T-cell Non-Hodgkin's Lymphoma
Conditions
Keywords
CAR T cells, T-cell Non-Hodgkin's lymphoma, CD147
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.
Interventions
DRUGCD147- CAR T cells
CAR T cells targeting CD147
Sponsors
Peking University People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| AUC of CD147-CAR T cells | within 4 weeks | — |
| 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 | — |
Contacts
Primary ContactShenmiao Yang, MD.
Backup ContactXiaojun Huang, MD. PhD.
Outcome results
None listed