Allo HSCT for High Risk Hemoglobinopathies

Официальное название

Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathies and Other Red Cell Transfusion Dependent Disorders

Обзор

A single center, open label, interventional, phase II trial for donor transplant for high risk hemoglobinopathies and other red cell transfusion dependent disorders utilizing allogeneic hematopoietic stem cell transplantation (HSCT) regimens.

Вмешательства

• Препарат Alemtuzumab
  Alemtuzumab (Campath) will be administered IV over 2 hours on day -8 to day -4.
• Лучевая терапия Total Body Irradiation
  400 cGy in 2 split fractions will be administered per Department of RadiationOncology SOPs.
• Биопрепарат Cell Infusion
  On day 0 the cells will be infused per cell source specific institutional guidelines
• Препарат Thymoglobulin
  ATG will be administered IV every 24 hours beginning on day -8 for all patients. Dosing will be model-based using Bayesian methodology13,14,15. Total doses and total number of doses (1-4 doses) will be determined based on absolute lymphocyte count and weight.
• Препарат Fludarabine
  Fludarabine will be administered IV over 1 hour every 24 hours on day -5 to day - 2. The daily dose of fludarabine will be determined by model-based dosing utilizing Bayesian methodology with a cumulative area under the curve (cAUC) of 20 mg\*hr/L (range 18-22 mg\*hr/L).
• Препарат Busulfan
  Busulfan dosing and administration and therapeutic drug monitoring (TDM) per institutional guidelines. Initial busulfan dosing will be determined by model-based dosing utilizing Bayesian methods with a cumulative area under the curve (cAUC) of 75 mg\*hr/L.
• Препарат Cyclophosphamide
  Cyclophosphamide will be administered at a dose of 14.5 mg/kg over 2 hours IV daily on days -6 and -5. Cyclophosphamide dosing is calculated based on actual body weight (ABW). For Arm D - Cyclophosphamide 50 mg/kg IV will be administered over 2 hours on days +3 and +4. Cyclophosphamide dosing for post-transplant is calculated based on ideal body weight (IBW) unless patient weighs less than IBW, in which case actual body weight (ABW) will be used.
• Препарат Sirolimus
  Patients on Arm A and Arm D will receive sirolimus; beginning on day -3 and continuing until day +180 for patients on Arm A or beginning on day +5 and continuing until 1 year post transplant for patients on Arm D.
• Препарат Tacrolimus
  Patients on Arm B and Arm C will receive tacrolimus, beginning on day -3 and continuing until day +180. Tacrolimus dosing and monitoring will be per institutional guidelines.
• Препарат Mycophenolate Mofetil
  MMF will begin on day -3 (Arm A, B \& C) or day +5 (Arm D). Patients treated on adult service will receive 15 mg/kg (max 1500 mg/dose) given every 12 hours, rounded to nearest 250 mg. Patients on pediatric service will receive 15 mg/kg (max 1000 mg/dose) given every 8 hours. MMF dosing will be monitored and altered as clinically appropriate based on institutional guidelines. MMF will be stopped at day +30 (Arms A, B \& C) or day +35 (Arm D) or 7 days after engraftment, whichever day is later, if

Первичные конечные точки

• Incidence of Graft versus Host Disease (GvHD) [Срок оценки: 1 year]

Вторичные конечные точки (4)

• Overall Survival [Срок оценки: 1 and 2 years]
• Grade 3-4 Acute GvHD [Срок оценки: 2 years]
• Chronic Graft versus Host Disease (GvHD) Free [Срок оценки: 2 years]
• Failure Free Survival [Срок оценки: 2 years]

Критерии участия

Критерии включения

• Sickle Cell Disease (SCD)
• SCD Patients with a fully matched sibling donor (MSD) irrespective of the frequency or severity of symptoms MSD transplant can be considered. Parents/patient must be counseled as to the risks and benefits and provide their voluntary informed consent
• Transfusion Dependent Alpha- or Beta- Thalassemia
• Diamond Blackfan Anemia
• Other Non-Malignant Hematologic Disorders
• Karnofsky ≥ 60%, Lansky play score ≥ 60. Patients with lower performance score can be considered based on study team's evaluation.
• Sexually active persons of childbearing potential or persons with partners of childbearing potential must agree to use a highly effective form of contraception during study treatment and for at least 4 months after the transplant.

Критерии исключения

• Pregnant, breastfeeding or intending to become pregnant during the study. Persons of childbearing potential must have a negative pregnancy test (serum or urine) within 30 days of the start of treatment
• HIV infection with a detectable viral load. All HIV+ patients must be evaluated by infectious disease (ID) and an HIV management plan established prior to transplantation.
• Active, uncontrolled infection - infection that is stable or improving after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections) will be permitted
• Known allergy to any of the study components
• Psychiatric illness/social situations that, in the judgement of the enrolling Investigator, would limit compliance with study requirements
• Other illness or a medical issue that, in the judgement of the enrolling Investigator, would exclude the patient from participating in this study

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 1 центр

• Masonic Cancer Center — Minneapolis

Идентификаторы

NCT: NCT06872333 · 2024LS140

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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