A Pilot Study To Determine The Toxicity Of The Addition Of Rituximab To The Induction And Consolidation Phases And The Addition Of Rasburicase To The Reduction Phase In Children With Newly Diagnosed Advanced B-Cell Leukemia/Lymphoma Treated With LMB/FAB Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 97
- 试验地点
- 1
- 主要终点
- Grade ≥ 3 Stomatitis
研究概览
简要总结
Phase II trial to study the effectiveness of combining rituximab and rasburicase with combination chemotherapy in treating young patients who have newly diagnosed advanced B-cell leukemia or lymphoma. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug with rituximab may kill more cancer cells. Chemoprotective drugs such as rasburicase may protect kidney cells from the side effects of chemotherapy.
详细描述
OBJECTIVES:
I. Determine the toxicity of the addition of rituximab to induction chemotherapy comprising vincristine, methylprednisolone, methotrexate, leucovorin calcium, cyclophosphamide, and doxorubicin (COPADM) [COMRAP] and to consolidation chemotherapy in children with newly diagnosed FAB prognostic group B or group C leukemia or lymphoma treated with LMB/FAB therapy.
II. Determine the toxicity of the addition of rasburicase to the reduction phase comprising cyclophosphamide, vincristine, prednisone or methylprednisolone, methotrexate, and leucovorin calcium (COP-R) in these patients.
III. Determine the incidence of tumor lysis syndrome, renal complications, and the use of assisted renal support (i.e., dialysis or hemofiltration) during the COP-R reduction phase and the first induction phase of COPADM or COMRAP in these patients.
IV. Determine the response rate of patients treated with COMRAP incorporated into LMB/FAB therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 29 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed mature B-lineage (CD20-positive) leukemia or lymphoma by the REAL classification of 1 of the following subtypes:
- •Diffuse large cell lymphoma
- •Burkitt's lymphoma
- •High-grade B-cell lymphoma (Burkitt-like)
- •No B-cell anaplastic large cell Ki-1 positive lymphomas and B-lymphoblastic lymphomas
- •One of the following FAB prognostic groups:
- •Group B (intermediate risk)
- •Group C (high risk)
- •Bone marrow involvement with at least 25% blasts and/or CNS involvement meeting 1 or more of the following criteria:
- •Any L3 blasts in cerebrospinal fluid
- •Cranial nerve palsy (if not explained by extracranial tumor)
- •Clinical spinal cord compression
- •Isolated intracerebral mass
- •Parameningeal extension (cranial and/or spinal)
- •Hepatitis B status known
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception during and for 6 months after study participation
- •No known history of congenital immune deficiency and/or laboratory evidence of acquired immune deficiency
- •No known G6PD deficiency (if receiving rasburicase)
- •No prior malignancies treated with systemic chemotherapy with alkylator or anthracycline therapy
- •No prior chemotherapy
- •At least 1 week since prior steroids except emergency steroids initiated within 72 hours of study entry
- •No prior radiotherapy except emergency radiotherapy initiated within 72 hours of study entry
- •No concurrent radiotherapy
- •No prior solid organ transplantation
排除标准
- 未提供
研究组 & 干预措施
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: doxorubicin hydrochloride (Drug)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: cyclophosphamide (Drug)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: methotrexate (Drug)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: rasburicase (Drug)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: leucovorin calcium (Drug)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: prednisone (Drug)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: methylprednisolone (Drug)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: filgrastim (Biological)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: rituximab (Biological)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: cytarabine (Drug)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: vincristine sulfate (Drug)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: hydrocortisone sodium succinate (Drug)
Group B (chemotherapy, protective therapy, monoclonal antib.)
Therapies given IV, IT, orally, or SC. Please see treatment outline. See Detailed Description.
干预措施: laboratory biomarker analysis (Other)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: doxorubicin hydrochloride (Drug)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: cyclophosphamide (Drug)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: methotrexate (Drug)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: leucovorin calcium (Drug)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: prednisone (Drug)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: methylprednisolone (Drug)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: filgrastim (Biological)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: rituximab (Biological)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: cytarabine (Drug)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: etoposide (Drug)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: vincristine sulfate (Drug)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: hydrocortisone sodium succinate (Drug)
Group C (Chemotherapy, monoclonal antibody therapy)
Therapies given IV, IT, orally, or subcutaneously (same as FAB B with the addition of etoposide and high-dose methotrexate). See Detailed Description.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Grade ≥ 3 Stomatitis
时间窗: Up to 1 year
The incidence of grade ≥ 3 stomatitis. Grade 3 stomatitis: Confluent ulcerations or pseudomembranes; bleeding with minor trauma. Grade 4 stomatitis: Tissue necrosis; Significant spontaneous bleeding; life-threatening consequences
Minimal Residual Disease
时间窗: Not Provided
The presence or absence of tumor cells at the end of induction assessed by studying tissue and/or blood/marrow. Details of methods and criteria used can be found in Shiramizu at al. BJH 153:758-763, 2011 (full citation in the citation section).
Toxic Death
时间窗: Up to 1 year
Implementation of the toxic death rate stopping rule, a death must be possibly, probably or definitely attributable to Rituximab and/or chemotherapy to be considered a toxic death.
Response Rate
时间窗: Up to 5 years
Response includes both complete and partial responses. Per protocol, complete Response is defined as the complete disappearance of all clinical evidence of disease by physical examination, by imaging studies, by bone marrow biopsy (where indicated), by CNS evaluation (where indicated) and by biopsy where there is a residual abnormality on an imaging study. Bone marrow must contain \<5% blasts. CSF WBC must be \<5/μL with no blasts or lymphomatous cells present. Partial response is defined as: at least a 50% reduction in the size of all measurable tumor areas. Each site is to be defined by the product of the maximum length, width and depth (3 dimensions). No lesion may progress. No new lesion may appear. Bone marrow must contain \<5% blasts. CSF WBC must be \<5/μL with no blasts or lymphomatous cells present..
次要结局
未报告次要终点