Study of Efficacy of BZ019 in Large B-cell Lymphoma
Study Details
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: BZ019 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). |
Biological: BZ019
A treatment program will include lymphodepleting chemotherapy with fludarabine and cyclophosphamide (flu/cy) followed by single-dose of BZ019 administered intravenously (IV).
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Outcome Measures
Primary Outcome Measures
- Objective response rate (ORR) [Month 3]
Clinical response will be assessed by RECIST 1.1.
Secondary Outcome Measures
- Pharmacokinetics (PK) [Month 12]
Peak Plasma Concentration (Cmax)
- Pharmacodynamics (PD) [Month 12]
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) [Month 12]
Quality of life will be assessed by EQ-5D health Index scale
Eligibility Criteria
Criteria
Inclusion Criteria:
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1)Written informed consent must be obtained prior to any screening procedures;
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2)75 ≥Age ≥ 18 years subjects;
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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:
- 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.
- CD19+ which was detected by immunocytochemistry or flow cytometric ;
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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;
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- Life expectancy ≥12 weeks;
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6)Baseline Eastern Cooperative Oncology Group (ECOG) score is 0 or 2 Baseline Eastern Cooperative Oncology Group (ECOG) score is 0 or 2 ;
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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:
- 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;
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8)Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) ≥ 50%, confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA);
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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) >1x109/L; B)Absolute lymphocyte count (ALC) ≥ 0.5x109/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;
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10)Must have an apheresis product of non-mobilized cells accepted for manufacturing;
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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);
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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:
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• Patients who have previously received any anti-CD45, anti-CD19 or anti-CD3 therapy;
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Patients who have previously received any adoptive T cell therapy or gene therapy products, including CAR-T therapy;
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Active Central Nervous System (CNS) involvement by malignancy or secondary CNS involvement
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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.
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Prior allogeneic HSCT.
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Patients with positive hepatitis B (HBsAg and / or HBcAb positive, except for those with positive surface antibody alone) or hepatitis C serological markers;
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HIV positive or Treponema pallidum positive patients.
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Patients with uncontrollable active or life-threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours before infusion);
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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:
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Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)
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In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study
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A primary malignancy which has been completely resected and in complete remission for ≥ 5 years
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Pregnant or nursing (lactating) women.
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Patients with uncontrolled arrhythmia.
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Patients on oral anticoagulation therapy within 1 week prior to BZ019 infusion.
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Patients with active neurological auto immune or inflammatory disorders(e.g. Guillain Barre Syndrome, Amyptrophic Lateral Sclerosis)
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Other conditions, such as compliance, that the investigators consider should not be included in this clinical trial.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Shanghai Mengchao Cancer Hospital | Shanghai | Shanghai | China | 201805 |
Sponsors and Collaborators
- Shanghai Mengchao Cancer Hospital
- Shanghai Cell Therapy Group Co.,Ltd
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BZ019R-A-01