A Phase II Clinical Trial to Evaluate the Safety and Efficacy of Sirolimus for Secondary Treatment of Chronic Graft-versus-Host Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Number of Participants Experiencing Treatment Success
研究概览
简要总结
This phase II trial studies the side effects and how well sirolimus works as secondary therapy in treating patients with chronic graft-versus-host disease (GVHD) that did not respond to prior treatment. Sirolimus may be an effective treatment for chronic GVHD
详细描述
PRIMARY OBJECTIVES:
I. To assess the safety of sirolimus administered at a dose which provides steady-state, whole blood trough levels of 5-10 ng/mL in patients with chronic GVHD.
II. To determine whether administration of sirolimus provides benefit for patients with chronic GVHD that has not responded adequately to previous systemic treatment.
OUTLINE:
Patients receive sirolimus orally (PO) once daily (QD). Patients continue to receive prednisone and cyclosporine or tacrolimus at the discretion of the managing physician.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Biopsy-confirmed diagnosis of clinical extensive chronic GVHD with inadequate response to previous treatment and where secondary systemic therapy is indicated because of
- •Clinical progression of signs and symptoms of chronic GVHD in a previously involved organ, or
- •Development of signs and symptoms of chronic GVHD in a previously uninvolved organ, or
- •Absence of improvement after 3 months of primary treatment, or
- •Continued need for treatment with prednisone at doses >= 1.0 mg/kg/day for more than 2 months, without qualification for type of donor, graft or conditioning regimen
- •Patient or guardian able and willing to provide informed consent
- •Stated willingness to use contraception in women of child-bearing potential (Food and Drug Administration [FDA] requirement)
- •Stated willingness of the patient to comply with study procedures and reporting requirements
- •Stated willingness of the physician most involved in management of chronic GVHD (the "managing physician,") to comply with study procedures and reporting requirements
排除标准
- •Fungal or viral infection with no radiographic evidence of improvement during continued appropriate antimicrobial therapy
- •Cytomegalovirus (CMV) antigenemia unresponsive to antiviral therapy
- •Active disseminated varicella zoster virus (VZV) infection with persistent non-crusted lesions
- •Inability to tolerate oral medications
- •Absolute neutrophil count (ANC) < 1500/uL
- •Platelet count < 50,000/uL
- •Persistent or recurrent malignancy, including histopathologic evidence of myeloma or lymphoma; patients with breakpoint cluster region-abelson (bcr/abl) detected by polymerase chain reaction (PCR) assay as the only evidence of persistent chronic myeloid leukemia may be enrolled
- •Pregnancy
- •Known history of hypersensitivity to sirolimus
研究组 & 干预措施
Sirolimus
Study participants receive sirolimus added once daily to their baseline combination therapy of prednisone plus either cyclosporine or tacrolimus at the discretion of the managing physician. Treatment other than cyclosporine (or tacrolimus) and prednisone must be discontinued when administration of sirolimus is started. Topical therapy, including psoralen and UVA irradiation (PUVA), glucocorticoid creams, topical tacrolimus, oral beclomethasone, topical azathioprine and ophthalmic glucocorticoids may be given at the discretion of the managing physician in consultation with the transplant center.
干预措施: sirolimus (Drug)
结局指标
主要结局
Number of Participants Experiencing Treatment Success
时间窗: Approximately 7 years
Defined as the absence of any immunosuppressive treatment, including sirolimus, with resolution of all reversible manifestations of chronic GVHD and no additional systemic therapy.
Number of Participants Experiencing Treatment Failure
时间窗: Approximately 7 years
Defined as the initiation of additional systemic therapy, development of bronchiolitis obliterans, or death from causes other than recurrent malignancy during primary treatment for chronic GVHD, whichever occurs first.
Number of Participants Needing Additional Systemic Therapy
时间窗: Approximately 7 years
Includes any intervention intended to control chronic GVHD through an immunosuppressive effect from oral or parenteral administration of any systemic medication not originally given under auspices of this protocol.
Number of Participants With Recurrent Malignancy
时间窗: Approximately 7 years
Defined as clinical or histopathologic evidence demonstrating the presence of any malignancy considered as the indication for transplant. Recurrent malignancy will also be defined as any post-transplant intervention not routinely used to prevent the development of overt recurrence, prompted by laboratory evidence of persisting malignant cells but without clinical or histopathologic evidence of recurrence.
次要结局
- Proportion of Patients Who Discontinue Administration of Sirolimus Because of Toxicity(Approximately 7 years)
- Proportion With Infections Categorized by Organism(Approximately 7 years)
- Secondary Malignancies(Up to 7 years)
- Duration of Treatment With Prednisone(Approximately 7 years)
- Probability of Survival Without Recurrent Malignancy(Approximately 7 years)
- Probability of Overall Survival(Approximately 7 years)
- Probability of Cumulative Incidence of Death Without Recurrent Malignancy(Approximately 7 years)
- Probability of Cumulative Incidence of Recurrent Malignancy(Approximately 7 years)
研究者
Paul Carpenter
Principal Investigator
Fred Hutchinson Cancer Center