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A Prospective Clinical Study of Bridging alloHSCT After Treatment With Obinutuzumab in Combination With Chidamide and Venetoclax in RR Ph-ALL and B-cell Lymphoma Patients

Primary Purpose

Acute Lymphoblastic Leukemia

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
chidamide
Venetoclax Oral Tablet
Inotuzumab Ozogamicin
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring acute lymphoblastic leukemia, chidamide

Eligibility Criteria

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

Inclusion Criteria: Confirmed diagnosis of acute lymphoblastic leukemia/lymphoblastic lymphoma with negative Ph chromosome or BCR/ABL fusion gene, and surface expression of CD22 on leukemic cells. First relapse, multiple relapses, or failure to achieve hematological remission after at least 3 cycles of intensive chemotherapy. Age greater than or equal to 18 years. Must have adequate organ function: Renal function and liver function as follows: AST, ALT, and ALP levels less than 2 times the upper limit of normal, total bilirubin level less than 1.5 times the upper limit of normal; Creatinine clearance greater than 50 mL/min; Pancreatic function: Serum amylase not higher than 1.5 times the upper limit of normal, serum lipase not higher than 1.5 times the upper limit of normal; Normal cardiac function: Ejection fraction (EF) > 60%, pulmonary artery systolic pressure ≤ 50 mmHg. HIV negative, HBV and HCV negative. Eastern Cooperative Oncology Group performance status assessment (ECOG-PS) score of 0-2. Informed consent must be signed before the start of the study. For participants aged 18 and above, the informed consent should be signed by the patient or their immediate family member. Considering the patient's condition, if it is not favorable for the patient to sign, the informed consent may be signed by a legal guardian or immediate family member of the patient. Exclusion Criteria: Lack of CD22 expression on the surface of leukemia cells. Mixed lineage leukemia. Patients with concomitant malignancies; patients assessed to have accompanying diseases that pose a severe risk to patient's life or would interfere with the completion of this study. Patients with a severe (≥ Grade 3) allergy to the components and excipients of obinutuzumab, idarubicin, and venetoclax. Clinically significant liver disease, such as a history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS); severe/uncontrolled liver disease, such as cirrhosis, decompensated liver disease, acute or chronic hepatitis. Active cardiac disease, defined as any of the following: history of any cardiac or vascular disease; uncontrolled or symptomatic history of angina pectoris; myocardial infarction within 6 months prior to study entry; history of clinically significant arrhythmia requiring medication or with severe clinical symptoms; uncontrolled or symptomatic congestive heart failure (> NYHA class 2); ejection fraction below the lower limit of normal range; pulmonary artery systolic pressure > 50 mmHg on echocardiography or clinical symptoms related to pulmonary arterial hypertension. Known positive serological reaction for HIV or active hepatitis C virus. Presence of psychiatric disorders or other conditions that would hinder compliance with study treatment and monitoring requirements. Inability or unwillingness to sign the informed consent form. Pregnant or lactating females. Patients deemed ineligible due to other specific circumstances as assessed by the investigator.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    combination drug group

    Arm Description

    Outcomes

    Primary Outcome Measures

    Overall survival
    One-year overall survival rate (OS) after allogeneic stem cell transplantation.

    Secondary Outcome Measures

    Complete remission
    Complete remission (CR) rate following treatment with obinutuzumab in combination with chidamide and venetoclax.
    relapse-free survival
    One-year relapse-free survival (RFS) after allogeneic stem cell transplantation.
    Incidence of graft-versus-host disease
    Incidence of graft-versus-host disease (GVHD) following allogeneic stem cell transplantation.
    Engraftment rate
    Engraftment rate post-transplantation.
    Minimal residual disease rate
    Minimal residual disease (MRD) clearance rate following chemotherapy.
    Bridging transplant rate.
    Bridging transplant rate.

    Full Information

    First Posted
    October 11, 2023
    Last Updated
    October 19, 2023
    Sponsor
    Institute of Hematology & Blood Diseases Hospital, China
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06087419
    Brief Title
    A Prospective Clinical Study of Bridging alloHSCT After Treatment With Obinutuzumab in Combination With Chidamide and Venetoclax in RR Ph-ALL and B-cell Lymphoma Patients
    Official Title
    A Prospective, Single-arm Clinical Study of Bridging Allogeneic Stem Cell Transplantation After Treatment With Obinutuzumab in Combination With Chidamide and Venetoclax in Relapsed/Refractory Ph-ALL and B-cell Lymphoma Patients
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 30, 2023 (Anticipated)
    Primary Completion Date
    December 30, 2024 (Anticipated)
    Study Completion Date
    December 30, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Institute of Hematology & Blood Diseases Hospital, China

