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

NCT05768529 | Recruiting Phase 1 DMC

• 1 other identifier: U16-I/II-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

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.

Conditions

Relapsed or Refractory Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (2)

• Types, frequency and severity of adverse events

  Safty of U16 as measured by types, frequency and severity of adverse events after U16 Injection infusion.

  24 months

• Overall Remission Rate (ORR)

  Efficacy of U16 as measured by ORR during the 3 months after U16 Injection infusion, which includes CR and PR.

  3 months

Secondary Outcomes (9)

• Complete Remission (CR)

  3 months

• Progression-free survival (PFS)

  24 months

• Duration of Remission (DOR)

  24 months

• Overall Survival（OS）

  24 months

• Pharmacokinetic (PK)- Cmax

  24 months

Study Arms (1)

U16

EXPERIMENTAL

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.

Drug: U16

Interventions

U16 DRUG

A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered before U16 treatment.

U16

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Trial participants voluntarily sign the informed consent form and have good compliance;
• Age ≥18 years and ≤70 years at the time of signing the informed consent form; male or female trial participants are eligible;
• Indication: B-cell non-Hodgkin lymphoma that is CD20-positive as demonstrated by immunohistochemistry (IHC) staining of prior tumor tissue samples or by bone marrow cells, and consistent with the 2017 WHO classification of NHL, including: diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (TFL) to large B-cell lymphoma, and high-grade B-cell lymphoma (HGBCL);
• Prior treatment with ≥2 lines of adequate therapy or autologous hematopoietic stem cell transplantation (ASCT). Adequate therapy includes: a) Must have received adequate treatment including anthracyclines and rituximab or other CD20-targeted agents (except for CD20-negative tumors); b) Lines of therapy: best response to first-line treatment was progressive disease (PD), or best response to at least 4 cycles of first-line treatment was stable disease (SD), or best response to at least 6 cycles of first-line treatment was PR; PD again during/after the last line of treatment (second-line or beyond), or best response to at least 2 cycles of the last line of treatment was SD. c) For TFL to large B-cell lymphoma: prior to transformation, the participant must have received adequate treatment for FL, and has relapsed or is refractory during/after the last line of treatment after transformation; if the initial diagnosis is transformed lymphoma, the participant must have received ≥2 lines of therapy and has relapsed or is refractory during/after the last line of treatment;
• In a state of disease relapse or refractoriness at screening: a) Definition of relapse: PD again after achieving response (including partial response (PR) or complete response (CR)) following adequate treatment; b) Definition of refractoriness: i. No response to the last treatment: PD during/after the last treatment or best response of SD with a duration of less than 6 months; ii. Relapse or progression after ASCT (confirmed by biopsy), including: relapse or PD within 12 months after ASCT; if salvage therapy was subsequently received, no response to the last treatment (SD or PD);
• According to the Lugano classification for lymphoma response assessment (Cheson 2014), at least 1 CT-measurable lesion (for nodal lesions: defined as long axis \>1.5 cm; for extranodal lesions: long axis should be \>1.0 cm), and a lesion confirmed positive by PET-CT;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1;
• Adequate bone marrow reserve at screening, defined as: absolute neutrophil count (ANC) ≥ 1.0×10⁹/L, absolute lymphocyte count (ALC) ≥ 0.3×10⁹/L, platelet count (PLT) ≥ 50×10⁹/L;
• Adequate organ function, meeting the following criteria: aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN); alanine aminotransferase (ALT) ≤3× ULN (for hepatic function abnormalities due to tumor infiltration, AST and ALT ≤5× ULN are required); total serum bilirubin ≤2× ULN, unless accompanied by Gilbert syndrome; trial participants with Gilbert syndrome who have total bilirubin ≤3× ULN and direct bilirubin ≤1.5× ULN may be enrolled. Serum creatinine ≤1.5× ULN, or creatinine clearance ≥60 mL/min (Cockcroft and Gault formula); minimum pulmonary reserve, defined as dyspnea ≤ grade 1 and oxygen saturation \>91% without supplemental oxygen;
• Women of childbearing potential must have a negative blood/urine pregnancy test within 7 days before U16 cell infusion; any male or female trial participant of reproductive potential must agree to use effective contraceptive methods throughout the entire study and for at least one year after administration of the study treatment;
• Adequate venous access for apheresis or venous blood collection, and no other contraindications to leukapheresis;
• Washout period for CD20-targeted agents of at least 6 weeks before screening (applicable to trial participants who have received rituximab or other CD20-targeted agents);
• Expected survival greater than 3 months.

You may not qualify if:

• Concurrent other malignancies, except for malignancies with disease-free survival exceeding 3 years and carcinoma in situ;
• Trial participants with lymphoma infiltration of the cardiac atria or ventricles;
• Use of immunosuppressants, high-dose chemotherapy within 2 weeks before signing the informed consent form, or use of hormones within 3 days, or planned requirement for immunosuppressants or hormones after signing the informed consent form and before/after apheresis; specifically referring to systemic therapy, excluding local or inhaled corticosteroid therapy;
• History of immunodeficiency, including human immunodeficiency virus (HIV) infection; positive anti-Treponema pallidum antibody (TP-Ab); hepatitis B virus infection (hepatitis B surface antigen \[HBsAg\] positive and hepatitis B virus deoxyribonucleic acid \[HBV-DNA\] quantification \> lower limit of detection); hepatitis C virus infection (hepatitis C virus \[HCV\] antibody positive and hepatitis C virus ribonucleic acid \[HCV-RNA\] quantification \> lower limit of detection);
• Presence of bacterial, fungal, viral, mycoplasma, or other types of infection that the investigator judges to be difficult to control;
• Presence of active primary or secondary central nervous system (CNS) lymphoma at screening (trial participants with symptoms of CNS disease must undergo lumbar puncture to rule out CNS lymphoma);
• Prior or current clinically significant CNS disease, such as seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any CNS-related autoimmune disease;
• Coronary angioplasty or stent placement within 12 months before signing the informed consent form, or myocardial infarction, unstable angina pectoris, or other clinically significant cardiac history as judged by the investigator; severe arrhythmia requiring treatment; left ventricular ejection fraction (LVEF) ≤50%; hypertension inadequately controlled despite standard treatment (systolic ≥160 mmHg and/or diastolic ≥100 mmHg) or pulmonary arterial hypertension;
• Trial participants with clinical emergencies requiring urgent management due to lymphoma tumor mass obstruction or compression as judged by the investigator (such as intestinal obstruction or vascular compression, etc.);
• Trial participants who have previously received CD20-targeted CAR-T therapy;
• History of severe immediate hypersensitivity reaction to any drug to be used in this study;
• Receipt of live vaccine within 6 weeks before screening;
• Pregnant or breastfeeding women;
• Active autoimmune disease;
• Presence of active acute or chronic graft-versus-host disease (GVHD) at the time of signing the informed consent form;

Sponsors & Collaborators

• Shanghai Unicar-Therapy Bio-medicine Technology Co.,Ltd: lead

Study Sites (3)

The Third Xiangya Hospital of Central South University

Changsha, Hunan, 410013, China

NOT YET RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Lymphoma, Non-Hodgkin

Interventions

LPAR4 protein, human

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Xiaoyan Lou, PhD

CONTACT

+86-18721281671; xiaoyan.lou@unicar-therapy.com

Liqing Kang, PhD

CONTACT

+86-13162512992; liqing.kang@unicar-therapy.com

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: February 8, 2023
• First Posted: March 14, 2023
• Study Start: March 28, 2023
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: October 2, 2026

Record last verified: 2026-09

Locations

CN (3)