Study of Sequential CAR-T Cell Treating Leukemia Children

Phase II Study of Sequential Chimeric Antigen Receptor T Cell Targeting at Different B-cell Antigens Treating Refractory or Relapsed B-cell Acute Lymphoblastic Leukemia Children

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Lymphoblastic Leukemia; Acute Lymphoblastic Leukemia, in Relapse; Refractory Acute Lymphoid Leukemia
• Intervention / Treatment: Biological: chimeric antigen receptor T cell

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jing Pan, Master; Phone Number: +8618911067969; Email: panj@borenhospital.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Beijing Boren Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: chimeric antigen receptor T cell treatment

Biological: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	according to NCCN, Complete response (CR), CR with incomplete blood count recovery(CRi) .	during three months (±1 week) post CD19 CAR T-cell infusion

Collaborators and Investigators

• Sponsor: Beijing Boren Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: April 8, 2020
• First Submitted That Met QC Criteria: April 8, 2020
• First Posted (Actual): April 9, 2020

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

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; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
• Other Study ID Numbers: BR-1922-C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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