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Study of Blinatumomab Administration in Chinese Pediatric Participants With Relapsed/Refractory B Precursor Acute Lymphoblastic Leukemia (R/R B-ALL)

Primary Purpose

B Precursor Acute Lymphoblastic Leukemia, Relapsed/Refractory B Precursor Acute Lymphoblastic Leukemia

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Blinatumomab
Sponsored by
Amgen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B Precursor Acute Lymphoblastic Leukemia focused on measuring Relapsed/Refractory B precursor Acute Lymphoblastic Leukemia, R/R B-ALL, Blinatumomab

Eligibility Criteria

1 Month - 204 Months (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participant's parent or legally authorized representative has provided informed consent when the participant is legally too young to provide informed consent and the participant has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated Pediatric participants aged > 1 month and < 18 years at the time of informed consent Relapsed or/refractory precursor B-cell acute lymphoblastic leukemia (ALL) disease, defined as ≥5% bone marrow blasts with at least one of the following: Second or later bone marrow relapse; Any marrow relapse after allogeneic hematopoietic stem cell transplant (alloHSCT); Refractory to other treatments: For participants in first relapse: failure to achieve a complete remission (CR) following a full standard reinduction chemotherapy regimen For participants who have not achieved a first remission, failure to achieve remission following a full standard induction regimen Karnofsky performance status ≥ 50% for participants ≥ 16 years Lansky performance status ≥ 50% for participants < 16 years Exclusion Criteria: - Evidence of current central nervous system (CNS) involvement by ALL. Participants with CNS disease at the time of relapse are eligible if CNS is successfully treated prior to enrollment. Other Medical Conditions Clinically relevant CNS pathology requiring treatment (eg, unstable epilepsy). Isolated extramedullary (EM) disease. Active malignancy other than ALL. Burkitt's leukemia according to the World Health Organization (WHO) 2016 criteria. Abnormal renal or hepatic function at screening as defined below: Abnormal serum creatinine based on age/gender as described by Threshold Creatinine Values Direct bilirubin > 1.5 mg/dl (25.6 μmol/L) at screening (unless related to Gilbert's or Meulengracht disease). Symptoms and/or clinical signs and/or radiological and/or sonographic signs that indicate an acute or uncontrolled chronic infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive) or hepatitis C virus (HCV) (anti-HCV positive). Known hypersensitivity to blinatumomab or any of the products or components of the blinatumomab formulation. Prior/Concomitant Therapy AlloHSCT within 12 weeks prior to start of protocol-specified therapy. Active acute or chronic Graft-versus-Host-Disease (GvHD) requiring systemic treatment with immunosuppressive medication. Radiotherapy within 2 weeks prior to start of protocol-specified therapy. Immunotherapy (eg, rituximab) within 4 weeks prior to start of protocol-specified therapy. Prior failed cluster of differentiation 19 (CD19) directed therapy such as prior blinatumomab or CD19 chimeric antigen receptor T cells (CAR T cell) will be allowed (with demonstrated continued CD19+ expression) if treatment ended > 4 weeks prior to start of protocol-specified therapy. Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy. With the exception of intrathecal chemotherapy and/or low dose maintenance therapy for example vinca alkaloids, mercaptopurine, methotrexate, or hydroxyurea or pre-phase chemotherapy and/or dexamethasone. Any low dose chemotherapy as stated above must be discontinued before starting pre-phase. Prior/Concurrent Clinical Study Experience - Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. Other Exclusions Female participants of childbearing potential with a positive pregnancy test assessed at Screening by a highly sensitive urine or serum pregnancy test. Female participants who are breastfeeding or who plan to breastfeed while on study through 12 months after the last dose of protocol-required treatment with highest teratogenic risk. Female participants of childbearing potential unwilling to use protocol-specified method of contraception during treatment and for an additional 12 months after the last dose of protocol-required treatment with highest teratogenic risk. Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 6 months after the last dose of protocol-required therapy with highest teratogenic risk. Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge. Female participants planning to become pregnant while on study through 12 months after the last dose of protocol-required treatment with highest teratogenic risk. Male participants unwilling to abstain from donating sperm during treatment and for an additional 6 months after the last dose of protocol-required treatment with highest teratogenic risk.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Blinatumomab

    Arm Description

    Participants will receive up to 5 cycles of blinatumomab (cycle is 42 days), including a 28-day continuous intravenous infusion (CIVI) of blinatumomab and a 14-day treatment free interval.

