CD147-CAR T Cells for Relapsed/Refractory T Cell Non-Hodgkin's Lymphoma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: 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 |
Drug: CD147- CAR T cells
CAR T cells targeting CD147
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Maximum tolerated dose (MTD) [within 12 months]
The highest dose that does not cause unacceptable side effects.
- Dose-limiting toxicity (DLT) [within 12 months]
Side effects serious enough to prevent an increase in dose.
- Adverse events [within 12 months]
Adverse events
- Serious adverse events (SAE) [within 12 months]
Serious adverse events (SAE)
- Adverse events of special interest (AESI) [within 12 months]
Secondary Outcome Measures
- Overall response rate (ORR) [At the 12th week, 6th month, 9th month and 12th month]
Overall response rate (ORR) evaluated according to the Lugano2014 criteria
- Complete response rate (CR) [At the 12th week, 6th month, 9th month and 12th month]
Complete response rate (CR) evaluated according to the Lugano2014 criteria
- Duration of response (DOR) [At the 12th week, 6th month, 9th month and 12th month]
Duration of response (DOR)
- 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]
Eligibility Criteria
Criteria
Inclusion Criteria:
- The subject must meet all of the following criteria:
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18-65 years old;
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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.;
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Previously received ≥2 lines of treatment without a complete response;
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Immunohistochemical detection of tumor cells CD147 positive;
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ECOG score 0-2;
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The collection of mononuclear cells can be performed upon the judgment of the researcher;
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No contraindications for allogeneic hematopoietic stem cell transplantation (AlloHCT);
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Have donors for AlloHCT;
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Agree for sequential treatment of AlloHCT;
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Without serious organ dysfunction in 2 weeks before CAR-T infusion:
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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;
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Liver: ALT<2 times the upper limit of normal (ULN) and TBIL<1.5 times ULN, without active hepatitis;
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APTT and PT<1.5 times ULN;
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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;
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Fingertip blood oxygen saturation ≥ 92%.
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Estimated survival ≥ 3 months;
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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;
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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:
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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);
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Those who have received allogeneic hematopoietic stem cell transplantation or organ transplantation;
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Patients with bone marrow involvement;
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Those who are allergic to the biological agents in CAR-T cell product ;
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Pregnant or breastfeeding;
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Active bacterial, fungal or viral infection;
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Receiving systemic hormone therapy 1 week before participating in the clinical trial;
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Have received other gene therapy before;
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HBV or HCV infection or carrier is defined as: HBsAg positive or HBV-DNA positive; anti-HCV positive and HCV-RNA positive;
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Active HIV infection;
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Clinical diagnosis of virus infection or uncontrolled virus activation, including cytomegalovirus (CMV), adenovirus (ADV), BK virus or human herpesvirus 6 (HHV-6), etc.;
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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);
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Imaging determined lung infection;
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Inappropriate to participate in the trial with investigators' decision.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Peking University People's Hospital
Investigators
- Principal Investigator: Xiaojun Huang, MD. PhD., Peking University People's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CD147-CAR T for R/R T-NHL