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Study to Evaluate Adverse Events and Movement of Intravenously (IV) Infused ABBV-787 in Adult Participants With Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)

Primary Purpose

Acute Myeloid Leukemia

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
ABBV-787
Sponsored by
AbbVie
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, AML, ABBV-787

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Laboratory Criteria matching those outlined in the protocol. QT interval corrected for heart rate (QTc) <= 470 msec using Fridericia's correction, and no other clinically significant cardiac abnormalities. Documented diagnosis of non-promyelocytic acute myeloid leukemia (AML), per 2022 European Leukemia Net (ELN) criteria. Participants with relapsed/refractory (R/R) acute myeloid leukemia (AML) who have been treated with up to 3 prior lines of therapy and are refractory to or intolerant of all established AML therapies that are known to clearly provide clinical benefit at the judgement of the investigator. Must have a white blood cell (WBC) count < 25 × 10^9 /L prior to initiation of study drug (Note: Hydroxyurea or leukapheresis is permitted to meet this criterion and for use through Cycle 3 to control for hyperleukocytosis.). Exclusion Criteria: Have received a CD33-targeting therapy within 3 months prior to the first dose of ABBV-787. Stem cell transplant within 3 months prior to first dose of study drug. Have received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 14 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-787. History of documented pneumonitis that required treatment with systemic steroids within the last 6 months, nor any evidence of active pneumonitis. Unresolved toxicity of Grade >= 2 from prior anticancer therapy, or to levels dictated in the eligibility criteria, with the exception of alopecia. Known active severe or poorly controlled acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    ABBV-787

    Arm Description

    Participants will receive increasing doses of ABBV-787 until the maximum tolerated dose (MTD) during the 3 year treatment period.

    Outcomes

    Primary Outcome Measures

    Number of Participants with Adverse Events (AE)
    An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
    Maximum Tolerated Dose (MTD) Based on Dose-Limiting Toxicities (DLT)
    DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.

    Secondary Outcome Measures

    Area Under the Plasma Concentration-time Curve (AUC) of ABBV-787
    AUC of ABBV-787.
    Maximum Observed Concentration (Cmax) of ABBV-787
    Cmax of ABBV-787.
    Time to Cmax (Tmax) of ABBV-787
    Tmax of ABBV-787.
    Half-life (t1/2) of ABBV-787
    t1/2 of ABBV-787.
    Total Antibody Concentration
    Total antibody concentration
    Plasma Concentrations of Unconjugated Bromodomain and Extra-terminal Domain (BET) Degrader Payload
    Plasma concentrations of unconjugated BET degrader payload.
    Antidrug Antibody (ADA)
    Incidence and concentration of anti-drug antibodies.
    Neutralizing Antibody (nAb)
    Incidence and concentration of neutralizing antibodies.
    Percentage of Participants Achieving Complete Remission (CR)
    CR is assessed by the European Leukemia Net (ELN). ELN defines refractory disease as the inability to attain complete remission (CR) or CR with incomplete hematologic recovery (CRi) after two courses of intensive induction treatment.
    Rate of Participants Achieving CR with partial hematologic recovery (CRh)
    Percentage of participants achieving CRh per ELN 2022.
    Rate of Participants Achieving CR with incomplete hematologic recovery (CRi)
    Percentage of participants achieving CRi per ELN 2022.
    Rate of Participants Achieving Composite CR (CR, CRh, or CRi)
    Composite CR is defined as the percentage of participants with composite CR per ELN 2022.
    Rate of Participants Achieving Partial Remission (PR)
    PR is defined as the percentage of participants with PR per ELN 2022.
    Duration of Response (DOR)
    DOR is defined for participants with CR, CRh, CRi, or PR as the time from the participant's initial response of CR, CRh, CRi, or PR per investigator review according to ELN 2022 criteria to disease progression or death of any cause, whichever occurs earlier.
    Number of Participants proceeding to hematopoietic stem cell transplant (HSCT)
    Number of participants proceeding to HSCT
    Event-free Survival (EFS)
    EFS is defined as the time from the date of the first study treatment to the date of treatment failure, or hematologic relapse from either CR, CRh, or CRi, or death from any cause, whichever occurs earlier.
    Relapse free survival (RFS)
    RFS is defined for participants achieving CR, CRh, or CRi as time from the date of achievement of remission (CR, CRh, or CRi) until the date of hematologic relapse or death from any cause.
    Overall survival (OS)
    OS is defined as time from first study treatment to death from any cause.

