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A Study of HY004 Treatment in Adult Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL) (B-ALL)

Primary Purpose

B-cell Acute Lymphoblastic Leukemia

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
HY004
Cyclophosphamide
Fludarabine Phosphate
Sponsored by
Juventas Cell Therapy Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for B-cell Acute Lymphoblastic Leukemia focused on measuring HY004, Cluster of differentiation antigen 19 and/or 22(CD19 and/or 22), CD19/22-directed CAR-T cells

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Signed written informed consent prior to any study procedures (patient and/or parent or legal guardian); Gender is not limited, and the age at the time of screening is ≥ 18 years old and ≤ 65 years old; Relapsed or refractory acute lymphoblastic leukemia (ALL); Documentation of CD19 and/orCD22 tumor expression demonstrated in bone marrow or peripheral blood within 3 months before screening; Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening; ECOG score 0-1 points; Organ function requirements: All patients must have adequate renal and liver functions. Exclusion Criteria: Active Central Nervous System (CNS) involvement by malignancy; Isolated extra-medullary disease relapse; Patients with Burkitt's lymphoma/leukemia; History of concomitant genetic syndrome; Patients with acute graft-versus-host disease (GVHD) or moderate-tosevere chronic GVHD within 4 weeks before screening; Patients with a history of allogeneic hematopoietic stem cell transplantation within 12 weeks before single collection; Active systemic autoimmune disease; Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti- HCV positive); Patients with active infections at screening; Patients who have used CAR-T cell therapy before screening; Patients with an expected lifespan of less than 3 months.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Participant Group

    Arm Description

    Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25-30 mg/m^2 intravenously [IV] over 30 minutes on Day -5, Day -4, and Day -3 and cyclophosphamide 500 mg/m^2 IV over 60 minutes on Day -5, Day -4), following a single IV infusion of chimeric antigen receptor (CAR) transduced autologous T cells(HY004).

    Outcomes

    Primary Outcome Measures

    Overall Remission Rate (ORR)
    ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification, as determined by Independent Review Committee (IRC).

    Secondary Outcome Measures

    Overall Remission Rate (ORR)
    ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification.
    Best overall response (BOR)
    The proportion of patients who have achieved the best response (CR or CRi) after HY004 treatment.
    Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity
    Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators; MRD negativity as determined using flow cytometry.
    Duration of remission (DOR)
    DOR is defined as the time between their first complete response per independent review to relapse or any death in the absence of documented relapse.
    Allogeneic Stem Cell Transplant (Allo-SCT) rate
    The proportion of patients who have received Allo-SCT after HY004 treatment.
    Relapse Free Survival (RFS)
    RFS is defined as the time from the HY004 infusion date to the date of disease relapse or death from any cause.
    Event-Free Survival(EFS)
    EFS is defined as the time from the HY004 infusion date to the date of any event, including disease progression, cessation of treatment for any reason, or death.
    Overall survival (OS)
    OS is defined as the time from the HY004 Cell Injection infusion to the date of death from any cause.
    Percentage of Participants Experiencing Treatment-Emergent Adverse Events（TEAE）
    Evaluate the type, frequency, severity of adverse events, and abnormal laboratory test values; Evaluate the frequency and severity of adverse events related to HY004.

    Full Information

    First Posted
    August 18, 2023
    Last Updated
    September 18, 2023
    Sponsor
    Juventas Cell Therapy Ltd.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06009107
    Brief Title
    A Study of HY004 Treatment in Adult Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)
    Acronym
    B-ALL
    Official Title
    A Phase I/II, Single Arm, Multi-center Study Evaluating the Safety and Efficacy of HY004 in Adult Patients With Relapsed/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
    October 18, 2023 (Anticipated)
    Primary Completion Date
    December 30, 2024 (Anticipated)
    Study Completion Date
    December 30, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Juventas Cell Therapy Ltd.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a multi-center, phase I/II trial to evaluate the safety and efficacy of HY004 treatment in Adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-cell ALL).
    Detailed Description
    This trial is a multi-center, open label, single-arm, phase I/II trial to evaluate the safety and efficacy of HY004 treatment in Adult (aged 18~65 years old) patients with r/r B-cell ALL. The phase I part of the trial is to evaluate the safety, optimal dose of HY004, Pharmacokinetics/Pharmacodynamics(PK/PD)and preliminary efficacy in the treatment of Adult patients with r/r B-cell ALL. The phase II part of the trial is to evaluate the efficacy and safety of HY004 in in the treatment of Adult patients with r/r B-cell ALL. The study includes screening, pre-treatment (Cell Product manufacture & lymphodepletion), HY004 infusion, safety and efficacy follow-up, and survival follow-up. All subjects who have received HY004 infusion will be followed for up to 2 years.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    B-cell Acute Lymphoblastic Leukemia
    Keywords
    HY004, Cluster of differentiation antigen 19 and/or 22(CD19 and/or 22), CD19/22-directed CAR-T cells

