A Phase III Study to Determine Efficacy and Safety of Low-Dose Glucocorticoids for Initial Treatment of Acute Graft-versus-Host Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 164
- 试验地点
- 1
- 主要终点
- Mean Cumulative Prednisone Dose (mg/kg) Over 42 Days From the Start of Treatment
研究概览
简要总结
This randomized phase III trial is studying low-dose prednisone or methylprednisolone to see how well they work compared with standard-dose prednisone or methylprednisolone in treating patients with newly diagnosed acute graft-versus-host disease (GVHD). Glucocorticoids, such as prednisone or methylprednisolone at a starting dose of 2 mg/kg/day are standard treatment for acute graft-versus-host disease caused by a donor stem cell transplant. It is not yet known whether low-dose glucocorticoids are more effective than standard-dose glucocorticoids in treating acute graft-versus-host-disease
详细描述
OBJECTIVES:
I. To determine whether a lower starting dose of prednisone for treatment of newly diagnosed acute GVHD results in decreased prednisone exposure without compromising overall survival.
II. To estimate the magnitude of clinical benefit associated with the reduction in prednisone exposure.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I (Low-dose; prednisone-equivalent dose at initiation of treatment of 0.5 mg/kg/day or 1.0 mg/kg/day; stratified according to initial symptom severity): Patients receive low-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with newly diagnosed acute GVHD (>= grade IIa) for whom, in the judgment of the attending physician, initial treatment with systemic glucocorticoids is indicated
- •Patient or guardian able and willing to provide informed consent
排除标准
- •Hallmarks of chronic GVHD
- •GVHD after donor lymphocyte infusion (DLI)
- •Patient unwilling to remain in Seattle under the care of the Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA) through day 42 after the start of treatment for GVHD
- •Uncontrolled infection or other underlying comorbidity (i.e. severe psychiatric illness) that precludes the use of "standard-dose" prednisone
- •Recent diagnosis of recurrent or progressive malignancy that precludes the use of "standard-dose" prednisone
- •Any prior systemic therapy for acute GVHD (Patients may receive up to 2 doses of low-dose prednisone prior to randomization; low-dose prednisone is defined as 0.5 mg/kg/dose for patients who present with grade IIa GVHD and 1 mg/kg/dose for those who present with grade IIb-IV GVHD)
- •Enrollment on Blood and Marrow Transplant Clinical Trials Network (BMT-CTN) trial 0802
研究组 & 干预措施
Arm I (Low-dose)
Patients receive low-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
干预措施: prednisone (Drug)
Arm I (Low-dose)
Patients receive low-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
干预措施: methylprednisolone (Drug)
Arm I (Low-dose)
Patients receive low-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
干预措施: questionnaire administration (Other)
Arm II (Standard-dose)
Patients receive standard-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
干预措施: prednisone (Drug)
Arm II (Standard-dose)
Patients receive standard-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
干预措施: methylprednisolone (Drug)
Arm II (Standard-dose)
Patients receive standard-dose prednisone or methylprednisolone once or twice daily in the absence of disease progression or unacceptable toxicity.
干预措施: questionnaire administration (Other)
结局指标
主要结局
Mean Cumulative Prednisone Dose (mg/kg) Over 42 Days From the Start of Treatment
时间窗: At day 42 after initiation of treatment
The total cumulative dose of prednisone (milligrams/kilogram) was calculated starting from the start of therapy through study day 42.
次要结局
- Prednisone-associated Toxicity as Assessed by Invasive Infections (Bacterial, Fungal and Viral)(Baseline and through 100 days of treatment)
- Prednisone-associated Toxicity as Assessed by Hyperglycemia(Baseline and then through 42 days after starting treatment)
- Prednisone-associated Toxicity as Assessed by Myopathy(Baseline and then weekly until 42 days after starting treatment)
- Prednisone-associated Toxicity as Assessed by Hypertension(Baseline and then through 42 days after starting treatment)
- Prednisone-associated Toxicity as Assessed by Quality of Life(Baseline and then every other week until 42 days after starting treatment)
- Non-relapse Mortality(At 12 months after the start of prednisone therapy)
- Recurrent or Progressive Malignancy(At 12 months after the start of prednisone therapy)
- Progression to Grade III-IV Acute GVHD(At approximately 100 days after transplant)
- Secondary Therapy for Acute GVHD Beyond Prednisone(At approximately 100 days after transplant)
- Chronic Extensive GVHD(At 12 months after the start of prednisone therapy)
- Overall Survival(At 12 months after the start of prednisone therapy)
研究者
Marco Mielcarek
Principal Investigator
Fred Hutchinson Cancer Center