search
Back to results

Clinical Study of U16 in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Primary Purpose

Relapsed or Refractory Non-Hodgkin's Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
U16
Sponsored by
Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed or Refractory Non-Hodgkin's Lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patients who are willing to sign the informed consent form and have good compliance; Aged 18-70 years, male or female; CD20-positive B-cell non-Hodgkin's lymphoma with immunohistochemistry(IHC), with the following diagnostic: Diffuse large B cell lymphoma (DLBCL), or Primary mediastinal large B cell lymphoma (PMBCL), or Follicular lymphoma transformed large B cell lymphoma (TFL) , or High grade B cell lymphoma(HGBCL); Previously received≥2nd-line adequate therapy or autologous hematopoietic stem cell transplantation (ASCT), including: a) Received anthracycline-containing drugs and rituximab or other CD20-targeted drugs (except CD20-negative tumors); b) Definition of line: Stable disease (SD) after receiving a first-line therapy for at least 4 cycles or progressive disease (PD), and SD after a second-line therapy for at least 2 cycles or PD; c) For transformed follicular lymphoma (TFL), patients must be treated adequately against FL, and after transformation, must have received at least once the therapy against TFL, and become relapsed or refractory after the last therapy; In relapsed or refractory status at screening: a) Definition of relapse: Remission (including partial remission (PR) or complete remission (CR)) after treatment with at least the standard therapy regimen, and then PD; b)Definition of refractory: i. Non-response to the last therapy: The best response by the last therapy is SD or PD, and the duration is less than 6 months; ii. Relapse or progression (it must be proved by biopsy) after ASCT, including: Relapse or PD within 12 months after ASCT; if a salvage therapy is received, the patient is non-response (SD or PD) to the last therapy; According to Lugano Criteria (Cheson2014), at least one measurable lesion exists; Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; Adequate bone marrow reserve, defined as: Absolute neutrophil count (ANC) ≥1.0×10^9/L; Absolute lymphocyte count (ALC) ≥ 0.3×10^9/L; Platelet (PLT) ≥50×10^9/L; Proper organ function, defined as: Aspartate aminotransferase (AST) ≤ 3 Upper Limit of Normal (ULN); Alanine aminotransferase (ALT) ≤ 3 ULN(AST and ALT≤5 ULN are required for the patients with hepatic dysfunction due to tumor cell infiltration) ; Total serum bilirubin ≤ 2 ULN, unless there exists concurrent Gilbert syndrome; patients with Gilbert syndrome, with total serum bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN, may be included; Serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula); Minimum pulmonary reserve, defined as Grade ≤ 1 dyspnea, and blood oxygen saturation > 91% at non-oxygen inhalation status; Women with child-bearing potential are negative in blood/urine pregnancy tests within 7 d prior to infusion of U16 infusion; any male or female patient with child-bearing potential must agree to adopt effective contraceptive measures throughout the study, and at least one year after administration of the investigational therapy. Qualified T cell function; Vascular conditions for apheresis, and no other contraindications for apheresis; Elution period of CD20 monoclonal antibody at least 3 months before U16 infusion; Life expectancy more than 3 months. Exclusion Criteria: Patients with other malignant tumors, except for disease-free survival for more than 3 years or carcinoma in-situ; Patients with lymphoma involved with atrium or ventricle; Used immunosuppressants, hormones or high-dose chemotherapy within 2 weeks before signing the informed consent form, or planned to use immunosuppressants or hormones(specifically referring to systemic therapy) before apheresis, except for local or inhaled corticosteroid therapy; Patients complying with any of hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg) positive; hepatitis B e antibody (HBe-Ab) and/or hepatitis B core antibody (HBc-Ab) positive and HBV-DNA copies being more than the lower limit of detection; hepatitis C antibody (HCV-Ab) positive and HBV-RNA copies being more than the lower limit of detection; anti-treponemia pallidum antibody (TP-Ab) positive; Human immunodeficiency virus (HIV) antibody positive; EBV-DNA, and CMV-DNA copies being more than the lower limit of detection; Patients with bacteria, fungi, viruses, mycoplasma or other types of infections, and difficult for controlling by researcher's judgment; Patients with active primary or secondary central nervous system (CNS) lymphoma (a patient with CNS disease symptoms must receive lumbar puncture to exclude CNS lymphoma); Patients with existing central nervous system disease or with a history of central nervous system disease, e.g., epileptic seizure, cerebral ischemia/hemorrhage, dementia, cerebellum disease, or any autoimmune disease involved with central nervous system; Patients with cardiac angioplasty or stent implantation within 12 months before signing the informed consent form, or myocardial infarction, unstable angina pectoris, other clinically significant heart disease history judged by researcher; Patients need urgent clinical emergencies (such as intestinal obstruction or vascular compression, etc.) due to the obstruction or compression of lymphoma judged by researcher; Patients previously received CAR-T cell therapy with CD20 target; Patients with primary immunodeficiency; Patients who are known with a history of hypersensitivity reaction to any ingredient used for the drug product in the trial.; Patients vaccinated with a live vaccine within 6 weeks prior to screening; Pregnant or lactating women; Patients with active autoimmune diseases; Patients with active acute or chronic graft-versus-host disease (GVHD) when signing the informed consent form; Received allogeneic hematopoietic stem cell transplantation within 6 months before signing the informed consent form; Participated in any other clinical trial within 30 days before signing the i informed consent form; Patients with other conditions that are not suitable to participate in the clinical trial, as considered by the investigator.

