Study of Sequential CAR-T Cell Treating Leukemia Children

NCT ID: NCT04340154

Last Updated: 2024-12-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 81 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-01
• Study Completion Date: 2024-11-30

Brief Summary

The investigators will conduct a phase II clinical trial of sequential chimeric antigen receptor T cell targeting at different B-cell antigens in refractory or relapsed B-cell acute lymphoblastic leukemia children in Beijing Boren Hospital. The study will be approved by the institutional review board of Beijing Boren Hospital, and informed consent will be obtained in accordance with the Declaration of Helsinki. All these participants will be matched the diagnostic criteria for (r/r) B-ALL according to the WHO classification and complete morphological evaluation, immunophenotype analysis by flow cytometry (FCM), cytogenetic analysis by routine G-banding karyotype analysis and leukemia fusion gene screening by multiplex nested reverse transcriptase-polymerase chain reaction (PCR). Participants will be eligible if they are heavily treated B-ALL who failed from re-induction chemotherapy after relapse or continued MRD+ for more than three months, and had positive CD19 and CD22 expressions on leukemia blasts by FCM (>95% CD19 and >95% CD22). After CAR T-cell infusion, clinical outcomes including overall survival (OS), disease-free survival (DFS), adverse effects and relapse will be evaluated.

Conditions

Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia, in Relapse; Refractory Acute Lymphoid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

chimeric antigen receptor T cell treatment

Group Type: EXPERIMENTAL

chimeric antigen receptor T cell

Intervention Type: BIOLOGICAL

CAR-T cells were manufactured from peripheral blood mononuclear cells collected by leukapheresis and frozen for multiple uses. Before each CAR T-cell infusion (day 0), patients received lymphodepleting chemotherapy composing of Fludarabine (30 mg/m2/day) and Cyclophosphamide (250 mg/m2/day) on days -5 to -3. No bridging chemotherapy was given between enrollment and infusion. In sequential CAR-T clinical trials, CAR-T cells will be given twice（anti-CD19 CAR-T first, then anti-CD22 CAR-T). All patients underwent bone marrow (BM) biopsy examination and radiology studies on days 30 and every month to determine the response and remission status. Bone biopsy, MRD status by FCM and RT-PCR (if the patient had fusion gene), and EMDs evaluation by CT/MRI/PET-CT were also conducted before CAR-T cell infusion to determine the disease status.

Interventions

chimeric antigen receptor T cell

CAR-T cells were manufactured from peripheral blood mononuclear cells collected by leukapheresis and frozen for multiple uses. Before each CAR T-cell infusion (day 0), patients received lymphodepleting chemotherapy composing of Fludarabine (30 mg/m2/day) and Cyclophosphamide (250 mg/m2/day) on days -5 to -3. No bridging chemotherapy was given between enrollment and infusion. In sequential CAR-T clinical trials, CAR-T cells will be given twice（anti-CD19 CAR-T first, then anti-CD22 CAR-T). All patients underwent bone marrow (BM) biopsy examination and radiology studies on days 30 and every month to determine the response and remission status. Bone biopsy, MRD status by FCM and RT-PCR (if the patient had fusion gene), and EMDs evaluation by CT/MRI/PET-CT were also conducted before CAR-T cell infusion to determine the disease status.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Patients who were diagnosed as primary refractory or relapsed B-ALL. (Criterion-reference: NCCN, 2020.1); All the patients matched the diagnostic criteria of ALL according to the WHO classification, and conducted morphological evaluation, immunophenotype analysis by flow cytometry (FCM), cytogenetic analysis by routine G-banding karyotype analysis, screen of 56 leukemia-related fusion genes by multiplex nested reverse transcriptase polymerase chain reaction (RT-PCR), and quantification of fusion genes by real-time PCR with ABL1 as reference. 339 hematological malignancies-related genes were also screened by Illumina sequencing. Extramedullary diseases (EMDs) were confirmed CD19+ and CD22+ by FCM and evaluated by positron emission tomography/computed tomography (PET/CT), CT, MRI or ultrasonography. The patient relapsed during chemotherapy, failed from re-induction chemotherapy (including first and second generation TKIs) after relapse or had a persistent positive MRD for three months or relapsed after allo-HCT. Patients had positive CD19 and CD22 expression on leukemia blasts by FCM (>95% CD19 and CD22 positive);
• Age from 1 to 18 years old;
• Children candidates can be recruited after the legal guardian or patient advocate has signed the treatment consent form and voluntary consent form.

Exclusion Criteria

• Intracranial hypertension or unconscious;
• Acute heart failure or severe arrhythmia;
• Acute respiratory failure;
• Other types of malignant tumors;
• Diffuse intravascular coagulation;
• Serum creatinine and/or blood urea nitrogen over 1.5 times than normal range;
• Sepsis or other uncontrolled infection;
• Uncontrolled diabetes mellitus;
• Severe psychological disorder;
• Obvious cranial lesions with cranial MRI;
• More than 20 counts/ul leukemic cells in cerebrospinal fluid;
• More than 30% leukemic cells in the blood;
• Stage III WHO/ECOG score;
• Organ recipients;
• Pregnant or breastfeeding;
• Active, uncontrolled infection, including hepatitis B, hepatitis C or human immunodeficiency virus (HIV);

• Minimum Eligible Age: 0 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Boren Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Beijing Boren Hospital

Beijing, Beijing Municipality, China

Countries

China

References

Pan J, Tang K, Luo Y, Seery S, Tan Y, Deng B, Liu F, Xu X, Ling Z, Song W, Xu J, Duan J, Wang Z, Li C, Wang K, Zhang Y, Yu X, Zheng Q, Zhao L, Zhang J, Chang AH, Feng X. Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2023 Nov;24(11):1229-1241. doi: 10.1016/S1470-2045(23)00436-9. Epub 2023 Oct 17.

Reference Type: DERIVED

PMID: 37863088 (View on PubMed)

Other Identifiers

BR-1922-C

Identifier Type: -

Identifier Source: org_study_id