A Phase I/II Dose Escalation Study of Subcutaneous Campath-1H (NSC #715969, IND #10864) During Intensification Therapy in Adults With Untreated Acute Lymphoblastic Leukemia (ALL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 302
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of Alemtuzumab (Phase I)
研究概览
简要总结
This phase I/II trial studies the side effects and best dose of alemtuzumab when given together with combination chemotherapy and to see how well it works in treating patients with untreated acute lymphoblastic leukemia. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy also work in different ways to kill cancer cells or stop them from growing. Giving alemtuzumab together with combination chemotherapy may be a better way to block cancer growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the feasibility and toxicity profiles of escalating doses of Campath-1H (alemtuzumab) given subcutaneously during post-remission intensification treatment of adults with acute lymphoblastic leukemia (ALL).
II. To determine the disease-free survival (DFS) and overall survival (OS) when Campath-1H is used during post-remission intensification treatment of adults with ALL.
III. To determine whether antibody treatment with Campath-1H can further reduce minimal residual disease states in adult ALL.
IV. To obtain preliminary descriptive data on serum levels of Campath-1H during course IV, module D using limited pharmacokinetic sampling during the phase I and II components of the study.
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
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Unequivocal histologic diagnosis of precursor B or precursor T lymphoblastic leukemia (World Health Organization [WHO] classification), L1 or L2 ALL or acute undifferentiated leukemia (AUL) (French-American-British Cooperative group [FAB] Classification); Burkitt-type ALL (FAB L3, surface immunoglobulin [SIg]+) are excluded
- •No prior treatment for leukemia with three permissible exceptions:
- •Emergency leukapheresis II. Emergency treatment for hyperleukocytosis with hydroxyurea III. Cranial radiation therapy (RT) for central nervous system (CNS) leukostasis (one dose only)
- •All patients must have a pre-treatment bone marrow or peripheral blood sample submitted for central immunophenotyping; only those patients who express CD52 >= 10% in the leukemia blast cell channel will be eligible to receive Campath-1H during module D, course IV
排除标准
- 未提供
研究组 & 干预措施
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: vincristine sulfate (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: allopurinol (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: cyclophosphamide (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: daunorubicin hydrochloride (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: dexamethasone (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: asparaginase (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: filgrastim (Biological)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: imatinib mesylate (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: methotrexate (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: cytarabine (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: trimethoprim-sulfamethoxazole (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: mercaptopurine (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: leucovorin calcium (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: alemtuzumab (Biological)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: acyclovir (Drug)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: laboratory biomarker analysis (Other)
Treatment (alemtuzumab and combination chemotherapy)
See detailed description.
干预措施: pharmacological study (Other)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of Alemtuzumab (Phase I)
时间窗: 6 weeks
The maximum tolerated dose is defined as the highest alemtuzumab dose at which less than 40% of patients develop the dose limiting toxicity (DLT), where DLT is defined as the inability to proceed (due to medical complications) with the protocol treatment within six weeks of receiving the last dose of alemtuzumab. Groups of six patients will be enrolled into each cohort at the time of re-registration prior to starting Course IV. After a cohort has accrued 6 patients and at least 3 have completed the 2-6 week post alemtuzumab observation period without DLT, the incoming patients will be assigned to the next cohort in the table while the DLT and other toxicities continue to be assessed for the newly closed cohort. If less than 3 out of 6 enrolled patients in a cohort have completed the 2-6 week post alemtuzumab observation period without DLT, additional patients may continue to enroll in that same cohort, i.e., accrual will not be suspended while waiting for patient follow-up data.
Number of Participants Who Proceed to Course V Within 2-6 Weeks of the Last Dose of Alemtuzumab (Phase II)
时间窗: 8 months
The primary endpoint is the number of participants who are able to proceed to course V within two - six weeks of completion of course IV.
次要结局
- Minimal Residual Disease (MRD) During Treatment With Alemtuzumab (Phase II)(9 years 4 months)
- Disease-free Survival, for Only Complete Response Patients(9 years 4 months)
- Overall Survival(9 years 4 months)