Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With Refractory or Relapsed B Cell Lymphoma

Trial Title: Safety, Efficacy and Pharmacokinetics of ThisCART19A in Patients With Refractory or Relapsed B Cell Lymphoma

NCT ID: NCT05776407

Condition: Refractory or Relapsed B Cell Lymphoma

Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Cyclophosphamide
Fludarabine
Etoposide

Conditions: Keywords:
Allogeneic CAR T，B cell Lymphoma

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: ThisCART19A
Description: Single dose of Allogeneic Anti-CD19 CAR T cells (ThisCART19A) will be infused after the lymphodepletion conditioning of Fludarabine, Cyclophosphamide and Etoposide.
Arm group label: ThisCART19A cells infusion

Other name: Allogeneic Anti-CD19 CAR T cells

Intervention type: Drug
Intervention name: Fludarabine
Description: Fludarabine is used for lymphodepletion.
Arm group label: ThisCART19A cells infusion

Intervention type: Drug
Intervention name: Cyclophosphamide
Description: Cyclophosphamide is used for lymphodepletion.
Arm group label: ThisCART19A cells infusion

Intervention type: Drug
Intervention name: Etoposide
Description: Etoposide is used for lymphodepletion.
Arm group label: ThisCART19A cells infusion

Other name: VP-16

Summary: This is a phase 1/2, open-label study to assess the efficacy, safety and pharmacokinetics of ThisCART19A (Allogeneic Anti CD19 CAR-T) in patients with refractory or relapsed CD19 positive B cell Lymphoma.

Detailed description: This is a phase 1/2, single-center, nonrandomized, open-label, dose-escalation and dose-expansion study to evaluate the efficacy, safety and pharmacokinetics of ThisCART19A in patients with r/r CD19 positive B cell Lymphoma and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile. AIDS-related B-cell lymphoma were not excluded from this clinical trial. Before initiating ThisCART19A infusion, subjects will be administered lymphodepletion chemotherapy composed of fludarabine、cyclophosphamide and VP-16. At Day 0 of the Treatment Period, subjects will receive an intravenous (IV) infusion of ThisCART19A. All subjects are monitored during the treatment period through Day 42. All subjects who receive a dose of ThisCART19A will be followed up to 2 years.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. 18 years ≤ age ≤ 65 years. 2. Voluntarily sign a documented IRB-approved ICF prior to any screening procedure. 3. Patients with histologically confirmed B-cell NHL defined by the World Health Organization (WHO) 2016, including but not limited to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma transferring to DLBCL, mantle cell lymphoma (MCL), follicular lymphoma 3B (FL-3B), original Mediastinal (thymus) large B-cell lymphoma, high-grade B-cell lymphoma and AIDS-associated B-cell lymphoma. 4. Prior therapy must have included: Anti-CD20 monoclonal antibody and Anthracycline containing chemotherapy regimen. 5. Had available evaluation lesion. 6. ECOG(Eastern Cooperative Oncology Group) ≤ 2 or Karnofsky ≥ 60%. 7. Serum creatinine≤1.5×ULN or creatinine clearance>30 mL/min/1.73 m2. 8. 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.) 9. Left ventricular ejection fraction(LVEF)≥40% 10. Absolute neutrophile counts≥1000/mm3 11. Thrombocyte≥30000/mm3 12. Total bilirubin(TBIL) ≤ 2.0 mg/dL 13. Confirmed Cluster of differentiation(CD)19 positive by biopsy for the patients who received CD19 target therapy before. 14. Pregnancy tests for women of childbearing age shall be negative; Both men and women agreed to use effective contraception during treatment and during the subsequent 1 year. 15. AIDS Related B Cell Lymphoma :HIV virus loading < 200 copy/ml and CD4+T cell counts >200 cells/mm3 within 4 weeks before screening. 16. 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. 17. Hepatitis B core antibody(HBcAb) positive patients enrolled in this trial have to taking anti-HBV drugs during the whole research. Exclusion Criteria: 1. Known for allergic to the preconditioning measures. 2. Uncontrollable bacterial, fungal, viral infection before enrollment. 3. Patients with pulmonary embolism within 3 months prior enrollment. 4. Intolerable serious cardiovascular and cerebrovascular diseases and hereditary diseases. 5. Imaging confirmed the presence of central nervous system involvement(including primary and secondary) and rapid progressing diseases. 6. Receive allogeneic hematopoietic stem cell transplantation less than 100 days. 7. 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. 8. 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). 9. 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.

Gender: All

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: No

Locations:

Facility:
Name: Chongqing University Cancer Hospital

Address:
City: Chongqing
Zip: 400030
Country: China

Start date: May 2023

Completion date: November 2024

Lead sponsor:
Agency: Chongqing University Cancer Hospital
Agency class: Other

Collaborator:
Agency: Fundamenta Therapeutics, Ltd.
Agency class: Industry

Source: Chongqing University Cancer Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05776407