A Study of CTA101 UCAR-T Cell Injection in Patients With Relapsed or Refractory CD19+ B-line Hematological Malignancy

Обзор

A study of CTA101 UCAR-T cell injection in patients with relapsed or refractory CD19+ B-line hematological malignancy

Подробное описание

This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory CD19+ B-line hematological malignancy: B-ALL and B-NHL. the selection of dose levels and the number of subjects are based on clinical tiral of similar foreign products. 2 groups of patients will be enrolled, 36 in each group. Primary objective is to explore the safety, main consideration is dose-related safety.

Вмешательства

• Препарат CTA101
  CTA101 UCAR-T cell injection by intravenous infusion

Первичные конечные точки

• Dose-limiting toxicity (DLT) [Срок оценки: Baseline up to 28 days after CTA101 infusion]
• Incidence of treatment-emergent adverse events (TEAEs) [Срок оценки: Up to 2 years after CTA101 infusion]

Вторичные конечные точки (6)

• B-cell acute lymphocytic leukemia (B-ALL), MRD negative overall response rate (MRD- ORR) [Срок оценки: 3 months]
• B-ALL, Event-free survival (EFS) [Срок оценки: Month 6, 12, 18 and 24]
• B-ALL, Overall response rate (ORR) [Срок оценки: Month 6, 12, 18 and 24]
• B-ALL, Overall survival (OS) [Срок оценки: Month 6, 12, 18 and 24]
• B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR) [Срок оценки: weeks 4, 12, months 6, 12, 18 and 24]
• B-NHL,disease control rate (DCR) [Срок оценки: weeks 12, months 6, 12, 18 and 24]

Критерии участия

Критерии включения

Inclusion criteria applicable to ALL only:

• Male or female aged ≥ 3 and <70 years old;
• Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);
• Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):

• CR not achieved after standardized chemotherapy;
• CR achieved following the first induction, but CR duration is ≤ 12 months;
• Ineffective after first or multiple remedial treatments;
• 2 or more recurrences;
• The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is >5% (morphology) and/or >1% (Flow cytometry);
• Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;

Inclusion criteria applicable to NHL only:

• Male or female aged ≥ 18 and <70 years old;
• Histologically confirmed diagnosis per WHO Classification Criteria for Lymphocytic Tumors 2016, including DLBCL(NOS), follicular lymphoma, Chronic lymphoblastic leukemia/small lymphoblastic lymphoma transforms DLBCL, PMBCL and high grade B cell lymphoma;
• Relapsed or refractory DLBCL (meeting one of the following conditions):

• No remission or recurrence after receiving second-line or above second-line chemotherapy;
• Primary drug resistance;
• Recurrence after autologous hematopoietic stem cell transplantation
• According to Lugano 2014, there should be at least one evaluable tumor lesion.

Applicable standards for ALL and NHL:

• HLA antibody(-) or HLA antibody(+) and HLA donor specific antibody(DSA)(-);
• total bilirubin ≤ 51umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8umol/L;
• Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
• No active infection in the lungs, blood oxygen saturation by sucking air is ≥ 92%;
• Estimated survival time ≥ 3 months;
• ECOG performance status 0 to 2;
• Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Критерии исключения

• patients with extramedullary lesions, except those with CNSL (CNS-1) under effective control (for ALL patients only);
• Confirmed diagnosis of lymphoblastic crisis of chronic myeloid leukemia, Burkitt's leukemia/lymphoma per WHO Classification Criteria (for ALL patients only);
• Patients with hereditary syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome (for ALL patients only);
• patients with intracranial extralateral lesions (cerebrospinal fluid tumor cells and/or intracranial lymphoma invasion shown by MRI) (for NHL patients only) ;
• extensive involvement of gastrointestinal lymphoma (for NHL patients only);
• radiotherapy, chemotherapy and monoclonal antibody within 1 week before screening;
• Have a history of allergy to any of the components in the cell products;
• Prior treatment with any CAR T cell product or other genetically-modified T cell therapies;
• According to the New York heart association (NYHA) cardiac function classification criteria, Subjects with grade III or IV cardiac insufficiency;
• Myocardial infarction, cardioangioplasty or stenting, unstable angina pectoris, or other severe cardiac diseases within 12 months of enrollment;
• Severe primary or secondary hypertension of grade 3 or above (WHO Hypertension Guidelines, 1999);
• Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
• History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
• Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis).
• Indwelling catheters in vivo (e.g. percutaneous nephrostomy, Foley catheter, bile duct catheter, or pleural/peritoneal/pericardial catheter). Ommaya storage, dedicated central venous access catheters such as Port-a-Cath or Hickman catheters are allowed;
• History of other primary cancer, except for the following conditions:

• Cured non-melanoma after resection, such as basal cell carcinoma of the skin;
• Cervical cancer in situ, localized prostate cancer, ductal cancer in situ with disease-free survival ≥ 2 years after adequate treatment;
• Patients with autoimmune diseases requiring treatment, patients with immunodeficiency or requiring immunosuppressive therapy;
• Patients with graft-versus-host disease (GVHD);
• Prior immunizations with live vaccine 4 weeks prior to screening;
• History of alcoholism, drug abuse or mental illness;
• If HBsAg positive at screening, HBV DNA copy number detected by PCR in patients with active hepatitis B > 1000 (if HBV DNA copy number≤1000, routine antiviral therapy is required after enrollment), as well as CMV, hepatitis C, syphilis infection;
• Concurrent therapy with systemic steroids within 1 week prior to screening, except for the patients recently or currently receiving inhaled steroids;
• Patients who have participated in any other clinical studies within 2 weeks prior to screening;
• pregnant and breast-feeding women and the subjects who are fertile and unable to take effective contraceptive measures (regardless of the gender);
• Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

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

• The First Hospital of Zhejiang Medical Colleage Zhejiang University — Ханчжоу

Идентификаторы

NCT: NCT04227015 · BHCT-CTA101-08

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