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Phase II Study of Anti-CD19 CAR-T Cells Treating Leukemia Children

Primary Purpose

Acute Lymphoblastic Leukemia, Pediatric, Acute Lymphoblastic Leukemia, in Relapse, Refractory Acute Lymphoblastic Leukemia

Status

Recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Murine autologous anti-CD19 chimeric antigen receptor T cells

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia, Pediatric

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. 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. Extramedullary diseases (EMDs) were confirmed CD19+ by FCM and evaluated by positron emission tomography/computed tomography (PET/CT), CT, MRI or ultrasonography. The patient relapsed during chemotherapy or failed from re-induction chemotherapy (including first and second-generation TKIs) after relapse or had a persistent positive minimal residual disease (MRD) for three months. Patients had positive CD19 expression on leukemia blasts by FCM (>95% CD19 positive);
Age from 0 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 HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Autologous Murine Anti-CD19 CAR-T treatment

Arm Description

Outcomes

Primary Outcome Measures

CR rate

The complete remission(CR) rate to the CAR-T treatment

Secondary Outcome Measures

Full Information

NCT ID

NCT04325841

First Posted

March 26, 2020

Last Updated

August 12, 2022

Sponsor

Beijing Boren Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04325841

Brief Title

Phase II Study of Anti-CD19 CAR-T Cells Treating Leukemia Children

Official Title

Phase II Study of Autologous Murine Anti-CD19 Chimeric Antigen Receptor T Cells Treating Refractory or Relapsed B Acute Lymphoblastic Leukemia Children

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

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

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The investigators will conduct a phase II clinical trial of autologous murine anti-CD19 chimeric antigen receptor T cells treating refractory or relapsed B 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 expression on leukemia blasts by FCM (>95% CD19). 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, Pediatric, Acute Lymphoblastic Leukemia, in Relapse, Refractory Acute Lymphoblastic 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

Autologous Murine Anti-CD19 CAR-T treatment

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

Murine autologous anti-CD19 chimeric antigen receptor T cells

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 CD19 T cell clinical trials, CAR-T cells was given once. 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

CR rate

Description

The complete remission(CR) rate to the CAR-T treatment

Time Frame

1 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

0 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients who were diagnosed as primary refractory or relapsed B-ALL. 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. Extramedullary diseases (EMDs) were confirmed CD19+ by FCM and evaluated by positron emission tomography/computed tomography (PET/CT), CT, MRI or ultrasonography. The patient relapsed during chemotherapy or failed from re-induction chemotherapy (including first and second-generation TKIs) after relapse or had a persistent positive minimal residual disease (MRD) for three months. Patients had positive CD19 expression on leukemia blasts by FCM (>95% CD19 positive); Age from 0 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);

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jing Pan, Master

Phone

+8618911067969

panj@borenhospital.com

Facility Information:

Facility Name

Beijing Boren Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Jing Pan, Master

Phone

+8618911067969

panj@borenhospital.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Phase II Study of Anti-CD19 CAR-T Cells Treating Leukemia Children

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