A Randomized Study on CNS Prophylaxis With Liposome-Encapsulated Cytarabine in Association With a Lineage-Targeted and MRD-Oriented Postremission Strategy in Adult ALL
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 145
- 试验地点
- 16
- 主要终点
- Comparative analysis of feasibility/toxicity of IT DepoCyte vs. TIT
研究概览
简要总结
The aim of this clinical study in adult ALL is to compare by risk category (1) the feasibility of two different CNS prophylaxis regimens and (2) the overall disease-free survival in relation to the achievement of an early MRD negative status and following consolidation with lineage-targeted methotrexate infusions and other disease-specific therapeutic elements, with or without the application of allogeneic or autologous SCT depending on risk class and MRD study results.
In this multicentric prospective pilot randomized phase II trial on CNS prophylaxis, all patients receive induction/consolidation therapy incorporating lineage-targeted high-dose methotrexate plus other drugs (with additional imatinib in Ph/BCR-ABL+ ALL), for the achievement of an early negative MRD status. The MRD study supports a risk/MRD-oriented final consolidation phase.
详细描述
A) Risk Classification
Newly diagnosed patients are hierarchically clustered into very high, high and standard risk cases (VHR, HR, SR) using international risk criteria modified according to NILG:
A1) VHR (any criterium): B-precursor: WBC count >100x109/L; adverse cytogenetics/molecular biology such as t(9;22)/BCR-ABL, t(4;11)/MLL rearrangement at 11q23, +8, -7, del6q, t(8;14), low hypodiploidy with 30-39 chromosomes, near triploidy with 60-78 chromosomes, complex with >5 unrelated anomalies. T-precursor: WBC count >100x109/L; early/late non-cortical immunophenotype (CD1a-); adverse cytogenetics/molecular biology (as above).
A2) HR (any criterium, VHR excluded): B-precursor: WBC count >30x109/L; pro-B immunophenotype; complete remission after cycle 2. T-precursor: complete remission after cycle 2.
A3) SR (all criteria, VHR/HR excluded): B-precursor: WBC count <30x109/L; T-precursor: WBC count <100x109/L; cortical immunophenotype (CD1a+).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years.
- •Diagnosis of untreated ALL with B-/T-precursor phenotype or B-cell lymphoblastic lymphoma (B-LL), either de novo or secondary to chemo-radiotherapy for other cancer.
- •Full cytological, cytochemical, cytogenetic and immunobiological disease characterization by revised FAB, EGIL and WHO criteria.
- •Bone marrow and peripheral blood sampling (ALL) or biopsy specimen (LL) for MRD study.
- •ECOG performance status 0-2 or reversible ECOG 3 score following intensive care of complications.
- •Signed informed consent.
排除标准
- •Diagnosis of B-ALL (FAB L3 ALL/Burkitt's leukemia or lymphoma) and T-LL (T-cell lymphoblastic lymphoma).
- •Down's syndrome.
- •Pre-existing, uncontrolled pathology such as cardiac disease (congestive/ischemic, acute myocardial infarction within the past 3 months, untreatable arrythmias, NYHA classes III and IV), severe liver disease with serum bilirubin >3 mg/dL and/or ALT >3 x upper normal limit (unless attributable to ALL/LL), kidney function impairment with serum creatinine >2 mg/dL (unless attributable to ALL/LL), and severe neurological or psychiatric disorder that impairs the patient's ability to understand and sign the informed consent, or to cope with the intended treatment plan.
- •Known HIV positive serology.
- •Other active hematological or non-hematological cancer with life expectancy <1 year.
- •Pregnancy (fertile women will be advised not to become pregnant while on treatment; and male patients to adopt contraceptive methods), unless therapeutic aborption/early discharge is carried out.
研究组 & 干预措施
Intrathecal DepoCyte
I.t. DepoCyte 50 mg admninistered x6-8 (depending on immunophenotypic disease subset) during induction/consolidation/eraly maintenance phases
干预措施: liposome-encapsulated cytarabine (DepoCyte) (Drug)
Triple intrathecal therapy (TIT)
Methotrexate 12,5 mg + Cytarabine 50 mg + Prednisolone 40 mg injected intrathecally x12 during indiction/consolidation phases
干预措施: Triple intrathecal therapy (TIT) (Drug)
结局指标
主要结局
Comparative analysis of feasibility/toxicity of IT DepoCyte vs. TIT
时间窗: weeks 5, 11, 17 and 23
次要结局
- Overall survival(Study follow-up)
- Comparative analysis of isolated and combined CNS recurrence following TIT vs DepoCyte prophylaxis(During study follow-up)
- Complete remission (CR)(After study chemotherapy cycles 1 and 2)
- Bone marrow MRD negativity rates(Four time-points at weeks 4-22)
- Lenght of remission(Study follow-up)
研究者
DR RENATO BASSAN
Medical Doctor
Northern Italy Leukemia Group