    4. Oversight

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

    5. Study Description

    Brief Summary
    This study is a multicenter, prospective, interventional clinical trial aimed at recruiting relapsed/refractory Ph-ALL patients at multiple stem cell transplantation centers, including the Stem Cell Transplantation Center of the Chinese Academy of Medical Sciences Hematology Hospital. The anticipated enrollment is 42 subjects. The enrolled patients are planned to receive a treatment regimen of chidamide in combination with venetoclax and obinutuzumab. Patients who achieve remission will undergo allogeneic stem cell transplantation, followed by continued oral maintenance therapy with chidamide for one year post-transplantation based on the disease condition.
    Detailed Description
    Relapsed/refractory Ph-ALL patients who meet the inclusion criteria and provide informed consent will be enrolled in the study. They will receive combination chemotherapy with chidamide, venetoclax, and obinutuzumab. After one treatment cycle, if the patient achieves complete remission (CR) and minimal residual disease (MRD) negativity, they will proceed to the preparatory phase for allogeneic stem cell transplantation. In cases where MRD remains positive after one cycle of chemotherapy, the same regimen will be repeated for an additional cycle, followed by re-evaluation. Once MRD negativity is achieved, the patient will enter the preparatory phase for allogeneic stem cell transplantation. After successful hematopoietic recovery post-transplantation (neutrophil count >0.5×10^9/L, platelet count >50×10^9/L), chidamide 10mg qd will be added for maintenance therapy, which will be continued for one year post-transplantation.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Acute Lymphoblastic Leukemia
    Keywords
    acute lymphoblastic leukemia, chidamide

    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
    42 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    combination drug group
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    chidamide
    Intervention Description
    30mg twice weekly (BIW) for induction phase (cycle1-2,28 days per cycle)
    Intervention Type
    Drug
    Intervention Name(s)
    Venetoclax Oral Tablet
    Intervention Description
    400mg daily d1-14 induction phase (cycle1-2, 28 days per cycle)
    Intervention Type
    Drug
    Intervention Name(s)
    Inotuzumab Ozogamicin
    Intervention Description
    0.6 mg/m2 on day 1 of cycle 1-2(28 days per cycle)
    Primary Outcome Measure Information:
    Title
    Overall survival
    Description
    One-year overall survival rate (OS) after allogeneic stem cell transplantation.
    Time Frame
    24months
    Secondary Outcome Measure Information:
    Title
    Complete remission
    Description
    Complete remission (CR) rate following treatment with obinutuzumab in combination with chidamide and venetoclax.
    Time Frame
    24months
    Title
    relapse-free survival
    Description
    One-year relapse-free survival (RFS) after allogeneic stem cell transplantation.
    Time Frame
    24months
    Title
    Incidence of graft-versus-host disease
    Description
    Incidence of graft-versus-host disease (GVHD) following allogeneic stem cell transplantation.
    Time Frame
    24months
    Title
    Engraftment rate
    Description
    Engraftment rate post-transplantation.
    Time Frame
    24months
    Title
    Minimal residual disease rate
    Description
    Minimal residual disease (MRD) clearance rate following chemotherapy.
    Time Frame
    24months
    Title
    Bridging transplant rate.
    Description
    Bridging transplant rate.
    Time Frame
    24months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Confirmed diagnosis of acute lymphoblastic leukemia/lymphoblastic lymphoma with negative Ph chromosome or BCR/ABL fusion gene, and surface expression of CD22 on leukemic cells. First relapse, multiple relapses, or failure to achieve hematological remission after at least 3 cycles of intensive chemotherapy. Age greater than or equal to 18 years. Must have adequate organ function: Renal function and liver function as follows: AST, ALT, and ALP levels less than 2 times the upper limit of normal, total bilirubin level less than 1.5 times the upper limit of normal; Creatinine clearance greater than 50 mL/min; Pancreatic function: Serum amylase not higher than 1.5 times the upper limit of normal, serum lipase not higher than 1.5 times the upper limit of normal; Normal cardiac function: Ejection fraction (EF) > 60%, pulmonary artery systolic pressure ≤ 50 mmHg. HIV negative, HBV and HCV negative. Eastern Cooperative Oncology Group performance status assessment (ECOG-PS) score of 0-2. Informed consent must be signed before the start of the study. For participants aged 18 and above, the informed consent should be signed by the patient or their immediate family member. Considering the patient's condition, if it is not favorable for the patient to sign, the informed consent may be signed by a legal guardian or immediate family member of the patient. Exclusion Criteria: Lack of CD22 expression on the surface of leukemia cells. Mixed lineage leukemia. Patients with concomitant malignancies; patients assessed to have accompanying diseases that pose a severe risk to patient's life or would interfere with the completion of this study. Patients with a severe (≥ Grade 3) allergy to the components and excipients of obinutuzumab, idarubicin, and venetoclax. Clinically significant liver disease, such as a history of veno-occlusive disease (VOD) or sinusoidal obstruction syndrome (SOS); severe/uncontrolled liver disease, such as cirrhosis, decompensated liver disease, acute or chronic hepatitis. Active cardiac disease, defined as any of the following: history of any cardiac or vascular disease; uncontrolled or symptomatic history of angina pectoris; myocardial infarction within 6 months prior to study entry; history of clinically significant arrhythmia requiring medication or with severe clinical symptoms; uncontrolled or symptomatic congestive heart failure (> NYHA class 2); ejection fraction below the lower limit of normal range; pulmonary artery systolic pressure > 50 mmHg on echocardiography or clinical symptoms related to pulmonary arterial hypertension. Known positive serological reaction for HIV or active hepatitis C virus. Presence of psychiatric disorders or other conditions that would hinder compliance with study treatment and monitoring requirements. Inability or unwillingness to sign the informed consent form. Pregnant or lactating females. Patients deemed ineligible due to other specific circumstances as assessed by the investigator.

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

    Learn more about this trial

    A Prospective Clinical Study of Bridging alloHSCT After Treatment With Obinutuzumab in Combination With Chidamide and Venetoclax in RR Ph-ALL and B-cell Lymphoma Patients

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