CD147-CAR T Cells for Relapsed/Refractory T Cell Non-Hodgkin's Lymphoma

NCT ID: NCT05013372

Last Updated: 2022-08-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-31
• Study Completion Date: 2025-01-01

Brief Summary

The safety and preliminary effectiveness of CD147-CAR T cells in patients with relapsed or refractory T cell non-Hodgkin's lymphoma will be investigated in this pioneering study.

Detailed Description

CD147 has been demonstrated higher and relatively specific expression on T cell non-Hodgkin's lymphoma. Preclinical studies have shown that CAR T cells targeting CD147 antigen can continuously eliminate Jurkat T-cell lymphoma in mice and extend survival without severe adverse events including hemolysis. Preliminary investigation of CD147-CAR T cells in solid tumors has started and shown an acceptable safety profile. The safety and preliminary effectiveness of CD147-CAR T cells in patients with relapsed or refractory T cell non-Hodgkin's lymphoma will be investigated in this pioneering study.

Conditions

T-cell Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose-escalation

Dose -1：0.1×10E+6/kg Dose 1：0.25×10E+6/kg Dose 2：0.5×10E+6/kg Dose 3：1.0×10E+6/kg Dose 4：2.0×10E+6/kg

Group Type: OTHER

CD147- CAR T cells

Intervention Type: DRUG

CAR T cells targeting CD147

Interventions

CD147- CAR T cells

CAR T cells targeting CD147

Intervention Type: DRUG

Other Intervention Names

CAR T cells targeting CD147

Eligibility Criteria

Inclusion Criteria

• The subject must meet all of the following criteria:

1. 18-65 years old;

2. Relapsed or refractory T-NHLs, including peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), ALK-positive ALCL, ALK-negative Image result for anaplastic large cell lymphoma (ALCL), enteropathy-related T-cell lymphoma, hepatosplenic T-cell lymphoma, etc.;

3. Previously received ≥2 lines of treatment without a complete response;

4. Immunohistochemical detection of tumor cells CD147 positive;

5. ECOG score 0-2;

6. The collection of mononuclear cells can be performed upon the judgment of the researcher;

7. No contraindications for allogeneic hematopoietic stem cell transplantation (AlloHCT);

8. Have donors for AlloHCT;

9. Agree for sequential treatment of AlloHCT;

10. Without serious organ dysfunction in 2 weeks before CAR-T infusion:

1. Heart: without arrhythmia, LVEF≥50%, and without pericardial effusion; without heart failure (NYHA class III or IV) within12 months before CAR-T infusion; without myocardial infarction within 12 months before CAR-T infusion; without long-QT syndrome or secondary QT interval prolongation;

2. Liver: ALT<2 times the upper limit of normal (ULN) and TBIL<1.5 times ULN, without active hepatitis;

3. APTT and PT<1.5 times ULN;

4. Kidney: Serum creatinine <1.5 mg/dl; or if the serum creatinine exceeds the upper limit, eGFR (CKD-EPI formula) needs to be > 50 ml/min;

5. Fingertip blood oxygen saturation ≥ 92%.

11. Estimated survival ≥ 3 months;

12. Sexually active patients must be willing to use an effective method of birth control during the study period and within 6 months after the study ending, and male partners should use condoms;

13. The patient is willing to join this clinical trial and sign an informed consent.

Exclusion Criteria

• Anyone who has one or more of the following:

1. A history of other malignancies with a disease-free period < 5 years (except for cured basal cell carcinoma of the skin, cured cervical carcinoma in situ, and gastrointestinal tumors proven to be cured by endoscopic mucosal resection);

2. Those who have received allogeneic hematopoietic stem cell transplantation or organ transplantation;

3. Patients with bone marrow involvement;

4. Those who are allergic to the biological agents in CAR-T cell product ;

5. Pregnant or breastfeeding;

6. Active bacterial, fungal or viral infection;

7. Receiving systemic hormone therapy 1 week before participating in the clinical trial;

8. Have received other gene therapy before;

9. HBV or HCV infection or carrier is defined as: HBsAg positive or HBV-DNA positive; anti-HCV positive and HCV-RNA positive;

10. Active HIV infection;

11. Clinical diagnosis of virus infection or uncontrolled virus activation, including cytomegalovirus (CMV), adenovirus (ADV), BK virus or human herpesvirus 6 (HHV-6), etc.;

12. Central nervous system lymphoma (CNSL) is defined as the presence of ≥5 tumor cells/ ul in cerebrospinal fluid (CSF) or MRI suggested CNSL; any other CNS diseases, such as uncontrolled epilepsy, cerebral ischemia/hemorrhage, dementia, cerebellar disease or any autoimmune disease involving the central nervous system, or received treatment for central nervous system or brain metastasis (radiotherapy, surgery or other treatments);

13. Imaging determined lung infection;

14. Inappropriate to participate in the trial with investigators' decision.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Xiao-Jun Huang

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xiaojun Huang, MD. PhD.

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Central Contacts

Shenmiao Yang, MD.

Role: CONTACT

yangshenmiao@hotmail.com

13439999810

Xiaojun Huang, MD. PhD.

Role: CONTACT

Other Identifiers

CD147-CAR T for R/R T-NHL

Identifier Type: -

Identifier Source: org_study_id