A Study of Fludarabine Dosing in Children and Young Adults With B-cell Acute Lymphoblastic Leukemia

Официальное название

Improving EveNt Free Survival by Optimizing FLUdarabine Exposure During LymphodepletioN for CAR T CEll Therapy: a Randomized, Multi-center Study of Children and Young Adults With B-cell Acute Lymphoblastic Leukemia (INFLUENCE)

Обзор

The researchers are doing this study to find out whether PK-targeted fludarabine is an effective Lymphodepletion (LD) chemotherapy approach for people with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) who will receive tisagenlecleucel CAR T-cell therapy. The researchers will compare PK-targeted fludarabine dosing with standard fludarabine dosing to see which treatment approach is more effective. The researchers will also look at whether PK-targeted fludarabine dosing is feasible (practical), the side effects of the study treatment, and how the study treatment affects people's quality of life. The researchers will measure quality of life by having participants complete questionnaires.

Вмешательства

• Препарат Fludarabine
  Fludarabine 30 mg/m2/dose x 4 doses on days -6 to -3 (or -7 to -4)
• Препарат Cyclophosphamide
  All patients will receive Cyclophosphamide 500 mg/m2 IV on days -6 and -5 (or -7 and -6).
• Препарат Fludarabine
  Targeted fludarabine LD: Fludarabine 40 mg/m2/dose x 2 doses on days -6 and -5 (or -7 and -6), with doses on days -4 and -3 (or -5 and -4, if starting lymphodepletion on day -7) adjusted based on PK analysis to target a cumulative area under the curve (AUC) of 18 mg\*h/L (range 17.5-18.5mg\*h/L)
• Биопрепарат CAR-T
  will be infused based on institutional guidelines.

Первичные конечные точки

• compare the event free survival (EFS ) [Срок оценки: 28 days]

Вторичные конечные точки (1)

• survival [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Patients with B-ALL and eligible to receive commercial tisagenlecleucel.
• Patient's weight > 9 kg at time of lymphodepleting chemotherapy
• Adequate organ function at time of LD is required and is defined:

• Hepatic: Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia
• Hepatic: AST and ALT < 5x the upper limit of normal for age, unless thought to be leukemic disease-related
• Renal: Calculated glomerular filtration rate (GFR) ≥ 70 ml/min/1.73m\^2. (based on Schwartz formula GFR (mL/min/1.73 m²) = (36.2 × Height in cm) / Creatinine in mg/dL
• Cardiac: LVEF ≥ 50% by multi-gated acquisition scan (MUGA), resting echocardiogram, or cardiac magnetic resonance imaging (MRI) within 6 weeks of screening
• Pulmonary: Oxygen saturation as recorded by pulse oximetry of ≥ 90% on room air
• Adequate performance status:

• Age ≥ 16 years: ECOG ≤ 1 or Karnofsky > 60% at treatment
• Age < 16 years: Lansky ≥ 60% at treatment
• Willing to participate as research subject and provide written informed consent from parents/legal representative, patient, and age-appropriate assent as appropriate before any study specific screening procedures are conducted, according to local, regional or national law and legislation.

Критерии исключения

• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to the study drugs, or drugs chemically related to study treatment or excipients that contraindicate their participation, including fludarabine, cyclophosphamide and tisagenlecleucel.
• Patients with tisagenlecleucel that is deemed out of specification (OOS) will be excluded from this protocol
• Clinically significant active and uncontrolled infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA etc.)
• Patient/parent/guardian unable to give informed consent or unable to comply with the treatment protocol.
• Pregnant or lactating women

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 5 центров

• Memorial Sloan Kettering Cancer Center — New York
• Cincinnati Children's Hospital Medical Center (Data Collection Only) — Cincinnati
• Children's Hospital of Philadelphia (Data Collection Only) — Philadelphia
• Baylor College Medical Center (Data Collection Only) — Houston
• Texas Children's Hospital (Data Collection) — Houston

Идентификаторы

NCT: NCT07223021 · 25-072

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