Clinical Study of SenL-T7 CAR T Cells in the Treatment of Relapsed and Refractory CD7+ T-cell Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

Study Overview
=================
Brief Summary
-----------------
This is an open, single-arm, clinical study to evaluate efficacy and safety of anti CD7 CAR-T cell in the treatment of relapsed and refractory CD7+ T-cell lymphoblastic leukemia or T-cell lymphoblastic lymphoma

Detailed Description
-----------------
This study is an open, prospective, dose-increasing clinical study with patients with relapsed or refractory CD7+ T-cell lymphoblastic leukemia or T-cell lymphoblastic lymphoma as subjects. In order to evaluate the safety and efficacy of SENL-T7 in patients with CD7+ T-cell lymphoblastic leukemia or T-cell lymphoblastic lymphoma, the PK/PD indicators of SENL-T7 are also collected. In this study, no dose grouping is set, and 0.5-2E6 /kg× actual body weight dose is selected for reinfusion according to patients' disease diagnosis and tumor load. The Main research objectives: To evaluate the safety and efficacy of SENL-T7 in patients with relapsed or refractory CD7+ T-cell lymphoblastic leukemia or T-cell lymphoblastic lymphoma. The Secondary research objectives: To investigate the cellular dynamics of SENL-T7 CAR T cells in patients with relapsed or refractory CD7+ T-cell lymphoblastic leukemia or T-cell lymphoblastic lymphoma.

Official Title
-----------------
Clinical Study of SenL-T7 CAR T Cells in the Treatment of Relapsed and Refractory CD7+ T-cell Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

Conditions
-----------------
SenL-T7 CAR T Cells for CD7+ T-cell Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

Intervention / Treatment
-----------------
* Biological: Senl-T7


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of relapsed/refractory T-cell lymphoblastic leukemia or T-cell lymphoblastic lymphoma: Induction therapy failed to achieve a complete remission of minor residual negative; Recurrence: after complete remission, any tumor load in the peripheral blood or bone marrow was 5%, or slightly residual positive, or new extramedullary lesions occurred； CD7 expression in tumor cells was detected by flow cytometry； Life expectancy greater than 12 weeks； KPS or Lansky score≥60; HGB≥70g/L (can be transfused); 2-70 years old; oxygen saturation of blood#90%#; Total bilirubin (TBil)≤3 × upper limit normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal; Informed consent explained to, understood by and signed by patient/ guardian. Exclusion Criteria: Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF (left ventricular shortening fraction)<30% or LVEF(left ventricular ejection fraction)<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA(New York Heart Association) III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment); Has an active GvHD; Has a history of severe pulmonary function damaging; With other tumors which is/are in advanced malignant and has/have systemic metastasis; Severe or persistent infection that cannot be effectively controlled; Merging severe autoimmune diseases or immunodeficiency disease; Patients with active hepatitis B or hepatitis C([HBVDNA+]or [HCVRNA +]); Patients with HIV infection or syphilis infection; Has a history of serious allergies on Biological products (including antibiotics); Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BKvirus, or HHV(human herpesvirus)-6. Presence of symptomatic disorders of the central nervous system, which include but not limited to uncontrolled epilepsy, cerebrovascular ischemia/hemorrhage, dementia, and cerebellar disease, etc.; Have received transplant treatment for less than 6 months in prior to enrollment; Being pregnant and lactating or having pregnancy within 12 months; Any situations that the researchers believe will increase the risks for the subject or affect the results of the study.

Ages Eligible for Study
-----------------
Minimum Age: 2 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD7 CAR-T<br> | Biological: Senl-T7<br>* Patients will be treated with CD7 CAR-T cells<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence and severity of adverse events | To evaluate the possible adverse events occurred within first one month after CD7 CAR-T infusion, including the incidence and severity of symptoms such as cytokine release syndrome and neurotoxicity | First 1 month post CAR-T cells infusion | 
| Remission Rate | To obsere the efficacy of CAR-T cells after infusion, complete remission (CR), complete remission with incomplete recovery of blood cells (CRi), minimal tumor residual positive(MRD+) or negative (MRD-) CR/CRi, disease recurrence or progression (PD) will be used for evaluation. | 3 months post CAR-T cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| duration of response (DOR) | duration of response (DOR) | 24 months post CAR-T cells infusion | 
| CAR-T proliferation | the copy number of CD7 CAR- T cells in the genomes of PBMC by qPCR method | 3 months post CAR-T cells infusion | 
| progression-free survival (PFS) | progression-free survival (PFS) time | 24 months post CAR-T cells infusion | 
| Cytokine release | Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry | First 1 month post CAR-T cells infusion | 
| CAR-T proliferation | percentage of CD7 CAR- T cells measured by flow cytometry method | 3 months post CAR-T cells infusion |