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Study of Efficacy of BZ019 in Large B-cell Lymphoma

Primary Purpose

Large B-cell Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
BZ019
Sponsored by
Shanghai Mengchao Cancer Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Large B-cell Lymphoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 1)Written informed consent must be obtained prior to any screening procedures;
  • 2)75 ≥Age ≥ 18 years subjects;
  • 3)Subjects who meet the following diagnostic and therapeutic requirements when screening: A)The diagnosis of B Cell NHL was consistent with WHO classification in 2017;

B) Subjects must be accepted adequate treatment before and have received at least 2 lines of treatment or relapse or progress after autologous hematopoietic stem cell transplantation, and the treatment history at least include:

a)Treatment by CD20 monoclonal antibody (Rituximab) except for CD20 negative; b) A chemotherapy regimen containing anthracyclines.

C)With Relapsed or refractory large B-cell lymphoma when screening:

a) The definition of relapsing is as follows:PD occurs at least after remission (including PR or CR) with standard therapy (including Rituximab) b) The definition of refractory is as follows: i) No response to the last treatment, including:The best response to the latest treatment is PD or SD; ii)Disease progression after ASCT or recurrence within ≤ 12 months (recurrence must be confirmed by biopsy), or if receiving remedial treatment after ASCT, the subject must have no reaction or recurrence after the last treatment.

D) CD19+ which was detected by immunocytochemistry or flow cytometric ;

  • 4)According to the preliminary evaluation, staging and response evaluation recommendations for Hodgkin and non Hodgkin's lymphoma (2014 Edition), at least one measurable lesion was found in the screening period:the length diameter of the intranodal lesion was greater than 1.5cm,the diameter of the external lesion was greater than 1.0cm;
  • 5) Life expectancy ≥12 weeks;
  • 6)Baseline Eastern Cooperative Oncology Group (ECOG) score is 0 or 2 Baseline Eastern Cooperative Oncology Group (ECOG) score is 0 or 2 ;
  • 7)Adequate organ function:

A)Renal function defined as:

a)A serum creatinine of ≤1.5 x ULN or Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73 m^2;

B)Liver function defined as:

b) Alanine Aminotransferase (ALT) ≤ 5 x ULN;Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert-Meulengracht syndrome; patients with Gilbert-Meulengracht syndrome may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN; c) Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 91% on room air;

  • 8)Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) ≥ 50%, confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA);
  • 9)No blood transfusion within 1 week before signing the informed consent, sufficient bone marrow reserve is available, which is defined as: A)Absolute neutrophil count (ANC) >1x10^9/L; B)Absolute lymphocyte count (ALC) ≥ 0.5x10^9/L; C)Platelets ≥ 50x10^9/L; D)Hemoglobin > 80 g/L, for patients with bone marrow invasion, hemoglobin > 60g/L can be considered into the group;
  • 10)Must have an apheresis product of non-mobilized cells accepted for manufacturing;
  • 11)If the patient uses the following drugs, the following conditions should be met: A)glucocorticoids: The treatment dose of glucocorticoids must be stopped 72 hours before BZ019 infusion. However, glucocorticoids of physiological alternative dose are allowed: prednisone or its equivalent ≤ 15 mg / day; B)Immunosuppression: Any immunosuppressive medication must be stopped ≥ 4 weeks prior to enrollment; C) Antiproliferative therapies other than lymphodepleting chemotherapy within two weeks of infusion; D) Antibody use including anti-CD20 therapy within 4 weeks prior to infusion or 5 half-lives of the respected antibody, whichever is longer; E)CNS disease prophylaxis must be stopped > 1 week prior to BZ019 infusion (e.g. intrathecal methotrexate);
  • 12)Women of child-bearing age and all male subjects must agree to use effective contraceptive methods until BZ019 are no longer present in the body (detected by PCR).

Exclusion Criteria:

  • • Patients who have previously received any anti-CD45, anti-CD19 or anti-CD3 therapy;

    • Patients who have previously received any adoptive T cell therapy or gene therapy products, including CAR-T therapy;
    • Active Central Nervous System (CNS) involvement by malignancy or secondary CNS involvement
    • History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or self-immune disease with CNS involvement.
    • Prior allogeneic HSCT.
    • Patients with positive hepatitis B (HBsAg and / or HBcAb positive, except for those with positive surface antibody alone) or hepatitis C serological markers;
    • HIV positive or Treponema pallidum positive patients.
    • Patients with uncontrollable active or life-threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours before infusion);
    • Patients with unstable angina and / or myocardial infarction within 6 months before screening, or patients with serious or uncontrollable other diseases (such as unstable or uncompensated respiratory, heart, liver or kidney diseases) during screening;

