant for Acute Lymphoblastic Leukemia (ALL) The GD-2008 ALL Protocol for Childhood Acute Lymphoblastic Leukemia Cladribine in Combination With GAP in Patients With Refractory/Relapsed Acute Lymphoblastic Leukemia Liposomal Cytarabine in the Treatment of Central Nervous System Resistant or Relapsed Acute Lymphoblastic Leukemia in Children Clofarabine in Chinese Pediatric Patients With Refractory or Relapsed Acute Lymphoblastic Leukemia LAL-Ph-2000: Treatment of Acute Lymphoblastic Leukemia Chromosome Philadelphia Positive Total Therapy for Infants With Acute Lymphoblastic Leukemia (ALL) I Study of Sirolimus With PEG-Asparaginase in Acute Lymphoblastic Leukemia (ALL) Protocol For the Treatment Acute Lymphoblastic Leukemia With Ph ‘Negative in Elderly Patients (> 55 Years) Home-exercise Program for Children and Adolescent Survivors of Acute Lymphoblastic Leukemia The Association Between Asparaginase Enzyme Activity Levels and Toxicities in Childhood Acute Lymphoblastic Leukaemia in NOPHOALL 2008 A Study Evaluating KTE-X19 in Adult Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ZUMA-3) Retrospective Analysis of Survival in Adult MRD Positive Acute Lymphoblastic Leukemia Patients Liposomal Vincristine Plus Dexamethasone in Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia Treatment of Older Adults With Acute Lymphoblastic Leukemia Safety and Efficacy of Radio-immunotherapy (RIT) for Patients With Relapse or Refractory Acute Lymphoblastic Leukaemia (ALL) B CD22+ CTA101 UCAR-T Cell Injection for Treatment of Relapsed or Refractory CD19+ B-cell Acute Lymphoblastic Leukemia Pharmacogenetic Analysis of Korean Pediatric Patients With Acute Lymphoblastic Leukemia PETHEMA LAL-RI/96: Treatment for Patients With Standard Risk Acute Lymphoblastic Leukemia Rituximab Plus Chemotherapy for CD20+ Adult Acute Lymphoblastic Leukemia D-ALBA Frontline Sequential Dasatinib and Blinatumomab in Adult Philadelphia Positive Acute Lymphoblastic Leukemia Clinical Study With Blinatumomab in Pediatric and Adolescent Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia Comparative Efficacy and Safety of Two Asparaginase Preparations in Children With Previously Untreated Acute Lymphoblastic Leukaemia Clinical Study With Blinatumomab in Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) Osteonecrosis in Children With Acute Lymphoblastic Leukemia Safety and Efficacy of Entospletinib With Vincristine and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL) Pentoxifylline In Pediatric Acute Lymphoblastic Leukemia During Induction Bortezomib With Chemotherapy for Relapsed Pediatric Acute Lymphoblastic Leukemia (ALL) Study of Fc-Optimized Anti-CD19 Antibody (MOR00208) to Treat B-cell Acute Lymphoblastic Leukemia(B-ALL) STI 571 (GLIVEC) in the Treatment of Adult Acute Lymphoblastic Leukemia Effect of Omega-3 Fatty Acids on Methotrexate Induced Hepatotoxicity in Children With Acute Lymphoblastic Leukemia Treatment for Executive Dysfunction in Adult Survivors of Childhood Acute Lymphoblastic Leukemia LAL-AR-N-2005:Study Treatment for Children High Risk Acute Lymphoblastic Leukemia Study of Augmented Hyper-CVAD in Acute Lymphoblastic Leukemia Salvage Historical Data Analysis of Hematological Remission and Survival in Adults With R/R Acute Lymphoblastic Leukemia Inotuzumab Ozogamicin for Children With MRD Positive CD22+ Lymphoblastic Leukemia A Study in Adults With Untreated Acute Lymphoblastic Leukemia Acute Lymphoblastic Leukemia Relapse in Sweden 2003-2007 The Effects of Ankle Foot Orthoses on Gait Efficiency in Children With Acute Lymphoblastic Leukemia and Foot Drop Cancer Care Delivery in Adolescent and Young Adult Patients With Acute Lymphoblastic Leukemia Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia Haplo-identical HSCT Versus Chemotherapy for Adult Acute Lymphoblastic Leukemia Patients Metformin Reduce the Relapse Rate on Patients With B-cell Precursor (Ph+ Negative) Acute Lymphoblastic Leukemia Postural Control Under Different Cognitive Loads in Adult Survivors of Acute Lymphoblastic Leukemia and Age-Matched Healthy Individuals Genomic Changes in Childhood Acute Lymphoblastic Leukemia Role of the Microparticles and of Tissue Factor in the Pro-thrombotic Phenotype and the Thromboembolic Complications During the Acute Lymphoblastic Leukemia in Children. Allogeneic Stem Cell Transplantation (SCT) With Treosulfan, VP-16 and Cyclophosphamid for Patients With Acute Lymphoblastic Leukemia (ALL) Cardiometabolic Status in Childhood Acute Lymphoblastic Leukemia A Clinical Study of SHP674 in Patients With Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia Blinatumomab Maintenance Following Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Lymphoblastic Leukemia Pulses of Vincristine and Dexamethasone in BFM Protocols for Children With Acute Lymphoblastic Leukemia Neurologic Morbidity and Disability in Acute Lymphoblastic Leukemia Survivors Chimeric Antigen Receptor (CAR)-Modified T Cell Therapy in Treating Patients With Acute Lymphoblastic Leukemia New Markers for Minimal Residual Disease in Acute Lymphoblastic Leukemia Quality of Life Study for Adult Patients With Acute Lymphoblastic Leukemia Utility of XCL1 as a Prognostic Marker in Acute Lymphoblastic Leukemia FoxO3a and PU.1 in Acute Lymphoblastic Leukemia Clinical Significance of Occult Central Nervous System Disease In Adult Acute Lymphoblastic Leukemia Genome-wide Single Nucleotide Polymorphism (SNP) Array-based Approach to Predict Chemoresponse and Survival in Patients With Acute Lymphoblastic Leukemia Reduced Intensity Preparative Regimen Followed by Stem Cell Transplant (FAB)

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)

Brief 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 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 +/- 1 month
      after their safety follow-up visit until death has been observed or a maximum of 2 years
      after start of treatment, whichever occurs first
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Change in rate of hematological response [CR/CRh] induced by blinatumomab


Condition

Acute Lymphoblastic Leukemia

Intervention

Blinatumomab

Study Arms / Comparison Groups

 blinatumomab
Description:  Approximately 120 Chinese adult subjects

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

121

Start Date

October 18, 2017

Completion Date

April 25, 2021

Primary Completion Date

August 21, 2019

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)

        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.

        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

        226 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)

             227 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

MD, , 

Location Countries

China

Location Countries

China

Administrative Informations


NCT ID

NCT03476239

Organization ID

20130316


Responsible Party

Sponsor

Study Sponsor

Amgen


Study Sponsor

MD, Study Director, Amgen


Verification Date

October 2019