Clinical Study on the Safety and Efficacy of CD7 CAR-T Cell in Patients With Relapsed/Refractory Acute Leukemia
Phase: PHASE1
Conditions: Acute-Leukemia
Sponsor: The General Hospital of Western Theater Command

 
 
Clinical study on the safety and efficacy of CD7 CAR-T cell in 
patients with relapsed/refractory acute leukemia 
 
 
 
 
 
 
2023．10．01 
 
 
 
 
 
 
 
 
 
 
 
 
 

Objective 
To evaluate the clinical safety and tolerability of CD7 CAR-T in the treatment of 
relapsed refractory acute leukemia 
Investigational 
drug 
CD7 CAR-T 
Planned 
number 
of 
cases 
200 
indication 
relapsed/refractory acute leukemia 
Research 
purpose 
Main purpose: 
➢ 
To evaluate the clinical safety and tolerability of CD7 CAR-T therapy. 
 
Secondary purpose: 
➢ 
Preliminary evaluation of the clinical efficacy of CD7 CAR-T therapy 
(according to clinical evaluation criteria) 
 
Exploratory purpose: 
➢ 
To explore the expansion and persistence of CD7 CAR-T in vivo and its 
correlation with clinical efficacy 
➢ 
To explore the correlation between pharmacodynamic (PD) biomarkers of 
CD7 CAR-T and clinical efficacy 
➢ 
To explore in vivo expansion and persistence of CD7 CAR-T and the 
association of pharmacodynamic (PD) biomarkers with cytokine release 
syndrome (CRS) and neurological events 
Research 
design 
This is an open, single-arm, single-center, prospective clinical study. 
Main contents of clinical research: 
To evaluate the clinical safety and tolerability of CD7 CAR-T in the treatment of 
relapsed refractory acute leukemia 
 
Dosage plan: 
It is planned to enroll 200 subjects for dose-limited toxicity (DLT) assessment, 
and the presence of non-evaluable subjects will increase the number of 
subjects, which will lead to an increase in the actual sample size. 

CD7 expression was determined by flow cytometry in 200 subjects. After the 
target was determined, the subjects received the target dose of CD7 CAR-T 
from 1×106 to 1×108 /kg. Each subject will start at a low dose of 1 x 106/kg and 
increase to the next dose if there are no significant side effects until the 
maximum tolerated dose is reached. 
If the incidence of DLT during the study is greater than 1/3, the SRC will discuss 
the conduct of the trial based on the safety profile of the subjects and the in 
vivo pharmacokinetics and pharmacodynamics data of CD7 CAR-T. 
CRS will be graded according to the revised grading System (Lee 2014). Crs-
related adverse events will be evaluated to determine whether they are DLT 
based on CRS overall grading. Consistent with non-CRS toxicity, all grade 3 CRS 
lasted >7 days and all grade 4 CRS were judged to be DLT, except as described 
above. 
Dlt-evaluable subjects: For accurate assessment of DLT, DLT-evaluable subjects 
were defined as receiving CD7 CAR-T infusion therapy. DLT non-evaluable 
subjects will be replaced and will result in an increase in the actual sample size. 
Drug Safety Monitoring Committee (SRC) During the trial, a Drug Safety 
Monitoring Committee (SRC) composed of principal investigators and 
laboratory members will be established to evaluate the safety data generated 
during the trial and jointly make recommendations for further trials. 
 
Evaluation of curative effect: 
• Remission criteria for acute leukemia will be applied to the NCCN guideline 
evaluation criteria until 24 months after CAR T cell infusion or disease 
progression, whichever occurs first, as specified in the Efficacy Evaluation 
Criteria. 
 
Security assessment: 
The study will collect adverse events (including neurological events, 
hematological events, infections, and secondary tumors) from the day after the 
CAR T cell infusion to 24 months after the infusion. 
Research 
treatment 
procedures 
Screening period: 
➢ 
flow cytometry: 5ml of bone marrow was collected by deep purple tube 
and sent for flow cytometry. The expression of CD7 was determined by 
flow cytometry. 

➢ 
The length of the screening period for eligible subjects depends on 
tumor burden at the time of enrollment, immunosuppressive drug use, 
and vital signs 
 
Treatment period: 
➢ 
Pretreatment chemotherapy: cyclophosphamide 500 mg/m2 and 
fludarabine 30 mg/m2 by intravenous infusion, all administered on days -
5, -4, and -3 
➢ 
CAR T cell input: Subjects were hospitalized to complete CD7 CAR T input 
and were required to be hospitalized for observation for at least 2 weeks 
after the input. 
 
