Ma-Spore ALL-Seq 2020: RNA-Seq and IgH/TCR-Seq to Improve Risk Assignment in Childhood, Adolescent and Young Adult Acute Lymphoblastic Leukaemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 3
- 主要终点
- Overall survival (OS)
研究概览
简要总结
The primary objective of this trial is to improve the overall survival rate of children and young adult with B-lineage acute lymphoblastic leukemia (B-ALL) in Singapore and Malaysia in the context of a multicenter cooperative trial using a risk-stratified therapy.
详细描述
This is a multicenter open-label phase II study involving children and young adult (< 41 years old) who are newly diagnosed with B-ALL and treatment naïve. There will be 3 parallel cohorts whose risk to be stratified based upon leukemia genetics profiles and patient's treatment response:
- Standard Risk (SR)
- Intermediate Risk (IR)
- High Risk (HR)
All drugs being used are commercially available chemotherapy drugs. There will be no novel chemotherapeutic agent without marketing authorization being tested in this trial.
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 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has been diagnosed with B-lineage ALL as evidenced by:
- •BMA blasts > 20% AND
- •Leukemic process in the bone marrow, peripheral blood or any extra medullary tissue with confirmation of B-lymphoid differentiation by flow immunophenotyping or histopathologically
- •Age < 41 years of age at enrolment
- •Written informed consent obtained from patient or legally acceptable representative (LAR)
排除标准
- •T-lineage ALL
- •Down syndrome with ALL
- •History of previous malignancies or this ALL is a second malignancy
- •Mixed phenotype acute leukemia (MPAL) or undifferentiated leukemia
- •Mature B-cell leukemia/lymphoma
- •Any previous cytotoxic therapy (chemotherapy/radiotherapy/immunotherapy). Patient pre-treated with short term steroid (< 7 days of duration within last 1 month prior to ALL treatment start) may be enrolled after discussion and written approval from PI. These patients should be treated on at least intermediate arm.
- •Persistent renal dysfunction with creatinine more than upper limit of normal for age before start of induction therapy. Patients requiring temporary dialysis without persistent renal dysfunction can qualify.
- •Liver dysfunction with direct bilirubin > 10x upper normal limit for age.
- •Any serious uncontrolled medical condition or impending end organ dysfunction that would impair the ability of the subject to receive protocol therapy
- •Doubtful compliance or ability to complete study therapy due to financial, social, familial or geographic reason, or in the judgement of site investigator
研究组 & 干预措施
Standard risk (SR)
- No anthracycline throughout the treatment.
- CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4
干预措施: Prednisolone (Drug)
Standard risk (SR)
- No anthracycline throughout the treatment.
- CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4
干预措施: Dexamethasone (Drug)
Standard risk (SR)
- No anthracycline throughout the treatment.
- CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4
干预措施: Vincristine (Drug)
Standard risk (SR)
- No anthracycline throughout the treatment.
- CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4
干预措施: Methotrexate (Drug)
Standard risk (SR)
- No anthracycline throughout the treatment.
- CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4
干预措施: L-Asparaginase (Drug)
Standard risk (SR)
- No anthracycline throughout the treatment.
- CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4
干预措施: Pegylated asparaginase (Drug)
Standard risk (SR)
- No anthracycline throughout the treatment.
- CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4
干预措施: Erwinase (Drug)
Standard risk (SR)
- No anthracycline throughout the treatment.
- CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4
干预措施: Cyclophosphamide (Drug)
Standard risk (SR)
- No anthracycline throughout the treatment.
- CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4
干预措施: Cytarabine (Drug)
Standard risk (SR)
- No anthracycline throughout the treatment.
- CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4
干预措施: Mercaptopurine (Drug)
Standard risk (SR)
- No anthracycline throughout the treatment.
- CNS consolidation using "Capizzi type" low dose methotrexate (LDMTX) x 2 courses to replace pre-existing high dose methotrexate (HDMTX) 2.5g #3/4
干预措施: Thioguanine (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Prednisolone (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Dexamethasone (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Vincristine (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Methotrexate (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: L-Asparaginase (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Imatinib (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Pegylated asparaginase (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Erwinase (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Thioguanine (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Cyclophosphamide (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Cyclophosphamide (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Cytarabine (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Mercaptopurine (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Rituximab (Drug)
Intermediate risk (IR)
Those with CD20 ≥ 20% expression on diagnostic blasts by flow immunophenotyping will receive additional dose of rituximab on day 1 of each delayed intensification (DI) phases: phase III (2 courses) and V (1 course) for total 3 infusions
干预措施: Doxorubicin (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Prednisolone (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Dexamethasone (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Vincristine (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Methotrexate (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: L-Asparaginase (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Pegylated asparaginase (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Erwinase (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Dasatinib (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Cytarabine (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Mercaptopurine (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Thioguanine (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Doxorubicin (Drug)
High risk (HR)
Provisional HR patients will be offered CAR-T cell immunotherapy or HSCT
干预措施: Fludarabine (Drug)
结局指标
主要结局
Overall survival (OS)
时间窗: 5 years from diagnosis
OS is calculated from the date of diagnosis to the date of last follow-up or any death
次要结局
- Event free survival (EFS)(5 years from diagnosis)