CAR2219 CAR-T Cells for the Treatment of R/R B Cell Leukemia and Lymphoma

Official title

Safety and Efficacy of CAR2219 CAR-T Cells in Treatment of Relapsed/refractory CD19/CD22 Positive B Cell Leukemia and Lymphoma

Overview

This is a single arm study to evaluate the safety and efficacy of CAR2219 CAR-T cells in the treatment of relapsed/refractory CD19/CD22 positive B cell Leukemia and Lymphoma.

Detailed description

This study is an exploratory clinical trial of a single-arm, open, single-center treatment of CAR2219 CAR-T cell. 20 subjects with relapsed or refractory CD19/ CD22 positive B-cell Leukemia and Lymphoma will be enrolled and received CAR2219 CAR T cells injection therapy, and related data such as adverse reactions and therapeutic effects after medication were followed up. To evaluate its safety and efficacy.

Interventions

• Genetic CAR2219-T cells
  Genetic: CAR2219-T cells Each subject will be infused with single dose of CD2219-CAR-T cells. A classic "3+3" dose escalation will be employed. The low dose is 5×10\^5 /kg, the medium dose is 1×10\^6 /kg, and the high dose is 2×10\^6 /kg. Drug: Fludarabine Fludarabine will be given at a dose of 30 mg/m2/day intravenously (IV) for 3 days prior to the infusion of CD2219-CAR-T cells. Drug: Cyclophosphamide Cyclophosphamide will be given at a dose of 300 mg/m2/day intravenously (IV) for 3 days pri

Primary outcome measures

• According to the incidence of treatment-related adverse events (AEs) to evaluate the safetyof CAR2219 CAR-T cells in the treatment of relapsed/refractory CD19+CD22+ B-cell Leukemia and Lymphoma. [Time frame: up to 2 years]
• According to the determine the Maximal Tolerable Dose(MTD) to evaluate the safetyof CAR2219 CAR-T cells in the treatment of relapsed/refractory CD19+CD22+ B-cell Leukemia and Lymphoma. [Time frame: MTD will be determined based on DLTs observed during the first 28 days of study treatment.]

Secondary outcome measures (1)

• According to the objective response rate (ORR) to evaluate the efficacy of CAR2219 CAR-T cells in the treatment of relapsed/refractory CD19+CD22+ B-cell Leukemia and Lymphoma. [Time frame: Within 3 months following infusion of CAR2219 CAR-T cells]

Eligibility criteria

Inclusion criteria

• Signed written informed consent;
• Relapsed/refractory CD19/CD22 positive B cell Leukemia or Lymphoma must be assured and meet one of the following conditions: (1) Confirmation for either CD19 or CD22 positivity using immunohistochemistry or flow cytometry; (2) B-cell tumors include the following three categories: ① B-cell acute lymphoblastic leukemia (B-ALL); Indolent B-cell lymphoma (CLL, FL, MZL, LPL, HCL); Aggressive B-cell lymphoma (DLBCL, BL, MCL) (3) Refractory/recurrent B-ALL (include one of the following situations) : ① relapse within 12 months after the first remission; ② The first refractory patients who did not achieve complete remission after 2 cycles of standard chemotherapy regimen; ③ Failure to achieve complete remission or relapse after first-line or multi-line salvage chemotherapy; ④ Recurrence after hematopoietic stem cell transplantation. (4) Refractory/recurrent B-cell lymphoma (meeting the requirements of 1 of the first 4 below plus 5) : ① After 4 courses of chemotherapy prescribed by the standard protocol, the tumor has shrunk by less than 50% or the disease progression(PD); ② CR reached after standard chemotherapy, but relapse occurred within 12 months; ③ Two or more recurrence after CR; ④ Recurrence after hematopoietic stem cell transplantation; ⑤Patients must have received rituximab or another anti-CD20 monoclonal antibody (unless Investigator determines that tumor is CD20-negative) and an anthracycline-containing chemotherapy regimen.
• All genders, ages: 14 to 75 years
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2.
• Life expectancy ≥3 months;
• HGB≥70g/L
• Liver,kidney function and cardiopulmonary function meet the following requirements: (1) creatinine ≤1.5×ULN; (2) left ventricular ejection fraction≥50%; (3) Oxygen saturation >90%; (4) Total bilirubin ≤1.5×ULN, ALT and AST≤2.5×ULN;
• Participants agreed to use contraception from the time of informed consent until 1 year after CAR-T cell infusion."

Exclusion criteria

• Severe heart failure with left ventricular ejection fraction <50%;
• A history of severe lung function impairment;
• Combined with other advanced malignant tumors;
• Complicated with severe infection that could not be effectively controlled;
• Severe autoimmune disease or congenital immune deficiency;
• Active hepatitis (hepatitis B virus DNA \[HBV-DNA\] or hepatitis C virus RNA \[HCV-RNA\] test results above the lower limit of detection);
• Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), or syphilis infection;
• History of severe allergy to biological products (including antibiotics);
• Allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients with acute graft-versus-host reaction (GVHD) one month after immunosuppressant withdrawal;
• Patients with other serious physical or mental illnesses or laboratory abnormalities that could increase the risk of participating in the study or interfere with the results of the study, and those who were deemed by the investigator to be unsuitable for participation in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• the Fifth Medical Center of Chinese People's Liberation Army General Hospital — Beijing

Identifiers

NCT: NCT06834529 · CAR2219-XYBYXB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