CD30 CAR-T in the Treatment of CD30 Positive Lymphoma

The goal of this clinical trial is to explore the efficacy and safety of CD30 CAR-T on CD30 positive relapsed/refractory lymphoma. The main questions it aims to answer are:

To evaluate the safety and maximum tolerated dose of autologous CD30 CAR-T therapy in CD30-positive relapsed/refractory lymphoma; To evaluate the efficacy of autologous CD30 CAR-T therapy for CD30-positive relapsed/refractory lymphoma; To evaluate the metabolism of CD30 CAR-T cells in vivo; Preliminary evaluation of the correlation between CAR T cell dose and clinical efficacy.

• chimeric antigen receptor gene modified T cells (Drug): The rate of intravenous infusion of CD30 CAR T cells was 10 mL to 20 mL/min, and the infusion was performed using a blood transfusion apparatus with a filter screen. Use saline rinsing tube prior to infusion; Rinse the infusion bag with 10 mL\~30 mL normal saline.

Primary outcomes

• Incidence of Treatment-Emergent Adverse Events [28 days]: Incidence of DLTs and occurrence of study related adverse events

Secondary outcomes

• Overall response rate [3,6,12months]: Including complete remission (CR) and partial remission (PR)
• Overall Survival [3 years]: OS was calculated from the first CAR-T cell infusion to death or last follow-up
• Progression-free survival [3 years]: PFS was calculated from the first CAR-T cell infusion to death or rogression of the disease.

Other outcomes

• The copy number of CD30 CAR-T cells [12 months]: The copy number of CD30 CAR-T cells amplified in peripheral blood after administration

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Age≥18 years and ≤65years，female and male；
* CD30+ recurrent/refractory malignant hematological malignancies, experienced recurrence (disease progression after treatment remission) or refractory (previous systemic treatment did not achieve CR) after ≥ 2-line systemic treatment;
* CD30 expression >10% by immunohistochemistry；
* At least 1 measurable lesion can be measured according to theLugano 2014 evaluation criteria;
* The estimated survival time ≥3 months;
* ECOG performance status 0-2，KPS>60%;
* Sufficient organ function：ALT，AST≤2.5×ULN，patients with liver invasion can be relaxed to ≤ 5 x ULN；serum total bilirubin<34 μmol/L；creatinine clearance rate>30 mL/min；EF≥40%；No pericardial effusion and obvious arrhythmia；SpO2≥92%；
* ALC ≥0.5×109/L，PLT>30×109/L，Hb>80 g/L and subjects had apheresis venous access and no contraindications for blood cell separation;
* MRI showed no central involvement of lymphoma;
* Patients with fertility must be willing to be able to use reliable contraceptive measures ;
* The subject or legal guardian can understand and voluntarily sign the written informed consent.

Exclusion Criteria:

* Lymphoma-associated hemophagic cell syndrome;
* Pregnant or lactating women, and women who have a pregnancy plan within six months;
* Hepatitis B（HBsAg、HBsAb、HBeAg、HBeAb、HBcAb），Hepatitis C（Anti-HCV），Anti-HIV Ⅰ/Ⅱ and anti-TP positive（Hepatitis B DNA test is negative except）;
* Suffered from other malignant tumors, except for for skin basal cell carcinoma, skin squamous cell carcinoma and cervical carcinoma in situ undergoing the radical treatment;
* Received Anti-CD30 Ab therapy within 4 weeks before enrollment;
* Unresolved > Grade 1 non-hematologic toxicity associated with any prior treatments;
* Active uncontrolled bleeding or a known bleeding diathesis;
* Autologous hematopoietic stem cell transplantation was performed within 6 weeks;
* Uncontrollable active bacterial or fungal infection；
* Known allergy to the study drug and its components;
* Suffer from active autoimmune diseases that require systemic treatment ;
* Persons with mental or mental illness who cannot cooperate with treatment and efficacy evaluation;
* Participated in other clinical studies within 1 months prior to this study;
* History of allogeneic hematopoietic stem cell transplantation;
* patients with any condition which the investigator or treating physician feels would interfere with the trial or the safety of the subject.