CD19 Negative B-cell Malignancies Clinical Trial
Official title:
4SCAR-T Therapy After Anti-CD19 Immunotherapy Targeting B Cell Acute Lymphoblastic Leukemia
This study will evaluate safety and efficacy of a combination of 4th generation chimeric antigen receptor gene-modified T cells (4SCAR-T) targeting CD19-negative B-ALL that express alternative surface antigens such as CD22, CD10, CD20, CD38, and CD123, as many patients relapse after anti-CD19 immunotherapy. Clinical response and optiminzation of a standardized lentiviral vector and cell production protocol will be investigated. This is a phase I/II trial enrolling patients from multiple clinical centers.
Anti-CD19 immunotherapy based on antibody conjugated drugs or CD19-CAR-T cells has
demonstrated unprecedented positive response in relapsing/refractory B-cell acute
lymphoblastic leukemia (r/r B-ALL). However, many patients still relapse and up to 30-50% of
those relapses are characterized by the loss of CD19 surface antigen. Patients with
CD19-negative relapse usually have a poor prognosis. The mechanisms underlying CD19-negative
relapses are not fully understood and it is important to develop solutions to supplement
post-CD19 immunotherapies.
Potential markers for recurrent leukemic blasts in an emerging CD19-negative blast population
include many known B-cell lineage antigens. To prevent further target escape and improve the
therapeutic effects, the 4th generation CAR gene-modified T cells targeting CD22, CD10, CD20,
CD38, or CD123 have been considered in post anti-CD19 treatment. This study aims to evaluate
safety and efficacy of administrating one or multiple non-CD19 targeting CAR-T cells to
patients with CD19-escaped B cell malignancies.
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