Follow-up period: 
To CAR T cell infusion for two years 
Inclusion 
Criteria 
1. Patients diagnosed with acute leukemia. 
2. Acute leukemia complex/refractory cases with poor response to 
conventional chemotherapy: 1) patients who did not achieve complete 
remission after 2 courses of treatment with standard induced remission 
regimen; 2) Recurrence within 6 months after the first remission; 3) 
Relapse 6 months after the first remission, but failure to be treated again 
with the original induced remission regimen; 4) Recurrent patients. 
3. At least 2 weeks or 5 half-lives (whichever is shorter) from the start of 
preconditioning chemotherapy after prior systemic treatment, except for 
immune checkpoint inhibitors/agonists; Systemic immune checkpoint 
inhibitor/agonist treatment is at least 3 half-lives away from pre-
treatment chemotherapy (e.g., ipilimumab, etc.). 
4. Toxic reactions caused by previous antitumor therapy must be stabilized 
and returned to ≤ grade 1 (except for clinically insignificant toxicity, such 
as baldness). 
5. Over 14 years old, under 65 years old. 
6. Physical Strength score 0-3 (ECOG standard) 
7. No obvious active infection or graft-versus-host disease 
8. Expected survival ≥3 months 
9. Adequate kidney, liver, lung and heart function, defined as: 
Creatinine clearance (estimated by Cockcroft Gault formula) > 60 
mL/min; Serum ALT/AST ≤ 2.5 ULN; Total bilirubin ≤1.5 ULN, 
excluding subjects with Gilbert's syndrome; Cardiac ejection fraction 
≥ 50%, echocardiography confirmed centropericardial effusion, and 
ECG showed no clinically significant abnormal findings. 

There was no clinically significant pleural effusion. Baseline blood 
oxygen saturation under indoor ventilation was > 92%. 
10. The serum pregnancy test results of fertile women must be negative 
(women who have undergone surgical sterilization or at least 2 years 
after menopause are considered to be infertile). 
Exclusion 
Criteria 
1. The subject has had other malignancies, non-melanoma skin tumors, 
carcinoma in situ (e.g. Cervix, bladder, breast), unless disease-free 
survival of at least 3 years 
2. Presence or suspicion of uncontrollable fungal, bacterial, viral or other 
infections. 
3. Known human immunodeficiency virus (HIV) infection 
4. Known history of hepatitis B (HBsAg positive) or hepatitis C (HCV 
antibody positive). Subjects with latent or prehepatitis B infection 
(defined as HBcAb positive and HBsAg negative) can be enrolled only if 
PCR tests for HBV DNA are negative. In addition, these subjects were 
required to undergo a monthly PCR test for HBV DNA. Participants who 
are serologically positive for HCV antibodies can also be enrolled if their 
PCR test results for HCV RNA are negative. 
5. Existing or past CNS disease, such as seizures, cerebrovascular 
ischemia/bleeding, dementia, cerebellar disease, or any CNS-related 
autoimmune disease 
6. Subjects with severe heart disease, such as uncontrolled or symptomatic 
arrhythmias, congestive heart failure, or myocardial infarction within 6 
months prior to screening, or any grade 3 (moderate) or 4 (severe) heart 
disease (according to the New York Heart Society Functional Grading 
Method NYHA) with lymphoma infiltrating the heart's atria or ventricles 
7. A history of myocardial infarction, angioplasty or stent placement, 
unstable angina pectoris, or other clinically significant heart disease in 
the 12 months prior to enrollment 
8. Emergency treatment is expected or likely to occur within 6 weeks due to 
rapid tumor progression (e.g. tumor mass compression) 
9. Primary immune deficiency 
10. History of symptomatic deep vein thrombosis or pulmonary embolism 
within 6 months prior to enrollment 
11. Any medical condition that may affect the evaluation of safety or efficacy 
12. Have had severe rapid hypersensitivity reactions to any of the drugs to 
be used in this study 
13. Administer live vaccine within ≤6 weeks prior to initiation of the 
pretreatment regimen 
14. Pregnant or lactating female subjects 

15. Male or female subjects who do not consent to effective contraception 
from the time they sign informed consent until 6 months after 
completing AT19 treatment 
16. Subjects judged by the investigator had difficulty completing all visits or 
procedures required by the study protocol (including follow-up visits), or 
were not compliant enough to participate in the study 
17. In the past 2 years, subjects have had other malignancies, non-
melanoma skin tumors, carcinoma in situ (e.g. Cervix, bladder, breast), 
end-organ damage due to autoimmune diseases (e.g. Crohn's disease, 
rheumatoid arthritis, systemic lupus erythematosus), or need to 
systematically administer immunosuppressive or other drugs for 
systemic disease control. Unless disease free survival of at least 3 years 
18. Participate in other clinical experimenters during the same period 
Evaluation 
index of 
curative effect 
Remission criteria for acute leukemia 
• 
Complete Remission (CR) : 
➢ 
Bone marrow: primitive + naive cell count ≤ 5%, red blood cell and 
megakaryocyte line normal. 
➢ 
Hematography: hemoglobin (Hb) ≥100g /L (male) or ≥90g /L 
(female and children), neutrophil absolute value ≥ 1.5 ×10^9/L, 
platelet count ≥100×10^9/L, no leukemia cells in the classification. 
➢ 
Clinical manifestations: no symptoms and signs caused by leukemia 
infiltration, life is normal or nearly normal. 
• 
Partial response (PR) : The number of primitive + naive cells in the bone 
marrow is > 5%, ≤ 20%, or one of the clinical or hematologic two criteria 
does not meet the complete response criteria. 
• 
No response (NR) : Those who did not meet the above criteria in bone 
marrow, blood, or clinical Settings. 
 
