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Large B-cell LymphomaPhase 1NCT04250324

Study of Safety and Efficacy of BZ019 in (R/R) Large B-cell Lymphoma

A Phase 1 study testing BZ019 in people with Large B-cell Lymphoma, run by Shanghai Cell Therapy Group Co.,Ltd at 2 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

This is an open-label, multicenter, dose-escalation phase 1 study to determine the Safety and Efficacy of BZ019 in relapsed or refractory CD19+ B-cell Lymphoma subjects. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Large B-cell Lymphoma
What is being tested?
BZ019
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
2 sitesChina
Study dates
19 Nov 2019to Dec 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Written informed consent must be obtained prior to any screening procedures;
  • Age ≥ 18 years subjects with Relapsed or refractory large B-cell lymphoma, only DLBCL non-specific type, primary mediastinal large B-cell lymphoma, follicular lymphoma transformed large B-cell lymphoma, advanced B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement, advanced B-cell lymphoma non-specific type. The definition of refractory is as follows:
  • no response to the last treatment, including:The best response to the latest treatment is disease progression (PD), or the best response to the latest treatment plan is disease stability (SD) and the maintenance time is not more than 6 months after the last administration;
  • or not suitable for autologous hematopoietic stem cell transplantation (ASCT), or ASCT refractory, including: 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.
  • 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:
  • Treatment by CD20 monoclonal antibody (Rituximab) except for CD20 negative;
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  • a chemotherapy regimen containing anthracyclines.
  • 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.
  • Life expectancy ≥12 weeks.
  • Baseline Eastern Cooperative Oncology Group (ECOG) score is 0 or 1 .
  • Adequate organ function:
  • Renal function defined as:A serum creatinine of ≤1.5 x ULN or Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73 m^2;
  • 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;
  • Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation > 91% on room air.
  • Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) ≥ 50%, confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA).
  • No blood transfusion within 1 week before signing the informed consent, sufficient bone marrow reserve is available, which is defined as:
  • Absolute neutrophil count (ANC) > 1000/μl;
  • Absolute lymphocyte count (ALC) ≥ 500/μl;
  • Platelets ≥ 50000/μl;
  • Hemoglobin > 8.0 g/dl, for patients with bone marrow invasion, hemoglobin > 6.0 g/dl can be considered into the group.
  • Must have an apheresis product of non-mobilized cells accepted for manufacturing.
  • If the patient uses the following drugs, the following conditions should be met:
  • 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;
  • Immunosuppression: Any immunosuppressive medication must be stopped ≥ 4 weeks prior to enrollment;
  • Antiproliferative therapies other than lymphodepleting chemotherapy within two weeks of infusion
  • Antibody use including anti-CD20 therapy within 4 weeks prior to infusion or 5 half-lives of the respected antibody, whichever is longer
  • CNS disease prophylaxis must be stopped > 1 week prior to BZ019 infusion (e.g. intrathecal methotrexate)
  • 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).

Who cannot join

  • 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.
  • Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of infusion.
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  • Investigational medicinal product within the last 30 days prior to screening.
  • Prior radiation therapy within 6 weeks of infusion.
  • 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 protocol-related inclusion/exclusion may apply.

Trial locations and contacts

2 sites in 1 country.

Yan Sun, M.D contact

021-59593168

suny@shcell.org

Zhicai Lin, M.D contact

021-59593168

linzc@shcell.org

China2 sites, 2 recruiting

  • Hematology Hospital, Chinese Academy of Medical Sciences

    Tianjin, 300020

    Lugui Qiu, prof., 022-23909282, qiulg@ihcams.ac.cn

    Recruiting

  • Tianjin medical university cancer institute and hospital

    Tianjin, 300060

    Lanfang Li, prof., 022-23340123 ext. 3210, lilanfangmeng@163.com

    Recruiting

Other trials in China

About this study

Official title: A Phase I Clinical Study of CD19-targeted Chimeric Antigen Receptor (CAR) T Cells Injection, for Relapsed and Refractory (R/R) Large B-cell Lymphoma

This is an open-label, multicenter, dose-escalation phase 1 study to determine the Safety and Efficacy of BZ019 in relapsed or refractory CD19+ B-cell Lymphoma subjects.

