MB-CART19.1 in Relapsed/Refractory Acute Lymphoblastic Leukemia

Официальное название

MB-CART19.1 in Patients With Relapsed/Refractory CD19-positive B Cell Acute Lymphoblastic Leukemia: A Feasibility Study

Обзор

Single-arm, prospective, open-label feasibility study evaluating the technical and operational feasibility of manufacturing autologous CD19-directed CAR-T cells (MB-CART19.1) at the point of care for the treatment of relapsed or refractory B-ALL in pediatric and adult patients.

Вмешательства

• Генная терапия MB-CART19.1
  All participants will undergo leukapheresis for collection of autologous T cells, which will then be manufactured into MB-CART19.1 on-site using CliniMACS Prodigy platform. Successfully manufactured MB-CART19.1 products will be infused back to the patient following a lymphodepleting chemotherapy regimen.

Первичные конечные точки

• Proportion of enrolled patients for whom MB-CART19.1 product is successfully manufactured on-site and meets release criteria. [Срок оценки: From patient enrollment through completion of manufacturing and release testing; estimated 2-4 weeks per patient and up to 12 months for the full cohort.]

Вторичные конечные точки (7)

• Overall response rate (ORR) (CR, CR with incomplete hematologic recovery (CRh)) on day 28. [Срок оценки: Up to approximately 28 days after the last patient infusion.]
• Duration of response time from first documented response to progression or death up to 12 months post-infusion [Срок оценки: Up to 12 months post-infusion]
• Rate of measurable residual disease (MRD) negativity at 1-, 3-, 6- and 12-month intervals [Срок оценки: at 1-, 3-, 6- and 12-month intervals]
• MB-CART19.1 manufacturing turnaround time [Срок оценки: From leukapheresis to product release (estimated 2 weeks per patient).]
• Overall incidence and severity of adverse events [Срок оценки: From infusion through 12 months post-infusion per patient.]
• Overall incidence and severity of MB-CART19.1- specific adverse events (cytokine release syndrome (CRS)) [Срок оценки: From infusion through 12 months post-infusion per patient.]
• Overall incidence and severity MB-CART19.1-specific adverse events (Immune effector cell associated neurotoxicity syndrome (ICANS)) [Срок оценки: From infusion through 12 months post-infusion per patient.]

Критерии участия

Критерии включения

• Age ≥ 1 year as long as if deemed fit by treating investigator
• CD19 expression must be detected (≥20%) on the malignant cells by flow cytometry.
• Patients with relapsed or refractory disease with 0.01% or higher blasts in the bone marrow, or patients with confirmed disease progression as demonstrated by FDG PET-CT or CT/MRI of the affected lymph node or spleen after at least 2 cycles/lines of chemotherapy are eligible for enrollment. For patients with Philadelphia-positive disease, a second-generation or higher TKI must have been utilized in one of the treatment lines.
• Patients who have relapsed post alloSCT at least 100 days post-transplant, with no evidence of active graft vs host disease, and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
• Estimated life expectancy > 12 weeks
• Karnofsky or Lansky (age dependent) performance score ≥ 60
• Patients and/or parents must give their written informed consent/assent.
• CNS and/or testicular involvement are allowed, only if cleared and in the presence of systemic involvement.

Критерии исключения

• Rapidly progressive, uncontrolled disease as assessed by the treating physician and/or principal investigator.
• Persistent extramedullary disease.
• Isolated CNS and/or testicular disease.
• Current autoimmune disease, or history of autoimmune disease with potential CNS involvement
• Active hepatitis B, C or HIV
• Active clinically significant CNS dysfunction (including but not limited to uncontrolled seizure disorders, cerebrovascular ischemia or hemorrhage, dementia, paralysis)
• History of an additional malignancy (≤ 3 years) other than non-melanoma skin cancer or carcinoma in situ.
• Pulmonary function: Patients with pre-existing severe lung disease (FEV1 or FVC < 65%) or an oxygen requirement of >28% O2 FiO2 or active pulmonary infection.
• Cardiac function: Left ventricular ejection fraction <50% by echocardiography
• Renal function: Creatinine clearance <50 mL/min/1.73 m2
• Liver function: patients with serum bilirubin ≥3 times upper limit of or AST or ALT > 5 times upper limit of normal, unless due to leukemic liver infiltration as determined by the investigators.
• Pregnant or breast-feeding females
• Medications: systemic chemotherapies, corticosteroids with the exception of physiologic replacement dosing (<0.5 mg/kg/day of methylprednicone), tyrosine kinase inhibitors (TKI) within 7 days prior to leukapheresis, Fludarabine/clofarabine or immunosuppressive drugs and antibodies (e.g. rituximab, blinatumomab) or investigational drugs or donor lymphocyte

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

Иордания · 1 центр

• King Hussein Cancer Center — Amman

Идентификаторы

NCT: NCT07371403 · 25KHCC164

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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