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

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

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.