    Outcomes

    Primary Outcome Measures

    Number of Participants with Complete Remission (CR)
    Number of Participants with CR with Partial Recovery of Peripheral Blood Counts (CRh)

    Secondary Outcome Measures

    Number of Participants with Treatment-emergent Adverse Events (TEAEs)
    Number of Participants with Serious TEAEs
    Number of Participants with Treatment-related TEAEs
    Number of Participants with Adverse Events of Interest
    Steady State Concentration (Css) of Blinatumomab
    Clearance of Blinatumomab
    Overall Survival (OS) Rate
    Relapse-Free Survival (RFS) Rate
    Number of Participants who Receive Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT)
    100-day Mortality Rate After alloHSCT
    Number of Participants with Anti-blinatumomab Antibody (ADA) Formation
    Minimal Residual Disease (MRD) Response

    Full Information

    First Posted
    September 18, 2023
    Last Updated
    September 25, 2023
    Sponsor
    Amgen
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06054113
    Brief Title
    Study of Blinatumomab Administration in Chinese Pediatric Participants With Relapsed/Refractory B Precursor Acute Lymphoblastic Leukemia (R/R B-ALL)
    Official Title
    An Open-label, Multicenter, Phase 2 Study to Evaluate Efficacy, Safety, and Pharmacokinetics (PK) of Blinatumomab in Chinese Pediatric Subjects With Relapsed or Refractory B Precursor Acute Lymphoblastic Leukemia (R/R B-ALL)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 11, 2024 (Anticipated)
    Primary Completion Date
    October 22, 2025 (Anticipated)
    Study Completion Date
    March 10, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Amgen

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    Yes

    5. Study Description

    Brief Summary
    The primary objective of this study is to evaluate the efficacy of blinatumomab.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    B Precursor Acute Lymphoblastic Leukemia, Relapsed/Refractory B Precursor Acute Lymphoblastic Leukemia
    Keywords
    Relapsed/Refractory B precursor Acute Lymphoblastic Leukemia, R/R B-ALL, Blinatumomab

