This is a Phase I/II Interventional, Open-label Treatment Study Designed to Evaluate the Safety and Efficacy of Anti CD 19/22 CAR- T Cells Immunotherapy for Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia/Lymphoma.

Официальное название

Phase I/II Open-label Study Evaluating The Safety And Efficacy of Anti CD19/22 CAR-T Cells Therapy Adults With R/ R Leukemia/ Lymphoma

Обзор

The purpose of this study is to estimate the safety and the efficacy of anti-CD19/22 CAR- T cells immunotherapy for adults with relapsed or refractory acute lymphoblastic leukemia/lymphoma.

Подробное описание

Locally manufactured second generation autologous CD19/22 CAR-T cells are used for immunotherapy. Protocol treatment includes leukapheresis in order to harvest T cells, lymphodepleting conditioning (fludarabine + cyclophosphamide) followed by one dual targeting CAR-T cells infusion.

The Main research objectives of the Phase I:

To preliminarily explore the safety (incidence of CRS, ICANS, HLH, infections, late ICAHT, and cytopenias) and tolerability.

The Secondary research objectives of the Phase I:

To explore the pharmacokinetics of CAR-T cells.

The Main research objectives of the Phase II:

Overall response rate, including complete response (CR) and partial response (PR) rates.

The Secondary research objectives of the Phase II:

Duration of response (DOR). Progression-free survival rates. Overall survival rates.

Вмешательства

• Биопрепарат CD19/22 CAR-T cells
  Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with doses from 50 x 10⁶ to 150 x 10⁶ CD19/CD22 CAR-T cells

Первичные конечные точки

• Phase I. Safety [Срок оценки: 1 month post CAR-T cells infusion]
• Phase II. Overall response rate [Срок оценки: 3 months post CAR-T cells infusion]

Вторичные конечные точки (4)

• Phase I. CAR-T proliferation [Срок оценки: 3 months post CAR-T cells infusion]
• Phase II. Efficacy: Overall survival rates [Срок оценки: 12 months post CAR-T cells infusion]
• Phase II. Progression-free survival rates [Срок оценки: 12 months post CAR-T cells infusion]
• Phase II. Duration of response [Срок оценки: 12 months post CAR-T cells infusion]

Критерии участия

Критерии включения

• Male or female, aged ≥18 years.
• Willing and able to give written, informed consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.
• Relapsed or refractory lymphoblastic leukemia/lymphoma.

\- Chemotherapy-refractory disease after ≥1 lines of therapy

\- Relapse after chemotherapy or after ASCT/Allo-HSCT.

• Adequate organ system function including - Creatinine clearance ≥40 cc/min.

\- Serum alanine aminotransferase / aspartate aminotransferase ≤2.5 x upper limit of normal (ULN).

\- Total bilirubin ≤1.5 x ULN, except in subjects with Gilbert's syndrome.

\- Left ventricular ejection fraction (LVEF) ≥50% (by echocardiogram \[ECHO\] or

\- Baseline oxygen saturation >92% on room air and ≤Grade 1 dyspnoea.

• Have no active GVHD (Grade 2-4)
• Adequate bone marrow (BM) function - Absolute neutrophil count ≥1.0 × 10\^9/L.

• Absolute lymphocyte count ≥0.3 × 10\^9/L (at enrolment and prior to leukapheresis).
• Haemoglobin ≥80 g/L.
• Platelets ≥75 × 10\^9/L

7\. The expression of CD19 and/or CD22 on the tumor cells are reported as positive by either immunohistochemistry or flow cytometry

Критерии исключения

• Females who are pregnant or lactating.
• History or presence of clinically relevant CNS pathology such as epilepsy, paresis, aphasia, stroke within prior 3 months, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis.
• Patients with active CNS involvement by malignancy. Patients with history of central nervous system (CNS) involvement with malignancy may be eligible if CNS disease has been effectively treated and provided treatment was at least 4 weeks prior to enrolment (at least 8 weeks prior to CAR-T infusion).
• Clinically significant, uncontrolled heart disease or a recent (within 12 months) cardiac event.
• Active bacterial, viral or fungal infection requiring systemic treatment. Active or latent hepatitis B infection or hepatitis C infection. Testing positive for human immunodeficiency virus, human T cell lymphotropic virus (HTLV1 and 2) or syphilis.
• History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 24 months.

6\. Evidence of active pneumonitis on chest computed tomography (CT) scan at screening or history of drug-induced pneumonitis, idiopathic pulmonary fibrosis, organising pneumonia, or idiopathic pneumonitis.

7\. History of other malignant neoplasms unless disease free for at least 24 months (carcinoma in situ, non-melanoma skin cancer, breast or prostate cancer on hormonal therapy allowed).

8\. The following medications are excluded:

• Steroids: Therapeutic doses of corticosteroids within 7 days of leukapheresis or 72 hours prior to CAR-T administration. However, physiological replacement, topical, and inhaled steroids are permitted.
• Immunosuppression: Immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis or CAR-T cells infusion.
• Cytotoxic chemotherapies within 1 week of CAR-T cellsinfusion and 1 week prior to leukapheresis.
• Antibody therapy use including anti-CD20/19/22 therapy within 2 weeks prior to CAR-T cells infusion.
• Granulocyte-colony stimulating factor less than 14 days prior to leukapheresis.
• Live vaccine ≤4 weeks prior to enrolment.
• Prophylactic intrathecal therapy: Methotrexate within 4 weeks and other intrathecal chemotherapy (e.g. Ara-C) within 2 weeks prior to starting pre-conditioning chemotherapy.

Prior limited radiation therapy within 2 weeks of CAR-T cells infusion. 9. Known allergy to albumin, dimethyl sulphoxide (DMSO), cyclophosphamide or fludarabine or tocilizumab.

10\. Any other condition that in the Investigator's opinion would make the patient unsuitable for the clinical trial.

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

Беларусь · 1 центр

• State Institution Minsk Scientific and Practical Center for Surgery, Transplantology, and — Minsk

Идентификаторы

NCT: NCT07162571 · 23.25

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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