4SCAR-T Therapy Post CD19-targeted Immunotherapy

Официальное название

4SCAR-T Therapy After Anti-CD19 Immunotherapy Targeting B Cell Acute Lymphoblastic Leukemia

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат Infusion of 4SCAR-T specific to CD22/CD123/CD38/ CD10/CD20
  Patients who have relapsed after anti-CD19 immunotherapy or have CD19 negative B cell malignancies

Первичные конечные точки

• Safety of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells [Срок оценки: 24 weeks]

Вторичные конечные точки (1)

• Anti-tumor activity of fourth generation anti-CD22/CD123/CD38/CD10/CD20 CAR-T cells [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Age older than 6 months.
• B cell malignancies relapsed after anti-CD19 immunotherapy.
• Malignant B cells expressing one or more of the following surface molecules: CD22/CD123/CD38/CD10/CD20.
• The KPS score over 80 points, and survival time is more than 1 month.
• Greater than Hgb 80 g/L.
• No contraindications to blood cell collection.

Критерии исключения

• Complications with other active diseases, and difficult to assess patient response.
• Bacterial, fungal, or viral infection unable to control.
• Living with HIV.
• Active HBV and HCV infection.
• Pregnant and nursing mothers.
• Under systemic steroid use within a week of the treatment.
• Judged difficult to cooporate for continued evaluation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shenzhen Geno-Immune Medical Institute — Шэньчжэнь

Идентификаторы

NCT: NCT04430530 · GIMI-IRB-20008

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