Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation (ADAPT)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This is a prospective, single-arm, phase II study. Patients will be treated with an allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body irradiation (TBI) conditioning with different melphalan and TBI doses based on patient- and disease-related risk.
详细描述
Eligible patients will receive an allogeneic stem cell transplantation using a combination of fludarabine, melphalan and total body irradiation (TBI) conditioning regimen and post-transplant high dose cyclophosphamide (PTCY), tacrolimus and mycophenolate mofetil (MMF) for graft-versus-host prophylaxis.
Melphalan and TBI doses will be tailored based on the Hematopoietic Stem Cell Transplant- Composite Risk (HCT-CR), age and Karnofski performance status (KPS). Melphalan dose ranges from 100 -140 mg/m2 while TBI dose ranges from 2-5 Gy.
All patients will be monitored for safety and efficacy up to 2 years post-transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 18-70 years
- •Diagnosis of AML, ALL, MDS, CML, NHL, HD, CLL requiring AHSCT
- •Has an HLA-matched related (MRD), HLA-matched unrelated (MUD), haploidentical (HAPLO) or 1-Ag mismatched unrelated donor (MMUD)
- •Karnofsky performance >70%
- •Adequate major organ system function as demonstrated by:
- •Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockroft-Gault formula).
- •Bilirubin equal or less than 1.5 mg/dl except for Gilbert's disease. ALT or AST equal or less than 200 IU/ml for adults. Conjugated (direct) bilirubin less than 2x upper limit of normal.
- •Left ventricular ejection fraction equal or greater than 40%.
- •Diffusing capacity for carbon monoxide (DLCO) equal or greater than 50% predicted corrected for hemoglobin.
- •Ability to understand and the willingness to sign a written informed consent. a. Both men and women and members of all races and ethnic groups are eligible for this trial. Non-English speaking, deaf, hard of hearing and illiterate individuals are eligible for this trial.
排除标准
- •Inability to comply with medical recommendations or follow-up
- •Active/uncontrolled bacterial or viral infection (PI is the final arbiter of this criterion.)
- •Has active CNS or ocular disease involvement within 3 months
- •Patients with primary CNS lymphoma
- •Patients who require modifications of the conditional regimen
研究组 & 干预措施
Patients with AML, ALL, MDS, CML, NHL, HD, CLL requiring AHSCT
Patients will be treated with allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body irradiation (TBI) conditioning with different melphalan and TBI doses based on their Hematopoietic Cell Transplant - Composite Risk (HCT-CR), age, and Karnofski performance status (KPS).
干预措施: Fludarabine (Drug)
Patients with AML, ALL, MDS, CML, NHL, HD, CLL requiring AHSCT
Patients will be treated with allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body irradiation (TBI) conditioning with different melphalan and TBI doses based on their Hematopoietic Cell Transplant - Composite Risk (HCT-CR), age, and Karnofski performance status (KPS).
干预措施: Melphalan (Drug)
Patients with AML, ALL, MDS, CML, NHL, HD, CLL requiring AHSCT
Patients will be treated with allogeneic stem cell transplantation (AHSCT) using fludarabine, melphalan and total body irradiation (TBI) conditioning with different melphalan and TBI doses based on their Hematopoietic Cell Transplant - Composite Risk (HCT-CR), age, and Karnofski performance status (KPS).
干预措施: Total Body Irradiation (Radiation)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: Up to 48 months
PFS is defined as the time from stem cell infusion to time of disease relapse or death from any cause; data for patients who were alive without relapse will be censored at the date of last contact.
次要结局
- Overall survival (OS)(Up to 48 months)
- Cumulative incidence of Graft-Versus-Host-Free, relapse-free survival (GRFS)(Up to 48 months)
- Cumulative incidence of relapse(Up to 48 months)
- Cumulative incidence of Non-Relapse Mortality (NRM)(Up to 48 months)
- Cumulative incidence of acute and chronic graft versus host disease (GVHD)(Up to 48 months)
- Area Under the Curve (AUC) of Melphalan(From melphalan infusion start time to 22 hours after the infusion.)
研究者
Stefan Octavian Ciurea
Professor of Clinical Medicine
University of California, Irvine