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1, Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    50 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Participant Group
    Arm Type
    Experimental
    Arm Description
    Participants with relapsed or refractory B-precursor acute lymphoblastic leukemia (r/r B-ALL) will receive conditioning chemotherapy (fludarabine 25-30 mg/m^2 intravenously [IV] over 30 minutes on Day -5, Day -4, and Day -3 and cyclophosphamide 500 mg/m^2 IV over 60 minutes on Day -5, Day -4), following a single IV infusion of chimeric antigen receptor (CAR) transduced autologous T cells(HY004).
    Intervention Type
    Biological
    Intervention Name(s)
    HY004
    Intervention Description
    A single infusion of Autologous 2nd generation CD19/CD22-directed CAR-T cells administered intravenously.
    Intervention Type
    Drug
    Intervention Name(s)
    Cyclophosphamide
    Intervention Description
    Administered intravenously.
    Intervention Type
    Drug
    Intervention Name(s)
    Fludarabine Phosphate
    Intervention Description
    Administered intravenously.
    Primary Outcome Measure Information:
    Title
    Overall Remission Rate (ORR)
    Description
    ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification, as determined by Independent Review Committee (IRC).
    Time Frame
    at the end of Month 3
    Secondary Outcome Measure Information:
    Title
    Overall Remission Rate (ORR)
    Description
    ORR is defined as Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi) per NCCN classification.
    Time Frame
    within 3 months
    Title
    Best overall response (BOR)
    Description
    The proportion of patients who have achieved the best response (CR or CRi) after HY004 treatment.
    Time Frame
    up to 2 years
    Title
    Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity
    Description
    Overall Remission Rate (ORR) with minimal residual disease (MRD) negativity as determined by IRC and Investigators; MRD negativity as determined using flow cytometry.
    Time Frame
    at the end of Month 3
    Title
    Duration of remission (DOR)
    Description
    DOR is defined as the time between their first complete response per independent review to relapse or any death in the absence of documented relapse.
    Time Frame
    to data cutoff date
    Title
    Allogeneic Stem Cell Transplant (Allo-SCT) rate
    Description
    The proportion of patients who have received Allo-SCT after HY004 treatment.
    Time Frame
    First infusion date of HY004 to data cutoff date(up to 2 years)
    Title
    Relapse Free Survival (RFS)
    Description
    RFS is defined as the time from the HY004 infusion date to the date of disease relapse or death from any cause.
    Time Frame
    up to 2 years
    Title
    Event-Free Survival(EFS)
    Description
    EFS is defined as the time from the HY004 infusion date to the date of any event, including disease progression, cessation of treatment for any reason, or death.
    Time Frame
    up to 2 years
    Title
    Overall survival (OS)
    Description
    OS is defined as the time from the HY004 Cell Injection infusion to the date of death from any cause.
    Time Frame
    2 years
    Title
    Percentage of Participants Experiencing Treatment-Emergent Adverse Events（TEAE）
    Description
    Evaluate the type, frequency, severity of adverse events, and abnormal laboratory test values; Evaluate the frequency and severity of adverse events related to HY004.
    Time Frame
    up to 2 years
    Other Pre-specified Outcome Measures:
    Title
    In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of transgene copy number per genomic DNA (gDNA) amount.
    Description
    To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of HY004 cells in target tissues (blood, bone marrow andCerebral Spinal Fluid (CSF)if available)by quantitative polymerase chain reaction(qPCR).
    Time Frame
    Up to 3 months(BM sample); Up to 2 years(Blood sample)
    Title
    In vivo cellular Pharmacokinetic (PK) profile of HY004 in units of percent of CAR-positive cells.
    Description
    To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of HY004 cells in target tissues (blood, bone marrow andCerebral Spinal Fluid (CSF)if available)by Flow Cytometry.
    Time Frame
    Up to 3 months(BM sample); Up to 2 years(Blood sample)
    Title
    In vivo cellular pharmacodynamics (PD) profile of HY004.
    Description
    To characterize the concentration of cytokines ,including Interleukin-6(IL-6) at least in Serum.
    Time Frame
    28 days
    Title
    Prevalence and incidence of humoral immunogenicity to HY004.
    Description
    To characterize the concentration of anti-drug antibodies.
    Time Frame
    2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Signed written informed consent prior to any study procedures (patient and/or parent or legal guardian); Gender is not limited, and the age at the time of screening is ≥ 18 years old and ≤ 65 years old; Relapsed or refractory acute lymphoblastic leukemia (ALL); Documentation of CD19 and/orCD22 tumor expression demonstrated in bone marrow or peripheral blood within 3 months before screening; Bone marrow with ≥ 5% lymphoblasts by morphologic assessment at screening; ECOG score 0-1 points; Organ function requirements: All patients must have adequate renal and liver functions. Exclusion Criteria: Active Central Nervous System (CNS) involvement by malignancy; Isolated extra-medullary disease relapse; Patients with Burkitt's lymphoma/leukemia; History of concomitant genetic syndrome; Patients with acute graft-versus-host disease (GVHD) or moderate-tosevere chronic GVHD within 4 weeks before screening; Patients with a history of allogeneic hematopoietic stem cell transplantation within 12 weeks before single collection; Active systemic autoimmune disease; Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti- HCV positive); Patients with active infections at screening; Patients who have used CAR-T cell therapy before screening; Patients with an expected lifespan of less than 3 months.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    JunYin Yu PM
    Phone
    +86-010-65960098
    Email
    yujunyin@juventas.cn
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jianxiang Wang M.D.
    Organizational Affiliation
    Study Principal Investigator Institute of Hematology & Blood Diseases Hospital
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    Currently the investigators have no plan of interim anaylsis, the investigators don't plan to share individual participant data(IPD) during the trial on-going.

    Learn more about this trial

    A Study of HY004 Treatment in Adult Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r B-ALL)

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