Previous or concurrent malignancy with the following exceptions:

  1. Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)
  2. In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study
  3. A primary malignancy which has been completely resected and in complete remission for ≥ 5 years

    • Pregnant or nursing (lactating) women.
    • Patients with uncontrolled arrhythmia.
    • Patients on oral anticoagulation therapy within 1 week prior to BZ019 infusion.
    • Patients with active neurological auto immune or inflammatory disorders(e.g. Guillain Barre Syndrome, Amyptrophic Lateral Sclerosis)
    • Other conditions, such as compliance, that the investigators consider should not be included in this clinical trial.

Sites / Locations

  • Shanghai Mengchao Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BZ019

Arm Description

The subjects are enrolled into single-dose(1~5x10^6/kg) of BZ019 ( non viral vector CD19-targeted Chimeric Antigen Receptor (CAR) T Cells Injection).

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
Clinical response will be assessed by RECIST 1.1.

Secondary Outcome Measures

Pharmacokinetics (PK)
Peak Plasma Concentration (Cmax)
Pharmacodynamics (PD)
PD of IL-2, IL-4, IL-6,IL-10, IL-15, IFN-γ, TNF-α will be analysed after CAR T cell infusion
Quality of life(QOL)
Quality of life will be assessed by EQ-5D health Index scale

Full Information

First Posted
July 21, 2022
Last Updated
July 21, 2022
Sponsor
Shanghai Mengchao Cancer Hospital
Collaborators
Shanghai Cell Therapy Group Co.,Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05472610
Brief Title
Study of Efficacy of BZ019 in Large B-cell Lymphoma
Official Title
A Phase II Clinical Study of CD19-targeted Chimeric Antigen Receptor (CAR) T Cells Injection, for Relapsed and Refractory (R/R) Large B-cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 4, 2021 (Actual)
Primary Completion Date
January 2023 (Anticipated)
Study Completion Date
January 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Mengchao Cancer Hospital
Collaborators
Shanghai Cell Therapy Group Co.,Ltd

