Mature B-Cell Lymphoma And Leukemia Study III
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 128
- 试验地点
- 8
- 主要终点
- Gene Differential Expression Profiling of Burkitt Lymphoma (BL) vs. Non-BL in the US and Other Selected Geographic Regions of the World
研究概览
简要总结
This is a phase III clinical trial using risk-adapted therapy. Treatment outcomes for children with B-cell NHL are excellent. Further improvements in outcome will likely be achieved through more focused study of the biology of the tumors and prospective studies of the late effects of treatment. Toward this end, this study features a spectrum of prospective biologic and late effect studies performed in patients treated with a modified regimen derived from the very successful LMB-96 regimen.
详细描述
- This study will perform analysis of newly diagnosed mature B-cell lymphomas (e.g. Burkitt lymphoma/leukemia, DLBCL, and MLBCL) obtained from participants in different parts of the world.
- This study will describe the types and frequency of mutations in the ARF-HDM2-TP53 pathway, in B-cell lymphomas in the United States and that found in selected geographic regions of the world.
- This study will describe the expression of ARF-HDM2-TP53 and PUMA-associated pathways in B-cell lymphomas in the United States and that found in B-cell lymphomas of other selected geographic regions of the world.
- This study will describe the pattern and frequency of XLP gene mutations presenting with B-cell lymphomas in the United States and selected geographic regions.
- This study will describe the frequency of EBV-positive B-cell lymphomas in the United States and selected geographic regions of the world: and will describe the pattern of EBV protein and gene expression (e.g., EBNA 3) in EBV-positive lymphomas and the study will compare patterns of EBV protein and gene expression with clinical, laboratory and outcome data.
Exploratory Aims:
To estimate the complete response rate, event-free survival, and overall survival rates in patients with Burkitt lymphoma (BL), Burkitt leukemia/B-cell acute leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) treated with a stage-adapted regimen based on the St. Jude B-cell II protocol.
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
- — 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •St. Jude participants and collaborating sites participating in therapeutic and biological objectives:
- •Participant must have a histologic diagnosis of a mature B cell lymphoma (e.g., Burkitt lymphoma/leukemia, atypical Burkitt lymphoma, diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, mature B-cell lymphoma NOS) as defined in the WHO classification.
- •Participant must be previously untreated, (no more than 72 hours of steroids, one intrathecal chemotherapy treatment, and/or emergency radiation).
- •Participant must be < 22 years of age at the time of diagnosis
- •For selected higher-risk CD20+ Group B and all CD20+ Group C participants receiving rituximab only (e.g., those with MLBLC, Stage III with LDH ≥ 2 times upper limit of normal (ULN), and/or bone marrow/CNS involvement: All participants who will receive rituximab must have hepatitis screening prior to enrollment. Participants whose results indicate that they are carrier of hepatitis B can still be treated per Group B or C but will NOT receive rituximab. This screening must be done for eligibility for participants who will receive rituximab, BUT the results are not needed prior to enrollment:
- •Hepatitis B immunization status (vaccination Yes or No)
- •Anti-HBs antibody
- •Anti-HBc antibody.
- •All participants must have screening prior to enrollment; participants whose results indicate that they are carrier of hepatitis B can still be treated per group B and C but will NOT receive rituximab
- •HIV test has been obtained within 42 days. Participants who test positive for HIV cannot be enrolled on therapeutic part of study, but are still eligible for biology studies.
- •Informed consent must be obtained according to St. Jude guidelines before enrollment into study.
- •Participants from Collaborating Sites Participating in Biological Objectives Only:
- •Participant must have a histologic diagnosis of a mature B cell lymphoma (e.g., Burkitt lymphoma/leukemia, atypical Burkitt lymphoma, diffuse large B-cell lymphoma, mediastinal large B-cell lymphoma, mature B-cell lymphoma NOS) as defined in the WHO classification.
- •Participant must be < 22 years of age at the time of diagnosis.
- •Participant must be previously untreated (no more than 72 hours of steroids, one intrathecal chemotherapy treatment, and/or emergency radiation) at the time of the diagnostic biopsy.
- •Informed consent must be obtained by local PI or his/her designee according to ICH/Good Clinical Practice and local guidelines before enrollment into study.
排除标准
- •Participants from Collaborating Sites Participating in Therapeutic and Biological Objectives:
- •Participants known to be HIV positive (for therapeutic part of protocol, HIV participants are eligible for biology studies).
- •Participants who are pregnant or lactating.
- •Inability or unwillingness of research participant or legal guardian to consent.
- •Participants from Collaborating Sites Participating in Biological Objectives Only:
- •Inability or unwillingness of research participant or legal guardian to consent.
- •Histologic diagnosis other than a mature B-cell lymphoma as defined in the WHO classification.
研究组 & 干预措施
Group A
Completely resected stage I or completely resected abdominal stage II lesions.
Group A will include: COPAD x 2 cycles.
干预措施: COPAD (Drug)
Group B
All cases not eligible for Group A or Group C. (Murphy Stage III and non-CNS Stage IV)
Group B will include the intervention COP, COPD M3, CYM as follows:
Pre-Phase: COP
Induction: COPAD M3 x 2 cycles
Consolidation: CYM x 2 cycles.
干预措施: COP, COPD M3, CYM (Drug)
Group C
Any CNS involvement and/or bone marrow involvement ≥ 25% blasts. For CNS involvement one or more of the following applies:
- Any L3 blasts in CSF
- Cranial nerve palsy (if not explained by extracranial tumor)
- Clinical spinal cord compression
- Isolated intracerebral mass
- Parameningeal extension: cranial and/or spinal
Group C will include the intervention COP, COPADM8, CYVE as follows:
Pre-Phase: COP
Induction: COPADM8 cycle 1
Induction: COPADM8 Cycle 2
Consolidation: CYVE x 2 cycles
and Maintenance
干预措施: COP, COPADM8, CYVE (Drug)
结局指标
主要结局
Gene Differential Expression Profiling of Burkitt Lymphoma (BL) vs. Non-BL in the US and Other Selected Geographic Regions of the World
时间窗: 1 year after the participant is enrolled
Gene expression levels in BL vs. non-BL will be analyzed through approximately 22,000 probesets on the Affymetrix U133A GeneChip by using two-factor analysis of variance model for each gene.
Catalog and Estimate Frequencies of Copy Number Variations in Childhood Lymphomas
时间窗: 1 year after the participant is enrolled
The prevalence of CNVs between different subtypes of childhood lymphomas and geographic regions will be reported and compared with exact chi-square or Fisher's test. The CNVs are derived from Affymetrix SNP arrays.
Integrated Analysis of CNVs and Gene Expressions in the US and Other Selected Geographic Regions of the World
时间窗: 1 year after the participant is enrolled
The association between the identified CNVs and gene expressions in the study cohort will be examined by using general linear models, and multiple tests will be considered. Gene expressions are measured by Affymetrix U133A arrays and CNVs are derived from Affymetrix SNP arrays.
Pattern and Frequency of XLP Gene Mutations Presenting With B-cell Lymphomas in the United States and Selected Geographic Regions
时间窗: 1 year after the participant enrollment
Frequency of XLP mutation among boys will be calculated in each geographical region as well as in all regions pooled. The frequency is reported here as the number of boys with XLP gene mutations found in B-cell lymphomas boys.
Frequency of EBV Protein Expression (e.g., EBNA 3) in EBV-positive Lymphomas
时间窗: 1 year after the participant is enrolled
Frequency of EBV-positive BL will be calculated for each geographical region.
次要结局
未报告次要终点