    Full Information

    First Posted
    September 29, 2023
    Last Updated
    September 29, 2023
    Sponsor
    AbbVie
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06068868
    Brief Title
    Study to Evaluate Adverse Events and Movement of Intravenously (IV) Infused ABBV-787 in Adult Participants With Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)
    Official Title
    A Phase 1 First-in-human Study Evaluating Safety, Pharmacokinetics, and Efficacy of ABBV-787 in Adult Subjects With Acute Myeloid Leukemia (AML)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 22, 2023 (Anticipated)
    Primary Completion Date
    December 12, 2029 (Anticipated)
    Study Completion Date
    December 12, 2029 (Anticipated)

    3. Sponsor/Collaborators

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

    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
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    Acute myeloid leukemia (AML) is the second most common type of leukemia diagnosed in adults and children, but most cases occur in adults. This study is to evaluate how safe ABBV-787 is and how it moves within the body in adult participants with relapsed/refractory (R/R) acute myeloid leukemia (AML). Adverse events and maximum tolerated dose (MTD) of ABBV-787 will be assessed. ABBV-787 is an investigational drug being developed for the treatment of AML. Participants will receive ABBV-787 in escalating doses until the maximum tolerated dose (MTD) is determined. Approximately 60 adult participants with a diagnosis of AML will be enrolled worldwide. Participants will receive intravenous (IV) infusions of ABBV-787 during the approximately 3 year duration a participant is followed. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests and checking for side effects.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Acute Myeloid Leukemia
    Keywords
    Acute Myeloid Leukemia, AML, ABBV-787

