Clinical trial NCT05340829: Evaluate the Safety and Effect of ThisCART19A in Patients With AIDS Related B Cell Lymphoma/Lympholeukemia
Official title: To Evaluate the Safety, Efficacy, Pharmacokinetics of ThisCART19A in Patients With AIDS Related B Cell Lymphoma/Lympholeukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: AIDS Related Lymphoma and Lympholeukemia
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2022-04-22
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 28 days
Secondary outcomes:
measure: Objective Response rate in patients with AIDS related lymphoma
timeFrame: 12 months
measure: The change characteristics of chimeric antigen receptor(CAR)-T cell number and copy number in patients after infusion
timeFrame: 6 months
measure: Analysis the change characteristics of cytokines and immune effect cells number in patients after infusion
timeFrame: 3 months
measure: Analysis the severity and Incidence of Adverse Events in each dose level
timeFrame: 12 months
measure: Analysis the immunogenicity(Anti-therapeutic antibody and neutralizing antibody) of CAR-T cells in patients after infusion
timeFrame: 24 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: First hospital affiliated Zhejiang University
name: He Huang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: