A Randomized Phase II Study of Treosulfan, Fludarabine and Low-Dose TBI as Conditioning for Allogeneic Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)

Fred Hutchinson Cancer Center1 个研究点分布在 1 个国家目标入组 102 人开始时间: 2013年11月最近更新: 2021年6月3日

适应症

干预措施

试验速览

阶段: 2 期
发起方: Fred Hutchinson Cancer Center
入组人数: 102
试验地点: 1
主要终点: Number of Participants That Did Not Progress Within 6 Months

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This randomized phase II trial studies how well treosulfan and fludarabine phosphate, with or without total body irradiation before donor stem cell transplant works in treating patients with myelodysplastic syndrome or acute myeloid leukemia. Giving chemotherapy, such as treosulfan and fludarabine phosphate, and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus before and mycophenolate mofetil after the transplant may stop this from happening.

详细描述

PRIMARY OBJECTIVES:

I. To determine the better of two treosulfan-based conditioning regimens in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), by comparing 6-month progression-free survival.

SECONDARY OBJECTIVES:

I. Determine the effects of two conditioning regimens on changes in gene expression profiles, and evaluate the association of gene expression profiles and disease relapse.

II. Determine the incidence of progression-free survival at 1 year and 2 years after hematopoietic cell transplantation (HCT).

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: — 至 70 Years（Child, Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•MDS, myelodysplastic syndrome/myeloproliferative neoplasia overlap disorders (including chronic myelomonocytic leukemia [CMML], and MDS/myeloproliferative neoplasm [MPN] unclassifiable syndromes)
•AML, other than acute promyelocytic leukemia (APL), in first or second remission or with minimal residual disease
•With Karnofsky index or Lansky Play-Performance scale > 70% on pre-transplant evaluation
•Able to give informed consent (if > 18 years), or with a legal guardian capable of giving informed consent (if < 18 years)
•Patients with previous autologous or allogeneic HCT are allowed to enroll
•DONOR: Human leukocyte antigen (HLA)-identical related donors or
•DONOR: Unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 as defined by high resolution deoxyribonucleic acid (DNA) typing; mismatch for one HLA allele is allowed
•DONOR: Donors able to undergo peripheral blood stem cell collection or bone marrow harvest
•DONOR: Donors in good general health, with a Karnofsky or Lansky play performance score > 90%
•DONOR: Donors able to give informed consent (if > 18 years), or with a legal guardian capable of giving informed consent (if < 18 years)

排除标准

•Receiving umbilical cord blood
•With impaired cardiac function as evidenced by ejection fraction < 35% (or, if unable to obtain ejection fraction, shortening fraction of < 26%) or cardiac insufficiency requiring treatment or symptomatic coronary artery disease; patients with a shortening fraction < 26% may be enrolled if approved by a cardiologist
•With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) < 70 mm Hg and carbon monoxide diffusing capability test (DLCO) < 70% of predicted or pO2 < 80 mm Hg and DLCO < 60% of predicted; (or, for pediatric patients unable to perform pulmonary function tests, then oxygen (O2) saturation < 92% on room air), or receiving supplementary continuous oxygen
•With impaired renal function as evidenced by creatinine-clearance < 50% for age, weight, height or serum creatinine > 2 x upper limit of normal or dialysis-dependent
•With hepatic dysfunction as evidenced by total bilirubin > 2.0 x upper limit of normal or evidence of synthetic dysfunction or severe cirrhosis
•With hepatic dysfunction as evidenced by aspartate aminotransferase (AST) > 2.0 x upper limit of normal or evidence of synthetic dysfunction or severe cirrhosis
•With active infectious disease requiring deferral of conditioning, as recommended by an infectious disease specialist
•With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis
•With central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy, cranial irradiation or both prior to initiating conditioning (day -6)
•Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
•With life expectancy severely limited by diseases other than malignancy
•Women who are pregnant or lactating
•With known hypersensitivity to treosulfan or fludarabine (fludarabine phosphate)
•Receiving another experimental drug within 4 weeks before initiation of conditioning (day -6)
•Unable to give informed consent (if > 18 years) or with a legal guardian (if < 18 years) unable to give informed consent
•DONOR: Individuals deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis
•DONOR: Individuals who are HIV-positive
•DONOR: Individuals with active infectious hepatitis
•DONOR: Females with a positive pregnancy test
•DONOR: Persons unable to give informed consent (if > 18 years) or with a legal guardian (if < 18 years) unable to give informed consent