AIDS Related Lymphoma and Lympholeukemia
Conditions
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.
Interventions
BIOLOGICALThisCART19A
ThisCART19A is a new type CAR-T cells therapy for patients with lymphoma and lympholeukemia
Sponsors
He Huang
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 28 days | DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Analysis the severity and Incidence of Adverse Events in each dose level | 12 months | Including more than or equal to grade 3 adverse events graded according to the NCI CTCAE v5.0, the adverse events with special consideration |
| Analysis the immunogenicity(Anti-therapeutic antibody and neutralizing antibody) of CAR-T cells in patients after infusion | 24 months | Analysis the Anti-therapeutic antibody and neutralizing antibody level after infusion |
| Objective Response rate in patients with AIDS related lymphoma | 12 months | The incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment |
| The change characteristics of chimeric antigen receptor(CAR)-T cell number and copy number in patients after infusion | 6 months | Track CAR-T cells expansion in patients after infusion |
| Analysis the change characteristics of cytokines and immune effect cells number in patients after infusion | 3 months | Analysis the effect cells and cytokines in patients after infusion |
Countries
China
Contacts
Primary ContactMing Ming Zhang, Doctor
Outcome results
None listed