Read the detailed description

This is an open-label, multicenter, phase 1 study to determine the safety, PK, and antitumor activity of BZ019 in adult subjects with R/R large CD19+B cell lymphoma. The safety and efficacy of a single dose of different target doses of BZ019 will be evaluated in the dose-escalation phase and dose-expansion phase.

Primary objectives:

  • To evaluate the safety and tolerance of single infusion of BZ019 in adult patients with relapsed or refractory large B-cell lymphoma, and to determine the maximum tolerable dose (MTD) and phase II recommended dose.

Secondary objectives：

  • To evaluate the pharmacokinetics and survival of BZ019 in the peripheral blood of adult patients with relapsed or refractory large B-cell lymphoma;
  • To evaluate the Pharmacodynamic characteristics of BZ019 in adult patients with relapsed or refractory large B-cell lymphoma;
  • Objective response rate (ORR), Overall survival, progression free survival, event free survival, and tumor progression time were used to evaluate the antitumor efficacy of BZ019 in the treatment of relapsed or refractory large B-cell lymphoma.
Being tested
BZ019

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BZ019Biological

    A treatment program will include lymphodepleting chemotherapy with fludarabine and cyclophosphamide (flu/cy) followed by single-dose of BZ019 administered intravenously (IV).

Study groups in NCT04250324
Study groupRoleWhat they receive
BZ019ExperimentalThe subjects are enrolled into 2 dose-escalation cohorts, include 3x10^6/kg、6x10^6/kg, and dose-expansion cohorts, maybe 8x10^6/kg、10x10^6/kg.
Receives: Biological: BZ019

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose-limiting toxicity (DLT)

    Safety

    Measured: After 28 days of single infusion

  2. Maximum tolerated dose (MTD)

    Tolerability

    Measured: After 28 days of single infusion

Secondary outcomes (8)

  1. Pharmacokinetics（the copies of cells in vivo）

    Pharmacokinetics is defined as the number of copies of BZ019 DNA in peripheral blood at each visit after infusion until the test results are negative or below the detection limit. It aims to calculate the Peak Plasma Concentration (Cmax)

    Measured: Month 24

  2. Pharmacokinetics（the duration of survival of cells in vivo）

    Duration of BZ019 persistence is the period from the day of infusion to the first negative test result. It aims to calculate the area under the plasma concentration versus time curve (AUC)

    Measured: Month 24

  3. Pharmacodynamics

    Pharmacodynamics is defined as the level of Cytokine, at least include IL-2, IL-4, IL-6, IL-10, IL-15, IFN-γ, TNF-α. The peak value of cytokines and their return to baseline were evaluated

    Measured: After 28 days of single infusion

  4. Antitumor efficacy-Objective response rate (ORR)

    The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%)

    Measured: Month 24

  5. Antitumor efficacy-Overall survival (OS)

    The period from the first infusion to any cause of death

    Measured: Month 24

  6. Antitumor efficacy-Progression-free survival (PFS)

    The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first.

    Measured: Month 24

  7. Antitumor efficacy-event -free survival (EFS)

    Event free survival rate refers to the time from enrollment to occurrence of any event, including death, disease progression, change of chemotherapy program, change to chemotherapy, additional treatment, occurrence of lethal or intolerable side effects and other events.

    Measured: Month 24

  8. Antitumor efficacy- Tumor progression time (TTP)

    Tumor progression time refers to the time from the beginning of the infusion of cells to tumor progression

    Measured: Month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jan 2020
  2. Study start19 Nov 2019
  3. Primary completionAug 2022 (estimated)
  4. Study completionDec 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04250324
Sponsor's protocol ID
XY2019028-EC-1
Status last verified
Jan 2020
First submitted
30 Jan 2020
Last updated
31 Jan 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BZ019 in people with Large B-cell Lymphoma, run by Shanghai Cell Therapy Group Co.,Ltd at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 31 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Yan Sun, M.D (021-59593168, suny@shcell.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting toxicity (DLT) (time frame: After 28 days of single infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04250324.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2020.

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