Intensity Modulated Total Marrow Irradiation in Fully Human Leukocyte Antigen (HLA)-Matched and Partially-HLA Mismatched Allogeneic Transplantation Patients With High-Risk Acute Myeloid Leukemia (AML), Chronic Myeloid Leukemia (CML), and Myelodysplastic Syndrome (MDS)

Официальное название

A Phase II Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) in Addition to Myeloablative Fludarabine/Busulfan and Post-Transplant Cyclophosphamide (PTCY) for Fully Human Leukocyte Antigen (HLA)-Matched and Partially-HLA Mismatched Allogeneic Transplantation Patients With High-Risk AML, CML, and MDS

Обзор

The study is a Phase II clinical trial. Patients will receive intensity-modulated total marrow irradiation (TMI) at a dose of 9 Gray (Gy) with standard myeloablative fludarabine intravenous (IV) and targeted busulfan (FluBu4) conditioning prior to allogeneic hematopoietic stem cell transplant (HSCT). Graft-versus-host disease (GVHD) prophylaxis will include Cyclophosphamide on Day +3 and +4, tacrolimus, and mycophenolate mofetil.

Подробное описание

Patients will receive the following conditioning regimen: fludarabine 40 mg/m2 IV piggyback daily, from day -5 (5 days before stem cell infusion) through Day -2, IV busulfan targeting a 4800 μM/min/ day, from day -5 through day -2. In addition to the above chemotherapy, all patients will receive TMI at a dose of 3Gy on days -3, -2, and -1. On day 0, the stem cell product will be infused according to BMT (Bone Marrow Transplant) unit policy. Graft versus host disease (GVHD) prophylaxis will consist of the administration of Cyclophosphamide 50 mg/Kg on days 3 and 4 and mycophenolate mofetil combined with tacrolimus. Post-transplant evaluation will be done per standard care with study data collected at days 30, 60, 90, 180, 365, and 2 years.

Вмешательства

• Лучевая терапия Intensity modulated total marrow irradiation
  See "Treatment Regimen"
• Препарат Cyclophosphamide (CTX)
  This study will determine the safety of the combination of Total Marrow Irradiation (TMI) and Post-Transplant Cyclophosphamide using a myeloablative fludarabine and iv targeted busulfan (Flu/Bu4) conditioning regimen.
• Препарат Fludarabine (Fludara)
  chemotherapy conditioning
• Препарат Busulfan (conditioning for ALLO Transplant)
  chemotherapy conditioning

Первичные конечные точки

• GVHD-Free Relapse-Free Survival after Stem Cell Transplant [Срок оценки: 1 Year Post-Stem Cell Transplant]

Вторичные конечные точки (12)

• Overall Survival [Срок оценки: 2 Years Post-Stem Cell Transplant]
• Time To Engraftment [Срок оценки: 30 Days Post-Stem Cell Transplant]
• Adverse Events [Срок оценки: 30 Days Post-Stem Cell Transplant]
• Adverse Events [Срок оценки: 60 Days Post-Stem Cell Transplant]
• Adverse Events [Срок оценки: 90 Days Post-Stem Cell Transplant]
• Adverse Events [Срок оценки: 180 Days Post-Stem Cell Transplant]
• Adverse Events [Срок оценки: 1 Year Post-Stem Cell Transplant]
• Incidence of Acute Graft Versus Host Disease [Срок оценки: 30 Days Post-Stem Cell Transplant]
• Incidence of Acute Graft Versus Host Disease [Срок оценки: 60 Days Post-Stem Cell Transplant]
• Incidence of Acute Graft Versus Host Disease [Срок оценки: 90 Days Post-Stem Cell Transplant]
• Incidence of Acute Graft Versus Host Disease [Срок оценки: 180 Days Post-Stem Cell Transplant]
• Incidence of Acute Graft Versus Host Disease [Срок оценки: 1 Year Post-Stem Cell Transplant]

Критерии участия

Критерии включения

• 1\. Age 18-65 years.
• 2\. Patients with CML, AML, or MDS who meet one of the following criteria: 2a. Relapsed or refractory AML (including AML in CR2) 2b. Poor-risk AML in first remission, with remission defined as <5% bone marrow blasts morphologically:
• AML arising from MDS, a myeloproliferative disorder, or secondary AML
• Poor risk molecular features according to Leukemia Net including ASXL1, BCOR, EZH2, RUNX1, SF3B1, SRSF2, STAG2, U2AF1, and/or ZRSR2
• Poor-risk cytogenetics: Monosomal karyotype, complex karyotype (> 3 abnormalities), inv (3), t(3;3), t(6;9), MLL rearrangement with the exception of t(9;11), or abnormalities of chromosome 5 or 7. 2c. Primary refractory disease 2d. MDS with at least one of the following poor-risk features:
• Poor-risk cytogenetics including 3q abnormalities, 7/7q minus or complex cytogenetics (>3 abnormalities).
• Current or previous INT-2 or high IPSS score.
• Treatment-related MDS.
• MDS diagnosed before the age of 21 years.
• Progression on or lack of response to standard DNA-methyltransferase inhibitor therapy.
• Life-threatening cytopenias, including those requiring regular PRBC or platelet transfusions. 2e. CML with a history of accelerated or blast phase.

Критерии исключения

• 1\. Presence of significant co-morbidity as shown by:
• 1a. Left ventricular ejection fraction < 50%
• 2b. Creatinine clearance <30ml/min.
• 3c. Bilirubin > 2.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST > 5 x ULN.
• 4d. FEV1 and FVC < 50% of predicted or DLCO <50% of predicted once corrected for anemia.
• 5e. Karnofsky score <70
• 6f. Active viral hepatitis or HIV infection.
• 7g. Cirrhosis.
• 2\. Pregnancy or breast feeding
• 3\. Patients unable to sign informed consent.
• 4\. Patients previously received radiation to >20% of bone marrow-containing areas.

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

США · 1 центр

• University of Illinois Cancer Center — Chicago

Идентификаторы

NCT: NCT06802315 · 2024-0865

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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