Sites / Locations

  • The Third Xiangya Hospital of Central South University
  • The First Affiliated Hospital of Soochow UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

U16

Arm Description

Route of administration: Intravenous injection. Lymphodepletion conditioning: Lymphodepletion will be conducted several days prior to U16 infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.

Outcomes

Primary Outcome Measures

Types, frequency and severity of adverse events
Safty of U16 as measured by types, frequency and severity of adverse events after U16 Injection infusion.
Overall Remission Rate (ORR)
Efficacy of U16 as measured by ORR during the 3 months after U16 Injection infusion, which includes CR and PR.

Secondary Outcome Measures

Complete Remission (CR)
Efficacy of U16 as measured by CR during the 3 months after U16 Injection infusion.
Progression-free survival (PFS)
PFS means duration from the U16 Injection infusion to progression of lymphoma, or death for any reason.
Duration of Remission (DOR)
DOR means the duration from reaching the response (e.g., CR or PR) criteria of the therapy to the first, clearly defined progressive disease, or death for disease under investigation.
Overall Survival(OS)
OS means duration from the U16 Injection infusion to death for any reason, or the last follow-up for survival.
Pharmacokinetic (PK)- Cmax
Maximum detected concentration of U16 in peripheral blood
Pharmacokinetic (PK)- Tmax
Time to maximum concentration of U16 in peripheral blood
Pharmacokinetic (PK)- AUC
Area under the concentration vs time curve of U16 in peripheral blood
Concentration of Cytokines in Serum
Collected as pharmacodynamic data, including IL-6 at least
Concentration of B cells
Measure B cells in peripheral blood

Full Information

First Posted
February 8, 2023
Last Updated
September 17, 2023
Sponsor
Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd
search

1. Study Identification

Unique Protocol Identification Number
NCT05768529
Brief Title
Clinical Study of U16 in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official Title
A Single-arm, Open and Multicenter Phase I/II Clinical Study to Evaluate the Safety and Efficacy of U16 Injection in the Treatment of Refractory/Recurrent B-cell Non-Hodgkin's Lymphoma (r/r B-NHL)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 28, 2023 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Unicar-Therapy Bio-medicine Technology 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
Yes

5. Study Description

Brief Summary
The study is a Phase I/II, single-arm, open-label clinical trial, and its primary objective of phase I and phase II is to evaluate the safety and efficacy of U16 Injection in the treatment of relapsed or refractory NHL,respectively.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed or Refractory Non-Hodgkin's Lymphoma

