Phase Ⅰ Clinical Study of Anti-CD52 Monoclonal Antibody in NHL and T-PLL

Inclusion Criteria: For Patients With Relapsed And Refractory Chronic Lymphocytic Leukemia/Small LymphocyticLymphoma/Lymphoblastic Leukemia (CLL/SLL/PLL) And Initial Treated t-Lymphoblastic Leukemia ( InitialTreated T-PLL)

-Patients with CLL/SLL or PLL were confirmed by histopathological or flow immunotyping;

1. Patients with indications for treatment according to iwCLL2018 criteria and determinedby the investigator;
2. Age from 18 to 70 (including boundary value), no gender limitation;
3. ECOG physical condition score 0 ~ 2;
4. Patients have measurable lesions (lymphadenopathy (maximum baseline diameter ≥1.5 cm),or hepatomegaly/splenomegaly due to CLL or PLL or peripheral tumor lymphocytes >5×10E9/L);
5. CLL/SLL patients are intolerant or resistant to previous BTK inhibitor treatment; Ornewly treated patients with T-PLL; Or relapse-resistant PLL (relapse-resistant PLL isdefined as disease progression following recent remission of treatment.Treatment-resistant disease was defined as failure to achieve ≥PR from the most recenttreatment or disease progression within 6 months of the last treatment);
6. Laboratory test results must meet the following requirements (no blood components,short-acting cell growth factor and other drugs are allowed within 7 days prior tolaboratory test; Long-acting growth factor is not allowed within the first 14 days),and laboratory test results within 7 days before screening;

• Bone marrow function: Neutrophils ≥1×10E9/L, platelets ≥50×10E9/L, and hemoglobin ≥75g/L were observed without growth factor support treatment.
• Liver function: AST and ALT ≤2×ULN (no liver invasion); Alanine aminotransferaseor/and aspartate aminotransferase ≤5×ULN (liver aggressor). Total bilirubin ≤2×ULN;
• Renal function: serum creatinine ≤2×ULN and creatinine clearance rate > 50mL/min;
• Blood coagulation function: international standardized ratio (INR) ≤1.5×ULN andactivated partial thrombin time (APTT) ≤1.5×ULN;

7. Life expectancy > 3 months;
8. Fertile men and women of reproductive age are willing to take effective contraceptivemeasures from the signing of informed consent to 6 months after the lastadministration of the experimental drug; Women of childbearing age must have anegative blood pregnancy test no later than 7 days before the first trial drug isadministered.
9. Agreed to follow the experimental treatment plan and visit plan, voluntarily enrolledin the study, and signed written informed consent. For Other Relapsed And Refractory Non-Hodgkin's Lymphoma
10. Non-hodgkin's lymphoma was confirmed by histopathology according to world HealthOrganization (WHO) classification of disease, and did not respond to standardtreatment;
11. ECOG physical condition score 0~2;
12. Age from 18 to 70 (including boundary value), no gender limitation;
13. Life expectancy > 3 months;
14. At least one measurable lesion with a maximum diameter ≥1.5cm is present;
15. Laboratory test results must meet the following requirements (no blood components,short acting cell growth factor, albumin and other drugs are allowed to be givenwithin 7 days before obtaining laboratory test; Long acting growth factor is notallowed in the first 14 days) :

• Bone marrow function: Neutrophils ≥1×10E9/L, platelets ≥50×10E9/L, and hemoglobin ≥75g/L were observed without growth factor support treatment.
• Liver function: AST and ALT ≤2×ULN (no liver invasion); Alanine aminotransferaseor/and aspartate aminotransferase ≤5×ULN (liver aggressor). Total bilirubin ≤2×ULN;
• Renal function: serum creatinine ≤2×ULN and creatinine clearance rate >50mL/min;
• Blood coagulation function: international standardized ratio (INR) ≤1.5×ULN andactivated partial thrombin time (APTT) ≤1.5×ULN;

7. Agreed to follow the experimental treatment plan and visit plan, voluntarily enrolledin the study, and signed written informed consent.

Exclusion Criteria:

• For Patients With Relapsed And Refractory CLL/SLL/PLL And Initial Treated T-PLL