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    18 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Blinatumomab
    Arm Type
    Experimental
    Arm Description
    Participants will receive up to 5 cycles of blinatumomab (cycle is 42 days), including a 28-day continuous intravenous infusion (CIVI) of blinatumomab and a 14-day treatment free interval.
    Intervention Type
    Drug
    Intervention Name(s)
    Blinatumomab
    Other Intervention Name(s)
    Blincyto®
    Intervention Description
    Administered via CIVI
    Primary Outcome Measure Information:
    Title
    Number of Participants with Complete Remission (CR)
    Time Frame
    Up to 84 days
    Title
    Number of Participants with CR with Partial Recovery of Peripheral Blood Counts (CRh)
    Time Frame
    Up to 84 days
    Secondary Outcome Measure Information:
    Title
    Number of Participants with Treatment-emergent Adverse Events (TEAEs)
    Time Frame
    Up to approximately 240 days
    Title
    Number of Participants with Serious TEAEs
    Time Frame
    Up to approximately 2 years
    Title
    Number of Participants with Treatment-related TEAEs
    Time Frame
    Up to approximately 240 days
    Title
    Number of Participants with Adverse Events of Interest
    Time Frame
    Up to approximately 240 days
    Title
    Steady State Concentration (Css) of Blinatumomab
    Time Frame
    Days 3, 8, 9 and 29
    Title
    Clearance of Blinatumomab
    Time Frame
    Days 3, 8, 9 and 29
    Title
    Overall Survival (OS) Rate
    Time Frame
    Up to approximately 2 years
    Title
    Relapse-Free Survival (RFS) Rate
    Time Frame
    Up to approximately 2 years
    Title
    Number of Participants who Receive Allogeneic Hematopoietic Stem Cell Transplant (alloHSCT)
    Time Frame
    Up to approximately 2 years
    Title
    100-day Mortality Rate After alloHSCT
    Time Frame
    Up to approximately 2 years
    Title
    Number of Participants with Anti-blinatumomab Antibody (ADA) Formation
    Time Frame
    Up to approximately 240 days
    Title
    Minimal Residual Disease (MRD) Response
    Time Frame
    Up to 84 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    1 Month
    Maximum Age & Unit of Time
    204 Months
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Participant's parent or legally authorized representative has provided informed consent when the participant is legally too young to provide informed consent and the participant has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated Pediatric participants aged > 1 month and < 18 years at the time of informed consent Relapsed or/refractory precursor B-cell acute lymphoblastic leukemia (ALL) disease, defined as ≥5% bone marrow blasts with at least one of the following: Second or later bone marrow relapse; Any marrow relapse after allogeneic hematopoietic stem cell transplant (alloHSCT); Refractory to other treatments: For participants in first relapse: failure to achieve a complete remission (CR) following a full standard reinduction chemotherapy regimen For participants who have not achieved a first remission, failure to achieve remission following a full standard induction regimen Karnofsky performance status ≥ 50% for participants ≥ 16 years Lansky performance status ≥ 50% for participants < 16 years Exclusion Criteria: - Evidence of current central nervous system (CNS) involvement by ALL. Participants with CNS disease at the time of relapse are eligible if CNS is successfully treated prior to enrollment. Other Medical Conditions Clinically relevant CNS pathology requiring treatment (eg, unstable epilepsy). Isolated extramedullary (EM) disease. Active malignancy other than ALL. Burkitt's leukemia according to the World Health Organization (WHO) 2016 criteria. Abnormal renal or hepatic function at screening as defined below: Abnormal serum creatinine based on age/gender as described by Threshold Creatinine Values Direct bilirubin > 1.5 mg/dl (25.6 μmol/L) at screening (unless related to Gilbert's or Meulengracht disease). Symptoms and/or clinical signs and/or radiological and/or sonographic signs that indicate an acute or uncontrolled chronic infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (hepatitis B surface antigen [HBsAg] positive) or hepatitis C virus (HCV) (anti-HCV positive). Known hypersensitivity to blinatumomab or any of the products or components of the blinatumomab formulation. Prior/Concomitant Therapy AlloHSCT within 12 weeks prior to start of protocol-specified therapy. Active acute or chronic Graft-versus-Host-Disease (GvHD) requiring systemic treatment with immunosuppressive medication. Radiotherapy within 2 weeks prior to start of protocol-specified therapy. Immunotherapy (eg, rituximab) within 4 weeks prior to start of protocol-specified therapy. Prior failed cluster of differentiation 19 (CD19) directed therapy such as prior blinatumomab or CD19 chimeric antigen receptor T cells (CAR T cell) will be allowed (with demonstrated continued CD19+ expression) if treatment ended > 4 weeks prior to start of protocol-specified therapy. Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy. With the exception of intrathecal chemotherapy and/or low dose maintenance therapy for example vinca alkaloids, mercaptopurine, methotrexate, or hydroxyurea or pre-phase chemotherapy and/or dexamethasone. Any low dose chemotherapy as stated above must be discontinued before starting pre-phase. Prior/Concurrent Clinical Study Experience - Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded. Other Exclusions Female participants of childbearing potential with a positive pregnancy test assessed at Screening by a highly sensitive urine or serum pregnancy test. Female participants who are breastfeeding or who plan to breastfeed while on study through 12 months after the last dose of protocol-required treatment with highest teratogenic risk. Female participants of childbearing potential unwilling to use protocol-specified method of contraception during treatment and for an additional 12 months after the last dose of protocol-required treatment with highest teratogenic risk. Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 6 months after the last dose of protocol-required therapy with highest teratogenic risk. Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge. Female participants planning to become pregnant while on study through 12 months after the last dose of protocol-required treatment with highest teratogenic risk. Male participants unwilling to abstain from donating sperm during treatment and for an additional 6 months after the last dose of protocol-required treatment with highest teratogenic risk.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Amgen Call Center
    Phone
    866-572-6436
    Email
    medinfo@amgen.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    MD
    Organizational Affiliation
    Amgen
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
    IPD Sharing Time Frame
    Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
    IPD Sharing Access Criteria
    Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
    IPD Sharing URL
    https://www.amgen.com/datasharing
    Links:
    URL
    http://www.amgentrials.com
    Description
    AmgenTrials clinical trials website

    Learn more about this trial

    Study of Blinatumomab Administration in Chinese Pediatric Participants With Relapsed/Refractory B Precursor Acute Lymphoblastic Leukemia (R/R B-ALL)

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