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

NCT04250324 | Unknown Phase 1 DMC

• 1 other identifier: XY2019028-EC-1
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT)

  Safety

  After 28 days of single infusion

• Maximum tolerated dose (MTD)

  Tolerability

  After 28 days of single infusion

Secondary Outcomes (8)

• Pharmacokinetics（the copies of cells in vivo）

  Month 24

• Pharmacokinetics（the duration of survival of cells in vivo）

  Month 24

• Pharmacodynamics

  After 28 days of single infusion

• Antitumor efficacy-Objective response rate (ORR)

  Month 24

• Antitumor efficacy-Overall survival (OS)

  Month 24

Study Arms (1)

BZ019

EXPERIMENTAL

The 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.

Biological: BZ019

Interventions

BZ019 BIOLOGICAL

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

BZ019

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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).

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Shanghai Cell Therapy Group Co.,Ltd: lead
• Institute of Hematology & Blood Diseases Hospital, China: collaborator
• Tianjin Medical University Cancer Institute and Hospital: collaborator

Study Sites (2)

Hematology Hospital, Chinese Academy of Medical Sciences

Tianjin, 300020, China

RECRUITING

Tianjin medical university cancer institute and hospital

Tianjin, 300060, China

RECRUITING

Study Officials

• Lugui Qiu, Ph.D

  Hematology Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yan Sun, M.D

CONTACT

021-59593168; suny@shcell.org

Zhicai Lin, M.D

CONTACT

021-59593168; linzc@shcell.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2020
• First Posted: January 31, 2020
• Study Start: November 19, 2019
• Primary Completion: August 1, 2022
• Study Completion: December 1, 2022
• Last Updated: January 31, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)