Leukemia, T Cell
Conditions
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 CD7 Positive acute leukemia or mixed lineage leukemia except those who are diagnosed with T-ALL/T-LBL
Detailed description
The CARs consist of an anti-CD7 VHHs, 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 CD7 Positive acute leukemia or mixed lineage leukemia except those who are diagnosed with T-ALL/T-LBL The Secondary research objectives: To investigate the cytokinetic characteristics of CD7 CAR-T cells in patients with CD7 Positive acute leukemia or mixed lineage leukemia except those who are diagnosed with T-ALL/T-LBL
Interventions
BIOLOGICALCD7 CART
Biological: CD7 CAR-T; Drug: Cyclophosphamide,Fludarabine; Procedure: Leukapheresis
Sponsors
Hebei Senlang Biotechnology Inc., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of refractory or relapsed CD7+ acute myeloid leukemia or mixed lineage leukemia was made according to the NCCN 2019.V2 guideline. Refractory AML is defined as a patient who has failed to achieve complete remission after induction therapy. Relapsed AML is defined as the reappearance of blasts (5%) in either peripheral blood or bone marrow. Patient diagnosed with AML should be treated and whose disease failed with at least 2 prior lines of therapies. 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; 2. CD7+ expression on tumor cells (CD7 positive blasts ≥50% by flow cytometry); 3. Life expectancy greater than 12 weeks; 4. KPS or Lansky score≥60; 5. HGB≥70g/L (can be transfused); 6. oxygen saturation of blood\>90%; 7. Total bilirubin (TBil)≤3 × upper limit normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal; 8. Informed consent explained to, understood by and signed by patient/guardian
Exclusion criteria
1. 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); 2. Has an active GvHD; 3. Has a history of severe pulmonary function damaging; 4. With other tumors which is/are in advanced malignant and has/have systemic metastasis; 5. Severe or persistent infection that cannot be effectively controlled； 6. Merging severe autoimmune diseases or immunodeficiency disease; 7. Patients with active hepatitis B or hepatitis C(\[HBVDNA+\]or \[HCVRNA+\]); 8. Patients with HIV infection or syphilis infection; 9. Has a history of serious allergies on Biological products (including antibiotics); 10. Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6; 11. 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.; 12. Have received transplant treatment for less than 6 months in prior to enrollment; 13. Being pregnant and lactating or having pregnancy within 12 months; 14. Any situations that the researchers believe will increase the risks for the subject or affect the results of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Incidence and severity of adverse events | First 1 month post CAR-T cells infusion | 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 |
| Efficacy: Remission Rate | 3 months post CAR-T cells infusion | In the presence of extramedullary lesions, complete remission (CR), partial remission (PR), stable disease (SD), disease recurrence or progression (PD) shall be used to describe extramedullary lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CAR-T proliferation | 3 months post CAR-T cells infusion | the copy number of CD7 CAR- T cells in the genomes of PBMC by qPCR method |
| Cytokine release | First 1 month post CAR-T cells infusion | Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry method |
| duration of response (DOR) | 24 months post CAR-T cells infusion | duration of response (DOR) |
| Pharmacodynamic (PD) indicators | First 1 month post CAR-T cells infusion | the pharmacodynamic change in the clearance of peripheral blood CD7+ cells and the release of the cytokines at each observation time point |
| Pharmacokinetics (PK) indicators | 24 months post CAR-T cells infusion | 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 |
| Efficacy: progression-free survival (PFS) | 24 months post CAR-T cells infusion | progression-free survival (PFS) time |
Countries
China
Outcome results
None listed