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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Pioneering Study on the Safety and Efficacy of CD147-Chimeric Antigen Receptor (CAR) T Cells in Patients With Relapsed or Refractory T-cell Non-Hodgkin's Lymphoma

Conditions
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T-cell Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: CD147- CAR T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject must meet all of the following criteria: 18-65 years old; 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.; Previously received ≥2 lines of treatment without a complete response; Immunohistochemical detection of tumor cells CD147 positive; ECOG score 0-2; The collection of mononuclear cells can be performed upon the judgment of the researcher; No contraindications for allogeneic hematopoietic stem cell transplantation (AlloHCT); Have donors for AlloHCT; Agree for sequential treatment of AlloHCT; Without serious organ dysfunction in 2 weeks before CAR-T infusion: 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; Liver: ALT<2 times the upper limit of normal (ULN) and TBIL<1.5 times ULN, without active hepatitis; APTT and PT<1.5 times ULN; 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; Fingertip blood oxygen saturation ≥ 92%. Estimated survival ≥ 3 months; 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; 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: 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); Those who have received allogeneic hematopoietic stem cell transplantation or organ transplantation; Patients with bone marrow involvement; Those who are allergic to the biological agents in CAR-T cell product ; Pregnant or breastfeeding; Active bacterial, fungal or viral infection; Receiving systemic hormone therapy 1 week before participating in the clinical trial; Have received other gene therapy before; HBV or HCV infection or carrier is defined as: HBsAg positive or HBV-DNA positive; anti-HCV positive and HCV-RNA positive; Active HIV infection; Clinical diagnosis of virus infection or uncontrolled virus activation, including cytomegalovirus (CMV), adenovirus (ADV), BK virus or human herpesvirus 6 (HHV-6), etc.; 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); Imaging determined lung infection; Inappropriate to participate in the trial with investigators' decision.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Dose-escalation<br>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 | Drug: CD147- CAR T cells<br>* CAR T cells targeting CD147<br>* Other names: CAR T cells targeting CD147;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) | The highest dose that does not cause unacceptable side effects. | within 12 months | 
| Dose-limiting toxicity (DLT) | Side effects serious enough to prevent an increase in dose. | within 12 months | 
| Adverse events | Adverse events | within 12 months | 
| Serious adverse events (SAE) | Serious adverse events (SAE) | within 12 months | 
| Adverse events of special interest (AESI) |  | within 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Overall response rate (ORR) evaluated according to the Lugano2014 criteria | At the 12th week, 6th month, 9th month and 12th month | 
| Complete response rate (CR) | Complete response rate (CR) evaluated according to the Lugano2014 criteria | At the 12th week, 6th month, 9th month and 12th month | 
| Duration of response (DOR) | Duration of response (DOR) | At the 12th week, 6th month, 9th month and 12th month | 
| Cmax of CD147-CAR T cells |  | within 4 weeks | 
| Tmax of CD147-CAR T cells |  | within 4 weeks | 
| AUC of CD147-CAR T cells |  | within 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CD147, CAR T cells, T-cell Non-Hodgkin's lymphoma