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    60 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    ABBV-787
    Arm Type
    Experimental
    Arm Description
    Participants will receive increasing doses of ABBV-787 until the maximum tolerated dose (MTD) during the 3 year treatment period.
    Intervention Type
    Drug
    Intervention Name(s)
    ABBV-787
    Intervention Description
    Intravenous (IV) Infusion
    Primary Outcome Measure Information:
    Title
    Number of Participants with Adverse Events (AE)
    Description
    An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
    Time Frame
    Up to Approximately 3 Years
    Title
    Maximum Tolerated Dose (MTD) Based on Dose-Limiting Toxicities (DLT)
    Description
    DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
    Time Frame
    Up to approximately 28 Days
    Secondary Outcome Measure Information:
    Title
    Area Under the Plasma Concentration-time Curve (AUC) of ABBV-787
    Description
    AUC of ABBV-787.
    Time Frame
    Up to Approximately 1 Year
    Title
    Maximum Observed Concentration (Cmax) of ABBV-787
    Description
    Cmax of ABBV-787.
    Time Frame
    Up to Approximately 1 Year
    Title
    Time to Cmax (Tmax) of ABBV-787
    Description
    Tmax of ABBV-787.
    Time Frame
    Up to Approximately 1 Year
    Title
    Half-life (t1/2) of ABBV-787
    Description
    t1/2 of ABBV-787.
    Time Frame
    Up to Approximately 1 Year
    Title
    Total Antibody Concentration
    Description
    Total antibody concentration
    Time Frame
    Up to Approximately 1 Year
    Title
    Plasma Concentrations of Unconjugated Bromodomain and Extra-terminal Domain (BET) Degrader Payload
    Description
    Plasma concentrations of unconjugated BET degrader payload.
    Time Frame
    Up to Approximately 1 Year
    Title
    Antidrug Antibody (ADA)
    Description
    Incidence and concentration of anti-drug antibodies.
    Time Frame
    Up to Approximately 1 Year
    Title
    Neutralizing Antibody (nAb)
    Description
    Incidence and concentration of neutralizing antibodies.
    Time Frame
    Up to Approximately 1 Year
    Title
    Percentage of Participants Achieving Complete Remission (CR)
    Description
    CR is assessed by the European Leukemia Net (ELN). ELN defines refractory disease as the inability to attain complete remission (CR) or CR with incomplete hematologic recovery (CRi) after two courses of intensive induction treatment.
    Time Frame
    Up to Approximately 1 Year
    Title
    Rate of Participants Achieving CR with partial hematologic recovery (CRh)
    Description
    Percentage of participants achieving CRh per ELN 2022.
    Time Frame
    Up to Approximately 1 Year
    Title
    Rate of Participants Achieving CR with incomplete hematologic recovery (CRi)
    Description
    Percentage of participants achieving CRi per ELN 2022.
    Time Frame
    Up to Approximately 1 Year
    Title
    Rate of Participants Achieving Composite CR (CR, CRh, or CRi)
    Description
    Composite CR is defined as the percentage of participants with composite CR per ELN 2022.
    Time Frame
    Up to Approximately 1 Year
    Title
    Rate of Participants Achieving Partial Remission (PR)
    Description
    PR is defined as the percentage of participants with PR per ELN 2022.
    Time Frame
    Up to Approximately 1 Year
    Title
    Duration of Response (DOR)
    Description
    DOR is defined for participants with CR, CRh, CRi, or PR as the time from the participant's initial response of CR, CRh, CRi, or PR per investigator review according to ELN 2022 criteria to disease progression or death of any cause, whichever occurs earlier.
    Time Frame
    Up to Approximately 1 Year
    Title
    Number of Participants proceeding to hematopoietic stem cell transplant (HSCT)
    Description
    Number of participants proceeding to HSCT
    Time Frame
    Up to Approximately 3 Years
    Title
    Event-free Survival (EFS)
    Description
    EFS is defined as the time from the date of the first study treatment to the date of treatment failure, or hematologic relapse from either CR, CRh, or CRi, or death from any cause, whichever occurs earlier.
    Time Frame
    Up to Approximately 3 Years
    Title
    Relapse free survival (RFS)
    Description
    RFS is defined for participants achieving CR, CRh, or CRi as time from the date of achievement of remission (CR, CRh, or CRi) until the date of hematologic relapse or death from any cause.
    Time Frame
    Up to Approximately 3 Years
    Title
    Overall survival (OS)
    Description
    OS is defined as time from first study treatment to death from any cause.
    Time Frame
    Up to Approximately 3 Years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Laboratory Criteria matching those outlined in the protocol. QT interval corrected for heart rate (QTc) <= 470 msec using Fridericia's correction, and no other clinically significant cardiac abnormalities. Documented diagnosis of non-promyelocytic acute myeloid leukemia (AML), per 2022 European Leukemia Net (ELN) criteria. Participants with relapsed/refractory (R/R) acute myeloid leukemia (AML) who have been treated with up to 3 prior lines of therapy and are refractory to or intolerant of all established AML therapies that are known to clearly provide clinical benefit at the judgement of the investigator. Must have a white blood cell (WBC) count < 25 × 10^9 /L prior to initiation of study drug (Note: Hydroxyurea or leukapheresis is permitted to meet this criterion and for use through Cycle 3 to control for hyperleukocytosis.). Exclusion Criteria: Have received a CD33-targeting therapy within 3 months prior to the first dose of ABBV-787. Stem cell transplant within 3 months prior to first dose of study drug. Have received anticancer therapy including chemotherapy, radiation therapy, immunotherapy, biologic, or any investigational therapy within 14 days or 5 half-lives of the drug (whichever is shorter) prior to the first dose of ABBV-787. History of documented pneumonitis that required treatment with systemic steroids within the last 6 months, nor any evidence of active pneumonitis. Unresolved toxicity of Grade >= 2 from prior anticancer therapy, or to levels dictated in the eligibility criteria, with the exception of alopecia. Known active severe or poorly controlled acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    ABBVIE CALL CENTER
    Phone
    844-663-3742
    Email
    abbvieclinicaltrials@abbvie.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    ABBVIE INC.
    Organizational Affiliation
    AbbVie
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Links:
    URL
    https://www.abbvieclinicaltrials.com/study/?id=M23-477
    Description
    Related Info

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    Study to Evaluate Adverse Events and Movement of Intravenously (IV) Infused ABBV-787 in Adult Participants With Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML)

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