a Clinical Research of CD19 and CD22 Targeted Prime CAR-T Cell in Relapsed/Refractory B Cell Lymphoma

Although the anti-CD19 CAR-T cell therapies have gained significant results in patients with relapsed and refractory B-cell hematologic malignancies.

There are patients who resisted anti-CD19 CAR-T cells or with CD19 negative relapse. To make further improvement, the investigators launch such a clinical trial using CD19 and CD22 targeted prime CAR-T cells for patients with relapsed and refractory B Cell Lymphomato evaluate the efficacy and safety of CD19 and CD22 targeted prime CAR-T cell therapy.

• CD19 and CD22 targeted prime CAR- T cells (Biological): A single infusion of CD19 and CD22 prime CAR-T cells will be administered intravenously

Primary outcomes

• Adverse events that related to treatment [2 years]: Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)
• The response rate of CD19 and CD22 prime CAR-T treatment in patients with relapse/refractory B Cell Lymphoma [6 months]: The response rate of CD19 and CD22 prime CAR-T treatment will be recorded and assessed according to the National Comprehensive Cancer Network Guideline

Secondary outcomes

• Rate of prime CAR-T cells in bone marrow [2 years]: Determine the rate of prime CAR-T cells in bone marrow by means of flow cytometry
• Rate of prime CAR-T cells in peripheral blood [2 years]: Determine the rate of prime CAR-T cells in peripheral blood by means of flow cytometry
• Quantity of prime CAR copies in bone marrow [2 years]: Determine the quantity of prime CAR copies in bone marrow by qPCR
• Quantity of prime CAR copies in peripheral blood [2 years]: Determine the quantity of prime CAR copies in peripheral blood by qPCR
• Rate of CD19 and CD22 positive cells in Bone marrow [1 years]: Determine the rate of CD19 and CD22 positive cells in bone marrow by flow cytometry
• Levels of IL-6 in Serum [3 months]: Serological determination of IL-6
• Levels of IL-10 in Serum [3 months]: Serological determination of IL-10
• Levels of TNF-α in Serum [3 months]: Serological determination of TNF-α
• Levels of CRP in Serum [3 months]: Serological determination of CRP
• Duration of Response (DOR) of CD19 and CD22 prime CAR-T treatment in patients with refractory/relapsed B Cell Lymphoma [2 years]: DOR will be assessed from the first assessment of CR/CRi to the first assessment of recurrence or progression of the disease or death from any cause (censored)
• Progress-free survival(PFS) of CD19 and CD22 targeted prime CAR-T treatment in patients with refractory/relapsed B Cell Lymphoma [2 years]: PFS will be assessed from the first prime CAR-T cell infusion to death from any cause or the first assessment of progression (censored)
• Overall survival(OS) of CD19 and CD22 prime CAR-T treatment in patients with refractory/relapsed B Cell Lymphoma [2 years]: OS will be assessed from the first primeCAR-T cell infusion to death from any cause (censored)

Sex: All, ages: 2 Years to 75 Years

Inclusion Criteria:

1. Signed written informed consent
2. Diagnose as Relapsed and Refractory B -ALL, and meet one of the following conditions:

   1. Failed to standard chemotherapy regimens;
   2. Relapse after complete remission, high-risk and / or refractory patients ;
   3. Relapse after hematopoietic stem cell transplantation;
3. Evidence for cell membrane CD19 or CD22 expression
4. All genders ages: 2 to 75 years
5. The expect time of survive is above 3 months;
6. KPS>60
7. No serious mental disorders ;
8. Left ventricular ejection fraction ≥50%
9. Sufficient hepatic function defined by ALT/AST≤3 x ULN and bilirubin≤2 x ULN;
10. Sufficient renal function defined by creatinine clearance≤2 x ULN;
11. Sufficient pulmonary function defined by indoor oxygen saturation≥92%;
12. With single or venous blood collection standards, and no other cell collection contraindications;
13. Ability and willingness to adhere to the study visit schedule and all protocol requirements.

Exclusion Criteria:

1. Previous history of other malignancy;
2. Presence of uncontrolled active infection;
3. Evidence of disorder that need the treatment by glucocorticoids;
4. Active or chronic GVHD
5. The patients treatment by inhibitor of T cell
6. Pregnant or breasting-feeding women;
7. Any situation that investigators regard not suitable for attending in this study (e.g. HIV , HCVinfection or intravenous drug addiction) or may affect the data analysis.

• Sanbin Wang, MD, Principal investigator, 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
• Cheng Qian, PhD, Principal investigator, Chongqing University Cancer Hospital