Evaluate the Safety and Effect of ThisCART19A in Patients With AIDS Related B Cell Lymphoma/Lympholeukemia

Study Overview
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Brief Summary
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This is an open label, phase I study to assess the safety and efficacy of ThisCART19A in patients with AIDS related B cell lymphoma/lympholeukemia.

Official Title
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To Evaluate the Safety, Efficacy, Pharmacokinetics of ThisCART19A in Patients With AIDS Related B Cell Lymphoma/Lympholeukemia

Conditions
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AIDS Related Lymphoma and Lympholeukemia

Intervention / Treatment
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* Biological: ThisCART19A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65. Patients with AIDS-associated B-cell lymphoma/leukemia, including but not limited to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma tranferring to DLBCL, mantle cell lymphoma (MCL), follicular lymphoma 3B (FL-3B), original Mediastinal (thymus) large B-cell lymphoma, high-grade B-cell lymphoma and leukemia. At least received first line treatment. Had available evaluation lesion. ECOG(Eastern Cooperative Oncology Group) ≤ 1 or Karnofsky ≥ 60%. Had good organic function within 4 weeks before enrollment: Alanine aminotransferase(ALT)≤5×ULN(Upper limit of normal) and total bilirubin(TBIL)<2.0 mg/dL(for patients with Gilbert heald diseases, live involvement and taking atazanavir or indinavir, TBIL<3.0 mg/dL can be enrolled.); Left ventricular ejection fraction(LVEF)≥40%; Absolute neutrophile counts≥1000/mm3; thrombocyte≥30000/mm3; Serum creatinine≤1.5×ULN or creatinine clearance>30 mL/min/1.73 m2. Confirmed Cluster of differentiation(CD)19 positive by biopsy for the patients who received CD19 target therapy before. Confirmed Human immunodeficiency virus(HIV)-1 infection. HIV virus loading < 200 copy/ml within 4 weeks before screening. CD4+T cell counts >50 cells/mm3 within 4 weeks before screening. Patients with TBIL≤ 1.5 mg/dL, Aspartate aminotransferase(AST) and ALT ≤ 3×ULN, and hepatitis B virus(HBV) DNA <2000 IU/ml can be enrolled for HBV positive patients(defined as hepatitis B virus surface antigen(HBsAg) positive and hepatitis B core(HBc)-total positive ) and hepatitis C virus(HCV) positive patients(defined as HCV antibody positive) . Patients with cirrhosis are excluded. Hepatitis B core antibody(HBcAb) positive patients enrolled in this trial have to taking anti-HBV drugs during the whole research. Exclusion Criteria: Known for allergic to the preconditioning measures. Uncontrollable bacterial, fungal, viral infection before enrollment. Patients with pulmonary embolism within 3 months prior enrollment. Intolerable serious cardiovascular and cerebrovascular diseases and hereditary diseases. Imaging confirmed the presence of central nervous system involvement(including primary and secondary) and rapid progressing diseases. Receive allogeneic hematopoietic stem cell transplantation. Systemic steroid use (e.g., prednisone ≥20mg) within 3 days prior to screening. iIntermittent use of topical, inhaled or intranasal steroids recently or currently. Or systemic disease requiring long-term use of immunosuppression drugs. Excluded the patients received Influenza vaccinations within 2 weeks prior to lymphodepletion (Received Severe Acute Respiratory Syndrome-Corona virus disease(SARS-COV)19 vaccines could be included. Received inactivated, live/non-live adjuvant vaccines could be enrolled). Excluded women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after infusion. Male subjects planning pregnancy within 1 year after infusion should be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ThisCART19A 2×10^6 cells/kg for dose level 1<br>Patients will receive 2×10^6 cells/kg of ThisCART19A | Biological: ThisCART19A<br>* ThisCART19A is a new type CAR-T cells therapy for patients with lymphoma and lympholeukemia<br>|
| Experimental: ThisCART19A 3×10^6 cells/kg as dose level 2<br>Patients will receive 3×10^6 cells/kg of ThisCART19A | Biological: ThisCART19A<br>* ThisCART19A is a new type CAR-T cells therapy for patients with lymphoma and lympholeukemia<br>|
| Experimental: Patients will receive 4×10^6 cells/kg as dose level 3<br>Patients will receive 4×10^6 cells/kg of ThisCART19A | Biological: ThisCART19A<br>* ThisCART19A is a new type CAR-T cells therapy for patients with lymphoma and lympholeukemia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limited toxicity(DLT) observation and the incidence of treatment-emergent adverse events(TEAE) which more than or equal to grade 3 in each dose level | DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response rate in patients with AIDS related lymphoma | The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment | 12 months | 
| The change characteristics of chimeric antigen receptor(CAR)-T cell number and copy number in patients after infusion | Track CAR-T cells expansion in patients after infusion | 6 months | 
| Analysis the change characteristics of cytokines and immune effect cells number in patients after infusion | Analysis the effect cells and cytokines in patients after infusion | 3 months | 
| Analysis the severity and Incidence of Adverse Events in each dose level | Including more than or equal to grade 3 adverse events graded according to the NCI CTCAE v5.0, the adverse events with special consideration | 12 months | 
| Analysis the immunogenicity(Anti-therapeutic antibody and neutralizing antibody) of CAR-T cells in patients after infusion | Analysis the Anti-therapeutic antibody and neutralizing antibody level after infusion | 24 months |