leukemia recurrence 
• 
Relapse occurs in one of the following: 
• 
The number of primitive + naive cells in bone marrow was > 5%, ≤ 20%, 
and clinical remission could not be achieved after 1 course of anti-
leukemia therapy. 
• 
Bone marrow primitive + naive cell count > 20%. 
• 
Patients with infiltration of extramedullary leukemia cells. 
 
Complete response rate (CR) and partial response rate (PR) after 3 months 
of CD7 CAR-T reinfusion; 
Recurrence rate, progression-free survival (PFS) and overall survival (OS) 
after 1 to 5 years of CD7 CAR-T reinfusion; 
The amount and duration of CD7 CAR-T in vivo. 
 

Objective response rate (ORR) : defined as investigator-determined 
complete response rate (CR) and partial response rate (PR). All subjects 
who did not meet objective response criteria were considered to be in no 
response at the analysis deadline. 
Duration of response (DOR) : defined as the time from the subject's first 
response (CR or PR) to the subject's disease progression or death from 
any cause. Subjects who did not develop disease progression or death by 
the analysis deadline were excluded at the time of the last tumor 
evaluation. 
Progression-free survival (PFS) : defined as the time from initiation of CAR 
T cell infusion to disease progression or death from any cause. Subjects 
who did not develop disease progression or death by the analysis deadline 
were excluded at the time of the last tumor evaluation. 
Overall survival (OS) : defined as the time from initiation of immunization 
infusion until death from any cause. All subjects who did not die by the 
analysis deadline were deleted based on the last contact time. 
Statistical 
method 
Sample size determination: 
The sample size of this experiment was not determined based on assumptions. 
Approximately 200 subjects are planned to be recruited based on the 
occurrence of DLT. Subjects whose DLT is not evaluable will be replaced, which 
may result in more subjects being enrolled than expected. 
 
Statistical analysis: 
In general, continuous variables such as age will be described statistically using 
observations, mean, median, standard deviation, minimum, and maximum; 
Categorical variables are described statistically using the frequency of each 
category and its percentage. To the event occurrence time variable, Kaplan-
Meier method was used to summarize the data. If the data allows, calculate 
the median and quartile. The number of incidents and deletions will also be 
presented. 
The final analysis of the study will be based on data collected by the subjects 
throughout the study period. The efficacy evaluable analysis included all 
subjects treated with a dose of at least 1.0×106CAR T cells /kg who had 
baseline tumor evaluation and at least one post-baseline tumor evaluation. 
The safety analysis set included all subjects who received CAR T cell 
transfusions. The statistical methods will be detailed in the statistical analysis 
plan. 
 
Safety evaluation: 
Safety was evaluated by summary of adverse events, changes in laboratory 
results, and changes in vital signs. All subjects receiving CD7 CAR-T infusion will 

be included in the safety analysis (i.e., the safety analysis set). 
Adverse events will be graded according to NCI CTCAE (version 4.03). Adverse 
events were coded using the International Dictionary of Medical Terms 
(MedDRA). Summarize the number and frequency of adverse events according 
to the classification of human organ systems with appropriate terms. All SAEs 
(including death), DLT, AESI need a separate list summary. 
Changes in laboratory results will be summarized according to NCI CTCAE 
(version 4.03) grading. For laboratory indicators, the highest level of toxicity 
that occurred during the test was summarized in the form of counts and 
percentages. Changes in vital signs and physical strength scores were 
compared to baseline levels for descriptive statistics. Some vital signs and 
laboratory test results will be graphically summarized for each subject's data 
over time. 
 
Curative effect evaluation: 
Descriptive statistical methods were used in this study, including 
complete response rate, partial response rate, objective response rate, 
progression-free survival, overall survival, recurrence rate, and CD7 CAR-T 
retention and duration in vivo. All adverse events (including serious adverse 
events) are described and their incidence is calculated with a 95% confidence 
interval. Survival information was analyzed using Kaplan-Meier curves.