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Study of Sequential CAR-T Cell Treating Leukemia Children

Primary Purpose

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

Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
chimeric antigen receptor T cell
Sponsored by
Beijing Boren Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

0 Years - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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);

Sites / Locations

  • Beijing Boren Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

chimeric antigen receptor T cell treatment

Arm Description

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
according to NCCN, Complete response (CR), CR with incomplete blood count recovery(CRi) .

Secondary Outcome Measures

Full Information

First Posted
April 8, 2020
Last Updated
August 1, 2023
Sponsor
Beijing Boren Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04340154
Brief Title
Study of Sequential CAR-T Cell Treating Leukemia Children
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
May 1, 2020 (Actual)
Primary Completion Date
May 1, 2024 (Anticipated)
Study Completion Date
November 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing Boren Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia, in Relapse, Refractory Acute Lymphoid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
chimeric antigen receptor T cell treatment
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
chimeric antigen receptor T cell
Intervention Description
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.
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
according to NCCN, Complete response (CR), CR with incomplete blood count recovery(CRi) .
Time Frame
during three months (±1 week) post CD19 CAR T-cell infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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);
Facility Information:
Facility Name
Beijing Boren Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100000
Country
China

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of Sequential CAR-T Cell Treating Leukemia Children

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