Safety and Efficacy of CD19/CD22 Dual Targeted CAR-T Cell Therapy in R/R B-Cell Acute Lymphoblastic Leukemia

Sponsor

Hebei Senlang Biotechnology Inc., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05225831

Collaborator

Hebei Yanda Ludaopei Hospital (Other)

100

Enrollment

Location

Arm

26.5

Anticipated Duration (Months)

3.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open, single-arm, prospective clinical study to evaluate the safety and efficacy of anti CD19 and CD22 CAR-T cell in the treatment of R/R B-ALL.

Condition or Disease	Intervention/Treatment	Phase
CD19+ and CD 22+ B-ALL	Biological: Autologous CD19/CD22 Chimeric Antigen Receptor T-cells Drug: Cyclophosphamide,Fludarabine	Early Phase 1

Detailed Description

CD19-directed CAR-T cell therapy has shown promising results in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia. CD19 and CD22 are proteins usually expressed on the surface of the B leukemia cells. The dual-CARs enables the T-cells to recognize and kill the tumor cell through recognition of CD19 and CD22.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Safety and Efficacy of CD19/CD22 Dual Targeted CAR-T Cell Therapy in Patients With R/R B-Cell Acute Lymphoblastic Leukemia

Actual Study Start Date :

Aug 15, 2021

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SL19+22 CAR-T Eligible patients will be treated with SL19+22 CAR-T.	Biological: Autologous CD19/CD22 Chimeric Antigen Receptor T-cells A single infusion of CD19 and CD22 CAR-T cells. Other Names: SL19+22 CAR-T Drug: Cyclophosphamide,Fludarabine Given

Arm

Intervention/Treatment

Experimental: SL19+22 CAR-T

Eligible patients will be treated with SL19+22 CAR-T.

Biological: Autologous CD19/CD22 Chimeric Antigen Receptor T-cells

A single infusion of CD19 and CD22 CAR-T cells.

Other Names:

SL19+22 CAR-T

Drug: Cyclophosphamide,Fludarabine

Given

Outcome Measures

Primary Outcome Measures

Safety: Incidence of adverse events [up to 28 days]
To evaluate the possible adverse events that could occurred within the first month post SL19+22 infusion, including symptoms such as cytokine release syndrome and neurotoxicity.
Efficacy: Remission Rate [Up to 3 months]
Remission Rate includes complete remission(CR)、CR with incomplete blood count recovery(CRi)、No remission(NR)

Secondary Outcome Measures

Efficacy:duration of response (DOR) [24 months post CAR-T cells infusion]
Duration of response
Efficacy: progression-free survival (PFS) [24 months post CAR-T cells infusion]
progression-free survival (PFS) time
CAR-T proliferation [3 months post CAR-T cells infusion]
the copy number of CD19 and CD22 CAR- T cells in the genomes of peripheral blood mononuclear cell (PBMC) by quantitative Real-time PCR (qPCR).
Cytokine release [First month post CAR-T cells infusion]
Cytokine( IL-6,IL-10,IFN-γ,TNF-α ) concentration (pg/mL) by flow cytometry

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Sign the informed consent and be willing and able to comply with the visit, treatment regimen, laboratory examination and other requirements of the study as stipulated in the trial flow chart;
A definite diagnosis of B-cell Lymphocyte Leukemia, which meets any of the following criteria: Relapsed : a) relapsed within 12 months after first remission;Refractory: a) no remission after six weeks of induction therapy or no remission after two courses of induction therapy; b) relapsedafter CR for 2 or more times; c) The first relapse after chemotherapy and no remission after at least one salvage treatment; c) relapsed after hematopoietic stem cell transplantation;
ECOG Scores: 0~2
CD19 positive and CD22 positive were detected by immunohistochemistry or flow cytometry;
Estimated survival time>3 months;
Peripheral blood mononuclear immune cells must be collected at least 2 weeks after the last radiotherapy or systemic treatment.
For patients with only extramedullary recurrence of B-ALL, there must be at least one assessable lesion.

Exclusion Criteria:

Serious cardiac insufficiency；
Has a history of severe pulmonary function damaging;
Presence of other malignant tumors.
Presence of active fungal, bacterial, viral, or other infection requiring IV antibiotics for management.
Presence of other severe autoimmune diseases or immunodeficiency disease;
Patients with active hepatitis B or hepatitis C([HBVDNA+]or [HCVRNA+]);
Known positive serology for human immunodeficiency virus (HIV) or syphilis。
Has a history of serious allergies on biological products (including antibiotics);
Female patients who are under pregnancy and/or lactation, or planing on pregnancy for the next 12 months.
Any other situations that the researchers believe will affect the results of the study.