A Randomized Phase II Study of Imatinib and Rituximab for Cutaneous Sclerosis After Allogeneic Hematopoietic Cell Transplantation
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 试验地点
- 10
- 主要终点
- Significant Clinical Response
研究概览
简要总结
This randomized phase II trial is evaluating how well imatinib mesylate works compared to rituximab in treating cutaneous sclerosis in patients with chronic graft- versus-host disease (GVHD). Both imatinib and rituximab have been reported to decrease skin thickening and improve skin and joint flexibility in people with cutaneous sclerosis due to chronic GVHD.
详细描述
PRIMARY OBJECTIVES:
I. To determine the best clinical response rate of cutaneous sclerosis (skin and/or fascial thickening) after 6 months of initial therapy with either imatinib (imatinib mesylate) or rituximab.
SECONDARY OBJECTIVES:
I. To determine the best response at either the 3 or 6 month assessment.
II. To determine the response rate at the 3 month assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis within the past 18 months of cutaneous sclerosis after hematopoietic cell transplant (HCT) with sclerotic skin, morphea, myofascial involvement or joint contractures; must have a score of 2 or greater on the Vienna skin scale in any area, or a range-of-motion (ROM) score of 5 or less at the shoulder, elbow or wrist, or 3 or less at the ankle
- •No medication added for the treatment of graft versus host disease (GVHD) within the past 4 weeks
- •Receiving corticosteroids at a dose greater than required for treatment of adrenal insufficiency, unless the physician documents why steroids are contraindicated
- •Age 2-99 years
- •Karnofsky performance status >= 60% at enrollment
- •All females of childbearing potential must have a negative serum or urine pregnancy test =< 7 days prior to starting study therapy
- •All females of childbearing potential must agree to use a form of Food and Drug Administration (FDA) approved contraception from enrollment to one month after study treatment ends
- •Subject has the ability to understand and willingness to sign a written informed consent document
排除标准
- •Total bilirubin > 1.5x upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
- •Renal insufficiency (serum creatinine > 2.0 mg/dl)
- •Platelets < 30,000/ul or absolute neutrophil count < 1500/ul
- •Known hypersensitivity to rituximab or other anti-B cell antibodies
- •Known imatinib intolerance or allergy
- •Evidence of any active viral, bacterial, or fungal infection that is progressive despite appropriate treatment
- •Hepatitis B surface antigen positive
- •Hepatitis B core antibody positive, unless hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable
- •Hepatitis C antibody positive, unless hepatitis C virus (HCV) ribonucleic acid (RNA) is undetectable
- •Pregnant, lactating, or planning a pregnancy while in the study
- •Distal leg skin score 3 or higher as the only manifestation of sclerosis
- •Prior treatment of chronic GVHD with imatinib, rituximab, or any other monoclonal B-cell antibody (e.g. ofatumumab)
- •Receipt of imatinib within the previous 6 months for any indication
- •Receipt of any monoclonal B-cell antibody (e.g. rituximab, ofatumumab) within the previous 12 months for any indication
- •Treatment with anti-B-cell cellular therapy (e.g. chimeric antigen-receptor-engineered cells) at any time after transplant
- •Current treatment with extracorporeal photopheresis (ECP) at the time of enrollment
- •History of psychiatric disorder that would interfere with normal participation in this study
- •Inability or unwillingness of subject and/or parent guardian to provide informed consent or comply with study protocol
- •Use of non-FDA approved drugs within 4 weeks of participation
- •Patient with any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with the study requirements
- •Patients with uncontrolled substance abuse
研究组 & 干预措施
Arm I (enzyme inhibitor)
Patients receive imatinib mesylate PO QD for 6 months in the absence of progression of sclerosis or unacceptable toxicity.
干预措施: imatinib mesylate (Drug)
Arm II (monoclonal antibody)
Patients receive rituximab IV on days 1, 8, 15, and 22. A second treatment cycle is repeated at 3 months for a total of 8 doses of rituximab in the absence of progression of sclerosis or unacceptable toxicity.
干预措施: rituximab (Biological)
结局指标
主要结局
Significant Clinical Response
时间窗: 6 months
Assessed by decline in an affected area's skin score as measured with the Vienna Skin Scale (from 4 \[worst\] to 2, 3 to 1, or 2 to 0 \[best\]) without a concurrent increase of two or more points in another area OR by an increase in the range of motion of the shoulders, elbows or wrists by two points (in a 1-7 scale where 1 is worst and 7 is best) or of the ankles by one point (in a 1 to 4 scale where 1 is worst and 4 is best) without a concurrent worsening in another area.
次要结局
- Patients Who Were Able to Taper Corticosteroids(6 months)
- Baseline Histopathologic Score in the Two Treatment Arms(Enrollment)
- Cumulative Incidence of Treatment Failure(6 months)
- Number of Patients Achieving Improvement in Cutaneous Sclerosis(6 months)
- Percentage of CD27+ B Cells in Responders (SCR) and Non-responders(6 months)
- Patients With Any Percentage Decline in Any Grade of Sclerosis Without Increase in Percentage of Higher Grades of Sclerosis in Other Areas on the Vienna Skin Scale(6 months)
研究者
Lee, Stephanie
Principal Investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium