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

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

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.

Study Overview

• Status: Recruiting
• Conditions: AIDS Related Lymphoma and Lympholeukemia
• Intervention / Treatment: Biological: ThisCART19A

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ming Ming Zhang, Doctor; Phone Number: 13656674208; Email: mingmingzhang@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university
      • Contact: He Huang, Doctor; Phone Number: 86-13605714822; Email: hehuangyu@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: He Huang
• Investigators: Principal Investigator: He Huang, Doctor, First hospital affiliated Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2022
• Primary Completion (Anticipated): March 30, 2024
• Study Completion (Anticipated): April 30, 2024

Study Registration Dates

• First Submitted: April 9, 2022
• First Submitted That Met QC Criteria: April 17, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2022
• Last Update Submitted That Met QC Criteria: April 17, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, AIDS-Related
• Other Study ID Numbers: FT400-006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No