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
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
U16
Arm Type
Experimental
Arm Description
Route of administration: Intravenous injection. Lymphodepletion conditioning: Lymphodepletion will be conducted several days prior to U16 infusion. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
Intervention Type
Drug
Intervention Name(s)
U16
Intervention Description
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered before U16 treatment.
Primary Outcome Measure Information:
Title
Types, frequency and severity of adverse events
Description
Safty of U16 as measured by types, frequency and severity of adverse events after U16 Injection infusion.
Time Frame
24 months
Title
Overall Remission Rate (ORR)
Description
Efficacy of U16 as measured by ORR during the 3 months after U16 Injection infusion, which includes CR and PR.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Complete Remission (CR)
Description
Efficacy of U16 as measured by CR during the 3 months after U16 Injection infusion.
Time Frame
3 months
Title
Progression-free survival (PFS)
Description
PFS means duration from the U16 Injection infusion to progression of lymphoma, or death for any reason.
Time Frame
24 months
Title
Duration of Remission (DOR)
Description
DOR means the duration from reaching the response (e.g., CR or PR) criteria of the therapy to the first, clearly defined progressive disease, or death for disease under investigation.
Time Frame
24 months
Title
Overall Survival(OS)
Description
OS means duration from the U16 Injection infusion to death for any reason, or the last follow-up for survival.
Time Frame
24 months
Title
Pharmacokinetic (PK)- Cmax
Description
Maximum detected concentration of U16 in peripheral blood
Time Frame
24 months
Title
Pharmacokinetic (PK)- Tmax
Description
Time to maximum concentration of U16 in peripheral blood
Time Frame
24 months
Title
Pharmacokinetic (PK)- AUC
Description
Area under the concentration vs time curve of U16 in peripheral blood
Time Frame
24 months
Title
Concentration of Cytokines in Serum
Description
Collected as pharmacodynamic data, including IL-6 at least
Time Frame
24 months
Title
Concentration of B cells
Description
Measure B cells in peripheral blood
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who are willing to sign the informed consent form and have good compliance; Aged 18-70 years, male or female; CD20-positive B-cell non-Hodgkin's lymphoma with immunohistochemistry(IHC), with the following diagnostic: Diffuse large B cell lymphoma (DLBCL), or Primary mediastinal large B cell lymphoma (PMBCL), or Follicular lymphoma transformed large B cell lymphoma (TFL) , or High grade B cell lymphoma(HGBCL); Previously received≥2nd-line adequate therapy or autologous hematopoietic stem cell transplantation (ASCT), including: a) Received anthracycline-containing drugs and rituximab or other CD20-targeted drugs (except CD20-negative tumors); b) Definition of line: Stable disease (SD) after receiving a first-line therapy for at least 4 cycles or progressive disease (PD), and SD after a second-line therapy for at least 2 cycles or PD; c) For transformed follicular lymphoma (TFL), patients must be treated adequately against FL, and after transformation, must have received at least once the therapy against TFL, and become relapsed or refractory after the last therapy; In relapsed or refractory status at screening: a) Definition of relapse: Remission (including partial remission (PR) or complete remission (CR)) after treatment with at least the standard therapy regimen, and then PD; b)Definition of refractory: i. Non-response to the last therapy: The best response by the last therapy is SD or PD, and the duration is less than 6 months; ii. Relapse or progression (it must be proved by biopsy) after ASCT, including: Relapse or PD within 12 months after ASCT; if a salvage therapy is received, the patient is non-response (SD or PD) to the last therapy; According to Lugano Criteria (Cheson2014), at least one measurable lesion exists; Eastern Cooperative Oncology Group (ECOG) performance status of 0-1; Adequate bone marrow reserve, defined as: Absolute neutrophil count (ANC) ≥1.0×10^9/L; Absolute lymphocyte count (ALC) ≥ 0.3×10^9/L; Platelet (PLT) ≥50×10^9/L; Proper organ function, defined as: Aspartate aminotransferase (AST) ≤ 3 Upper Limit of Normal (ULN); Alanine aminotransferase (ALT) ≤ 3 ULN(AST and ALT≤5 ULN are required for the patients with hepatic dysfunction due to tumor cell infiltration) ; Total serum bilirubin ≤ 2 ULN, unless there exists