Phase II Study of the Efficacy and Toxicity of Campath-1H in the Therapy of Adult T-Cell Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 2
- 主要终点
- Overall Response Rate
研究概览
简要总结
This study will examine the safety and effectiveness of Alemtuzumab (Campath-1H) for treating patients with adult T-cell leukemia/lymphoma (ATL). ATL is caused by a virus called human T-cell lymphotrophic virus type-1 (HTLV-1) that infects lymphocytes (white blood cells) called T-cells. Cancerous cells can be found not only in the blood, but also in the skin, lungs, lymph nodes, liver, bone, bone marrow, spleen, and meninges (tissues covering the brain). There are four categories of ATL, based on the aggressiveness of disease-smoldering, chronic, lymphoma, and acute. Campath-1H is a monoclonal antibody that attaches to and kills normal and cancerous lymphocytes, including T cells. Although Campath-1H is an experimental drug for treating ATL, it is approved by the Food and Drug Administration for treating chronic lymphocytic leukemia.
Patients 18 years of age and older with any type of ATL except smoldering may be eligible for this study. Candidates are screened with a medical history and physical examination, photos of skin lesions, measurement of lesions such as lymph nodes and skin nodules, blood and urine tests, electrocardiogram (EKG), chest x-ray, computed tomography (CT) scan or ultrasound of the abdomen, skin biopsy, bone marrow aspirate and biopsy, skin test, and lumbar puncture (spinal tap). Participants undergo treatment in two phases, as follows:
- Dose escalation phase: Patients receive an infusion of Campath-1H daily for three days. The initial dose is low and is increased daily as long as there are no side effects, or only mild reactions, until the patient is receiving the maximum dose of 30 milligrams per day.
- Stable dose phase: Patients receive infusions of Campath-1H 30 mg three times a week for up to 12 weeks.
In addition to treatment, patients are evaluated with the following tests and procedures:
- History and physical examination every 4 weeks.
- Blood tests every 4 weeks.
- CT scans to measure the size of the tumors every 4 weeks.
- Skin biopsies (if skin disease is present) and lymph note aspirates: Up to five biopsies and five aspirates may be taken to help diagnose the disease and evaluate the effect of Campath-1H on the cancer.
- Bone marrow biopsy: This procedure may be done to document or monitor disease progress.
Patients receive treatment for up to 12 weeks. Treatment may stop earlier if the patient achieves a complete response before the end of 12 weeks. Patients completing the study are followed periodically with a history and physical examination, blood and urine tests, tumor evaluation, skin biopsy and skin testing. They are seen monthly at first and then at 3-month intervals the first year; every 4 months the second year, every 6 months for the third through fifth years, and then yearly.
详细描述
Background:
Adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoproliferative disorder caused by an infection with the human T-cell lymphotrophic virus type-1 (HTLV-1).
ATL is characterized by rapidly rising peripheral blood leukemia cell counts, lymphadenopathy, lytic bone lesions, hepatosplenomegaly, and skin and solid organ involvement by tumor.
Chemotherapy has shown modest activity and the treatment of ATL has remained largely undefined and the survival of ATL patients poor.
The CD52 surface glycoantigen is overexpressed on ATL cells.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have serum antibodies directed to Human T-lymphotropic Virus Type 1 (HTLV-1).
- •All patients must have a histologically confirmed diagnosis of adult T- cell leukemia/lymphoma and more than 10% of the malignant cells must express CD52 and CD
- •All stages of Tac-expressing adult T-cell leukemia except smoldering are eligible: patients with chronic, lymphoma or acute Acute T-cell leukemia/lymphoma (ATL) are eligible.
- •Patients must have measurable disease. All patients with greater than 10% abnormal (i.e. Tac homogeneous strongly expressing) peripheral blood mononuclear cell (PBMC)in the peripheral blood will be deemed to have measurable disease.
- •The patient must have a granulocyte count of at least 100/mm(3) and a platelet count of greater than or equal to 50,000/mm(3).
- •Patients must have a creatinine of less than 3.0 mg/dl.
- •Omission of cytotoxic chemotherapy for ATL for 3 weeks prior to entry into the trial is required. However patients receiving a stable dose of corticosteroids for at least three to four weeks without evidence of tumor response will be eligible.
- •Patients must have a life expectancy of greater than 2 months.
- •Eligible patients must be greater than or equal to 18 years old. There is no upper age limit.
- •Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) value less than or equal to 2.5-fold greater than the upper limit of normal and bilirubin less than or equal to 3.0/dl. If a liver function test is judged to be elevated due to the underlying ATL, this parameter will be considered an unevaluable parameter for toxicity determinations.
- •Patients must be able to understand and sign an Informed Consent form.
- •All patients must use adequate contraception during participation in this trial and for three months after completing therapy.
排除标准
- •Patients with symptomatic leukemic meningitis will be excluded. However patients that have both ATL and another HTLV-1-associated disease, tropical spastic paraparesis (TSP) will be included.
- •Pregnant and nursing patients are not eligible for the study. Because the effects of CAMPATH-1H on the developing fetus are unknown pregnant women will be excluded. Breast-feeding in patients with HTLV-1 infection is contraindicated because of the risk of transmission of the virus to the child. In addition, CAMPATH-1H may be present in breast milk and produce adverse events in the breast-feeding child.
- •Human immunodeficiency virus (HIV) positive patients are excluded from the study. CAMPATH-1H may produce a different pattern of toxicities in patients with HIV infection and in addition the depletion of T cells produced by CAMPATH-1H may have adverse effects on HIV positive individuals.
- •Patients with smoldering ATL are excluded.
- •Patients with previously received Campath-1GH are ineligible.
结局指标
主要结局
Overall Response Rate
时间窗: 60 months
Overall response rate is defined as the percentage of participants with response and utilizes the International Standardized workshop definition. Complete response(CR)-Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy and normalization of those biochemical abnormalities (for example LDH) definitely assignable to the lymphoma. Please see the protocol Link module for the full criteria if desired.
Overall Survival
时间窗: 60 months
Time between the first day of treatment to the day of death.
Time to Progression
时间窗: 60 months
Time between the first day of treatment to the day of disease progression which is defined as a persistent (at least two determinations) doubling of the peripheral blood leukemic cell count, the development of new lesions, or Ca elevations that are uncontrolled by conventional therapeutic procedures.
次要结局
- Cell Surface Expression of CD52 on Tumor Cells(6 months)
- The Number of Participants With Adverse Events(18 months)