Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells

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

Detailed Description
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The CARs consist of an anti-CD7 single-chain variable fragment（scFv）, a portion of the human CD137（4-1BB） molecule, and the intracellular component of the human CD3ζ molecule. Prior to CAR-T cell infusion, the patients will be subjected to preconditioning treatment. After CAR-T cell infusion, the patients will be evaluated for adverse reactions and efficacy. The Main research objectives: To evaluate the safety and efficacy of CD7 CAR-T cells in patients with relapsed or refractory T-ALL/LBL The Secondary research objectives: To investigate the cytokinetic characteristics of CD7 CAR-T cells in patients with relapsed or refractory T-ALL/LBL

Official Title
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Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells

Conditions
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T-cell Acute Lymphoblastic Leukemia/Lymphoma

Intervention / Treatment
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* Biological: CD7 CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) according to the NCCN 2019.V2 Guideline. Refractory T-ALL is defined as a patient who has failed to achieve complete remission after induction therapy. Relapsed T-ALL is defined as the reappearance of blasts (5%) in either peripheral blood or bone marrow. Patients whose tumor burden >5% blasts, or who have persistent positive minimal residual disease (MRD), or have reappearance of extramedullary lesions are also considered eligible. CD7-positive tumor (≥70% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory). tumors burden >5%,or MRD+， or new extramedullary lesions reappeared. Life expectancy greater than 12 weeks KPS or Lansky score≥60 HGB≥70g/L 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； Presence of 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 to biological products (including antibiotics); Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6. Presence of any symtomatic CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement; Received allogeneic hematopoietic stem cell transplantation within 6 months; 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
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Minimum Age: 2 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 |
| --- | --- |
| Experimental: CD7 CAR-T<br>Patients will be treated with CD7 CAR-T cells | Biological: CD7 CAR-T<br>* Patients will be treated with CD7 CAR-T cells Biological: CD7 CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis;<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Incidence and severity of adverse events | To evaluate the possible adverse events occurred within the 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 | 
| Efficacy: Remission Rate | Remission Rate including complete remission(CR)、CR with incomplete blood count recovery(CRi)、partial remission(PR), No remission(NR), overall remission (OR) | 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 | 
| Efficacy: progression-free survival (PFS) | progression-free survival (PFS) time | 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 | 
| CAR-T proliferation | percentage of CD7 CAR- T cells measured by flow cytometry method | 3 months post CAR-T cells infusion | 
| Cytokine release | Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method | First 1 month post CAR-T cells infusion | 
| Pharmacokinetics (PK) indicators: | the peak concentration of Senl-T7 CAR-T cells amplified in the peripheral blood (Cmax, detected by flow cytometry and qPCR); the time taken to reach the peak concentration (Tmax), and the persistent time of the Senl-T7 CAR-T cells in vivo in patients; | Long time | 
| Pharmacodynamic (PD) indicators: | the pharmacodynamic change in the clearance of peripheral blood CD7+ cells and the release of the cytokines at each observation time point | First 1 month post CAR-T cells infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T-ALL，T-LBL , CD7，CAR-T