Actively Recruiting

Phase 1
Phase 2
Age: 18Years - 75Years
All Genders
NCT06321289

Allogeneic TRAC Locus-inserted CD19-targeting STAR T Cell Therapy in r/r B-NHL

Led by Chinese PLA General Hospital · Updated on 2024-03-25

30

Participants Needed

2

Research Sites

156 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

The team has developed the synthetic T cell receptor (TCR) and antigen receptor (STAR) T cells which were demonstrated safety in relapsed or refractory (r/r) B-cell non-Hodgkin' s lymphoma (B-NHL) (NCT05631912). Based on this research, allogeneic STAR-T cell products utilized the CRISPR-Cas9 gene editing tool to knock out endogenous receptor α constant (TRAC), human leukocyte antigen (HLA)-A/B, CIITA, and programmed death 1 (PD-1) genes simultaneously in T cells from healthy donors, and integrated the STAR molecule into the TRAC locus using adenovirus associated virus. This strategy can reduce graft-versus-host-disease (GvHD) toxicity and host-versus-graft response, decrease the sensitivity of STAR T cells to immunosuppressive signals, and improve their anti-tumor activity. In this single center, prospective, open-label, single-arm, phase 1/2 study, the safety and efficacy of allogeneic CD19-targeting STAR T cell therapy will be evaluated in patients with r/r B-NHL.

CONDITIONS

Official Title

Allogeneic TRAC Locus-inserted CD19-targeting STAR T Cell Therapy in r/r B-NHL

Who Can Participate

Age: 18Years - 75Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 18 to 75 years inclusive
  • Histologically confirmed CD19-positive B-cell non-Hodgkin's lymphoma, including DLBCL-NOS, PMBCL, TFL, HGBCL, FL, MCL, and MZL
  • Relapsed after 2 or more systemic therapies or refractory disease for aggressive lymphoma types
  • Adequate prior therapy including anthracycline or bendamustine chemotherapy and anti-CD20 monoclonal antibody (with exceptions for CD20-negative tumors)
  • Estimated survival time greater than 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  • At least one evaluable tumor focus meeting size criteria by CT or MRI
  • Willingness to undergo tumor biopsy or provide tumor tissue samples
  • Adequate organ function including heart, kidney, liver, and lung function as specified
  • Blood counts meeting specified minimum levels without growth factor support
  • Negative pregnancy test for women of childbearing potential; agreement to use effective contraception during treatment and for 1 year after
  • Toxicity from prior therapies must be grade 1 or less or acceptable according to criteria
  • No significant hereditary diseases
  • Ability to understand and willing to participate in the study
  • Signed informed consent
Not Eligible

You will not qualify if you...

  • Presence or history of central nervous system invasion or significant CNS diseases such as epilepsy or cerebrovascular disease
  • Pregnancy or breastfeeding, or refusal to use contraception during treatment and 1 year after
  • History of allogeneic hematopoietic stem cell or organ transplantation
  • History of other active malignancies not in remission
  • Primary immunodeficiency or autoimmune diseases requiring immunosuppressive therapy
  • Radiotherapy within 3 months prior to enrollment
  • Immunotherapy within 4 weeks prior to enrollment
  • Positive anti-CD19 scFv reaction in serum
  • Prior CD19-targeted therapy or CAR-T/genetically modified T cell therapy
  • Presence of donor-specific antibodies against STAR T cells
  • Participation in other clinical trials within 4 weeks prior to enrollment
  • Uncontrolled infections or serious illnesses including HIV or active hepatitis
  • Uncontrollable serous membrane fluid such as massive pleural effusion or ascites
  • Stroke or intracranial hemorrhage within 3 months prior to enrollment
  • Major surgery or trauma within 28 days prior or unresolved major side effects
  • Allergy to ingredients in cell products
  • Mental or physical conditions interfering with study participation or data interpretation
  • Investigator judgment that participation poses significant risk or interferes with study
  • Inability or unwillingness to provide informed consent
  • Other reasons deemed unsuitable by investigators

AI-Screening

AI-Powered Screening

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Trial Site Locations

Total: 2 locations

1

Biotherapeutic Department of Chinese PLA General Hospital

Beijing, Beijing Municipality, China, 100853

Actively Recruiting

2

School of medicine, Tsinghua University & Changping Laboratory

Beijing, China

Actively Recruiting

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Research Team

W

Weidong Han, Ph.D

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SEQUENTIAL

Primary Purpose

TREATMENT

Number of Arms

1

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