1. Central nervous system (CNS) or meningeal involvement or history of suchinvolvement before enrollment;
2. Received systemic steroid hormone (dose equivalent to prednisone ≥10mg/ day) andantitumor therapy within 7 days prior to initial administration of the studydrug, chemotherapy, targeted therapy, radiotherapy or antibody therapy within 4weeks or 5 half-lives, whichever is older; Failure to recover from AE associatedwith prior systemic antitumor therapy to nCI General Adverse Event Term version 5.0 (CT CAE Version 5.0) grade ≤1 (except hair loss);
3. Those who had undergone major surgery, severe trauma or were expected to undergomajor surgery during the study period within 4 weeks prior to the firstadministration of the study drug and were judged by the investigator to beunsuitable for inclusion;
4. Autoimmune cytopenia with clinical manifestations;
5. Have a history of active, known autoimmune deficiency, or other acquired,congenital immune deficiency diseases, or a history of organ transplantation;
6. There was a history of other active malignant tumors within 2 years prior to theentry of the study, except for the following cases :(1) effectively controlledcervical cancer in situ; (2) effectively controlled local basal cell carcinoma ofskin; (3) Other previous malignant tumors that have been clinically cured andhave no clinical signs for ≥5 years;
7. Currently has clinical significance of cardiovascular disease, activity, such asuncontrolled arrhythmias, uncontrolled hypertension, congestive heart failure,according to the New York heart association functional class determine any 3 or 4heart disease, or a period of 6 months before screening history of myocardialinfarction, or heart left ventricular ejection fraction < 50%;
8. Had active systemic infections (bacterial, fungal, viral, etc.) within 2 weeksprior to enrollment, including infections being treated with oral or intravenousantibiotics;
9. Known patients with acute or chronic active hepatitis b (HBsAg positive and HBVDNA viral load ≥200IU/mL or ≥10E3 copy number /mL, other abnormal results will bedetermined by the investigator whether to add quantitative HBV DNA test orexclude); Acute or active hepatitis C (HCV antibody positive); And otheracquired, congenital immunodeficiency diseases, including but not limited toHIV-infected persons; Or treponema pallidum antibody positive; Or CMV-DNApositive;
10. Patients with or clinically suspected Richter's syndrome at the time ofscreening;
11. Patients who received or received radiation therapy within the first 4 weeks ofenrollment (except for treated bone marrow volume less than 10% and patients withevaluable lesions beyond the radiation report). Prior radioimmunotherapy within 3months prior to initiation of the study drug;
12. Are currently participating in an interventional clinical trial treatment, orhave been treated with another clinical trial drug or device within 4 weeks priorto initial administration;
13. Received any live virus vaccine or attenuated live vaccine within 3 months priorto enrollment;
14. Prior allogeneic stem cell transplantation or autologous hematopoietic stem celltransplantation or any active graft-versus-host disease basis orimmunosuppressant use within 21 days prior to initiation of investigationaltherapy;
15. Known history of allergic diseases or severe allergies; Or is known to beallergic to protein preparations, biological agents, or any component of the testdrug;
16. Those who have a history of drug abuse or drug abuse after inquiry;
17. Pregnant or lactating women;
18. The investigator considered that the patient had other conditions that mightaffect compliance or ineligibility for the study.

• For Other Relapsed And Refractory Non-Hodgkin's Lymphoma

1. Highly aggressive lymphoma of indolent lymphoma transformation;
2. Known patients with acute or chronic active hepatitis b (HBsAg positive and HBVDNA viral load ≥200IU/mL or ≥10E3 copy number /mL, other abnormal results will bedetermined by the investigator whether to add quantitative HBV DNA test orexclude); Acute or active hepatitis C (HCV antibody positive); And otheracquired, congenital immunodeficiency diseases, including but not limited tohiv-infected persons; Or treponema pallidum antibody positive; Or cmV-DNApositive;
3. Received any anti-tumor therapy (including radiotherapy, chemotherapy, hormonetherapy [dose equivalent to prednisone ≥10mg/ day], surgery or targeted therapy,immunotherapy, etc.) within 4 weeks or 5 half-life periods (whichever is longer)prior to the start of the study drug; Recovery from AE associated with priorsystemic antitumor therapy to NCI General Adverse Event Term version 5.0 (CT CAEVersion 5.0) grade ≤1 (except hair loss);
4. Clinically significant heart disease, including unstable angina, acute myocardialinfarction 6 months prior to randomization, congestive heart failure (NYHA) heartfunction grade III or IV; Or left ventricular ejection fraction < 50%;
5. Lymphoma patients with central nervous system (CNS) invasion before enrollment;
6. Known history of prior drug allergy; Or is known to be allergic to proteinpreparations, biological agents, or any component of the test drug;
7. Those who had undergone major surgery or severe trauma within 4 weeks prior totreatment and were judged by the investigator to be unfit for inclusion;
8. Had received autologous or allogeneic hematopoietic stem cell transplantationbefore enrollment;
9. There was a history of other active malignant tumors within 2 years beforeentering the study, except for the following cases :(1) effectively controlledcervical cancer in situ; (2) effectively controlled local basal cell carcinoma ofskin; (3) Other malignant tumors that have been clinically cured and have noclinical signs for ≥5 years;
10. Had an active systemic infection (bacterial, fungal, viral, etc.) within 2 weeksprior to enrollment, including an infection being treated with oral orintravenous antibiotics;
11. Participants in other clinical trials within 4 weeks prior to enrollment;
12. Received any live virus vaccine or attenuated live vaccine within 3 months priorto enrollment;
13. Autoimmune cytopenia with clinical manifestations;
14. A history of drug abuse or drug abuse upon inquiry;
15. Pregnant or lactating women;
16. The investigator considered that the patient had other conditions that mightaffect compliance or ineligibility for the study.