concurrent Gilbert syndrome; patients with Gilbert syndrome, with total serum bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN, may be included; Serum creatinine ≤ 1.5 ULN or creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula); Minimum pulmonary reserve, defined as Grade ≤ 1 dyspnea, and blood oxygen saturation > 91% at non-oxygen inhalation status; Women with child-bearing potential are negative in blood/urine pregnancy tests within 7 d prior to infusion of U16 infusion; any male or female patient with child-bearing potential must agree to adopt effective contraceptive measures throughout the study, and at least one year after administration of the investigational therapy. Qualified T cell function; Vascular conditions for apheresis, and no other contraindications for apheresis; Elution period of CD20 monoclonal antibody at least 3 months before U16 infusion; Life expectancy more than 3 months. Exclusion Criteria: Patients with other malignant tumors, except for disease-free survival for more than 3 years or carcinoma in-situ; Patients with lymphoma involved with atrium or ventricle; Used immunosuppressants, hormones or high-dose chemotherapy within 2 weeks before signing the informed consent form, or planned to use immunosuppressants or hormones(specifically referring to systemic therapy) before apheresis, except for local or inhaled corticosteroid therapy; Patients complying with any of hepatitis B surface antigen (HBsAg) and/or hepatitis B e antigen (HBeAg) positive; hepatitis B e antibody (HBe-Ab) and/or hepatitis B core antibody (HBc-Ab) positive and HBV-DNA copies being more than the lower limit of detection; hepatitis C antibody (HCV-Ab) positive and HBV-RNA copies being more than the lower limit of detection; anti-treponemia pallidum antibody (TP-Ab) positive; Human immunodeficiency virus (HIV) antibody positive; EBV-DNA, and CMV-DNA copies being more than the lower limit of detection; Patients with bacteria, fungi, viruses, mycoplasma or other types of infections, and difficult for controlling by researcher's judgment; Patients with active primary or secondary central nervous system (CNS) lymphoma (a patient with CNS disease symptoms must receive lumbar puncture to exclude CNS lymphoma); Patients with existing central nervous system disease or with a history of central nervous system disease, e.g., epileptic seizure, cerebral ischemia/hemorrhage, dementia, cerebellum disease, or any autoimmune disease involved with central nervous system; Patients with cardiac angioplasty or stent implantation within 12 months before signing the informed consent form, or myocardial infarction, unstable angina pectoris, other clinically significant heart disease history judged by researcher; Patients need urgent clinical emergencies (such as intestinal obstruction or vascular compression, etc.) due to the obstruction or compression of lymphoma judged by researcher; Patients previously received CAR-T cell therapy with CD20 target; Patients with primary immunodeficiency; Patients who are known with a history of hypersensitivity reaction to any ingredient used for the drug product in the trial.; Patients vaccinated with a live vaccine within 6 weeks prior to screening; Pregnant or lactating women; Patients with active autoimmune diseases; Patients with active acute or chronic graft-versus-host disease (GVHD) when signing the informed consent form; Received allogeneic hematopoietic stem cell transplantation within 6 months before signing the informed consent form; Participated in any other clinical trial within 30 days before signing the i informed consent form; Patients with other conditions that are not suitable to participate in the clinical trial, as considered by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaoyan Lou, Dr.
Phone
18721281671
Email
xiaoyan.lou@unicar-therapy.com
First Name & Middle Initial & Last Name or Official Title & Degree
Liqing Kang, Dr.
Phone
13162512992
Email
liqing.kang@unicar-therapy.com
Facility Information:
Facility Name
The Third Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xin Li, Dr.
Phone
13808418932
Email
972978226@qq.com
Facility Name
The First Affiliated Hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Depei Wu, Dr.
Phone
0512-67781856
Email
wudepei@suda.edu.cn
First Name & Middle Initial & Last Name & Degree
Liqing Kang, Dr.
Phone
13162512992
Email
liqing.kang@unicar-therapy.com

12. IPD Sharing Statement

Learn more about this trial

Clinical Study of U16 in Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

We'll reach out to this number within 24 hrs