4. Oversight

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

5. Study Description

Brief Summary
This is a single arm,open-label, non-randomized phase 2 study to determine the efficacy of BZ019 in relapsed or refractory CD19+ B-cell Lymphoma subjects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Large B-cell Lymphoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
BZ019
Arm Type
Experimental
Arm Description
The subjects are enrolled into single-dose(1~5x10^6/kg) of BZ019 ( non viral vector CD19-targeted Chimeric Antigen Receptor (CAR) T Cells Injection).
Intervention Type
Biological
Intervention Name(s)
BZ019
Intervention Description
A treatment program will include lymphodepleting chemotherapy with fludarabine and cyclophosphamide (flu/cy) followed by single-dose of BZ019 administered intravenously (IV).
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
Clinical response will be assessed by RECIST 1.1.
Time Frame
Month 3
Secondary Outcome Measure Information:
Title
Pharmacokinetics (PK)
Description
Peak Plasma Concentration (Cmax)
Time Frame
Month 12
Title
Pharmacodynamics (PD)
Description
PD of IL-2, IL-4, IL-6,IL-10, IL-15, IFN-γ, TNF-α will be analysed after CAR T cell infusion
Time Frame
Month 12
Title
Quality of life(QOL)
Description
Quality of life will be assessed by EQ-5D health Index scale
Time Frame
Month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1)Written informed consent must be obtained prior to any screening procedures; 2)75 ≥Age ≥ 18 years subjects; 3)Subjects who meet the following diagnostic and therapeutic requirements when screening: A)The diagnosis of B Cell NHL was consistent with WHO classification in 2017; B) Subjects must be accepted adequate treatment before and have received at least 2 lines of treatment or relapse or progress after autologous hematopoietic stem cell transplantation, and the treatment history at least include: a)Treatment by CD20 monoclonal antibody (Rituximab) except for CD20 negative; b) A chemotherapy regimen containing anthracyclines. C)With Relapsed or refractory large B-cell lymphoma when screening: a) The definition of relapsing is as follows:PD occurs at least after remission (including PR or CR) with standard therapy (including Rituximab) b) The definition of refractory is as follows: i) No response to the last treatment, including:The best response to the latest treatment is PD or SD; ii)Disease progression after ASCT or recurrence within ≤ 12 months (recurrence must be confirmed by biopsy), or if receiving remedial treatment after ASCT, the subject must have no reaction or recurrence after the last treatment. D) CD19+ which was detected by immunocytochemistry or flow cytometric ; 4)According to the preliminary evaluation, staging and response evaluation recommendations for Hodgkin and non Hodgkin's lymphoma (2014 Edition), at least one measurable lesion was found in the screening period:the length diameter of the intranodal lesion was greater than 1.5cm,the diameter of the external lesion was greater than 1.0cm; 5) Life expectancy ≥12 weeks; 6)Baseline Eastern Cooperative Oncology Group (ECOG) score is 0 or 2 Baseline Eastern Cooperative Oncology Group (ECOG) score is 0 or 2 ; 7)Adequate organ function: A)Renal function defined as: a)A serum creatinine of ≤1.5 x ULN or Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73 m^2; B)Liver function defined as: b) Alanine Aminotransferase (ALT) ≤ 5 x ULN;Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert-Meulengracht syndrome; patients with Gilbert-Meulengracht syndrome may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN; c) Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 91% on room air; 8)Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) ≥ 50%, confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA); 9)No blood transfusion within 1 week before signing the informed consent, sufficient bone marrow reserve is available, which is defined as: A)Absolute neutrophil count (ANC) >1x10^9/L; B)Absolute lymphocyte count (ALC) ≥ 0.5x10^9/L; C)Platelets ≥ 50x10^9/L; D)Hemoglobin > 80 g/L, for patients with bone marrow invasion, hemoglobin > 60g/L can be considered into the group; 10)Must have an apheresis product of non-mobilized cells accepted for manufacturing; 11)If the patient uses the following drugs, the following conditions should be met: A)glucocorticoids: The treatment dose of glucocorticoids must be stopped 72 hours before BZ019 infusion. However, glucocorticoids of physiological alternative dose are allowed: prednisone or its equivalent ≤ 15 mg / day; B)Immunosuppression: Any immunosuppressive medication must be stopped ≥ 4 weeks prior to enrollment; C) Antiproliferative therapies other than lymphodepleting chemotherapy within two weeks of infusion; D) Antibody use including anti-CD20 therapy within 4 weeks prior to infusion or 5 half-lives of the respected antibody, whichever is longer; E)CNS disease prophylaxis must be stopped > 1 week prior to BZ019 infusion (e.g. intrathecal methotrexate); 12)Women of child-bearing age and all male subjects must agree to use effective contraceptive methods until BZ019 are no longer present in the body (detected by PCR). Exclusion Criteria: • Patients who have previously received any anti-CD45, anti-CD19 or anti-CD3 therapy; Patients who have previously received any adoptive T cell therapy or gene therapy products, including CAR-T therapy; Active Central Nervous System (CNS) involvement by malignancy or secondary CNS involvement History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or self-immune disease with CNS involvement. Prior allogeneic HSCT. Patients with positive hepatitis B (HBsAg and / or HBcAb positive, except for those with positive surface antibody alone) or hepatitis C serological markers; HIV positive or Treponema pallidum positive patients. Patients with uncontrollable active or life-threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours before infusion); Patients with unstable angina and / or myocardial infarction within 6 months before screening, or patients with serious or uncontrollable other diseases (such as unstable or uncompensated respiratory, heart, liver or kidney diseases) during screening; Previous or concurrent malignancy with the following exceptions: Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry) In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study A primary malignancy which has been completely resected and in complete remission for ≥ 5 years Pregnant or nursing (lactating) women. Patients with uncontrolled arrhythmia. Patients on oral anticoagulation therapy within 1 week prior to BZ019 infusion. Patients with active neurological auto immune or inflammatory disorders(e.g. Guillain Barre Syndrome, Amyptrophic Lateral Sclerosis) Other conditions, such as compliance, that the investigators consider should not be included in this clinical trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhang Yan, Ph. D
Phone
021-67091122
Email
1r1-7v5o4ef29a@dingtalk.com
First Name & Middle Initial & Last Name or Official Title & Degree
Liang Lijuan, Bachelor
Phone
021-67091022
Email
lianglijuan3710@dingtalk.com
Facility Information:
Facility Name
Shanghai Mengchao Cancer Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
201805
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Liang Lijuan, Bachelor
Phone
15618723710
Email
lianglijuan3710@dingtalk.com

12. IPD Sharing Statement

Learn more about this trial

Study of Efficacy of BZ019 in Large B-cell Lymphoma

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