EXTRAMEDULLARY RELAPSE AND OCCULT BONE MARROW INVOLVEMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA: A PHASE III GROUP-WIDE STUDY
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 33
- 主要终点
- Event Free Survival
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
PURPOSE: Phase III trial to compare the effectiveness of combination chemotherapy in treating children who have relapsed acute lymphoblastic leukemia.
详细描述
OBJECTIVES: I. Improve the outcome in children with first isolated central nervous system (CNS), testicular, or ocular relapse of acute lymphoblastic lymphoma (ALL), and increase the knowledge of the characteristics of extramedullary and subsequent relapses of ALL. II. Quantitate, by current molecular biologic techniques, occult systemic leukemia in cases of conventional isolated extramedullary relapse, and examine the relationship between this assessment and subsequent clinical outcome, particularly overt marrow relapse. III. Quantitate occult systemic leukemia in subsets of extramedullary relapse that include site (CNS, testis, or eye), time of relapse (early or late), initial risk group, immunophenotype, DNA index and karyotype, gender (for CNS and eye), and ethnicity, and assess the response to therapy in patients entered on companion protocol CCG-B958. IV. Compare the relative sensitivities of two quantitative in vitro assays for occult systemic leukemia (fluorescence-activated cell sorter/leukemic progenitor cell clonogenic assay vs. polymerase chain reaction-based clonospecific assay), correlate the assays with clinical outcome, and assess other biologic studies of leukemic cells (e.g., neurotropic potential in the SCID mouse xenograft model and methotrexate sensitivity). V. Determine the event-free survival (EFS) and pattern of failure in children with first isolated CNS, testicular, or ocular relapse after treatment that includes intensive systemic chemotherapy. VI. Correlate EFS in patients with CNS and ocular relapse with sex, and in patients with relapse at all three sites with ethnicity. VII. Evaluate the impact of combined chemotherapy and radiotherapy on health status in survivors at two and four years after extramedullary relapse and study entry.
OUTLINE: All patients receive induction chemotherapy over 5 weeks with: etoposide, ifosfamide/mesna, dexamethasone, vincristine, and pegaspargase (if pegaspargase is not available, E. coli asparaginase may be substituted throughout study); then dexamethasone, vincristine, pegaspargase (or E. coli asparaginase), and high-dose methotrexate with leucovorin rescue; and triple intrathecal chemotherapy (TIT). Following induction chemotherapy, all patients receive two 6-week courses of intensification therapy with intermittent TIT; each course consists of dexamethasone, vincristine, high-dose methotrexate/leucovorin, thioguanine, cytarabine, etoposide, and pegaspargase (or E. coli asparaginase) followed by dexamethasone, vincristine, high-dose methotrexate/leucovorin, thioguanine, ifosfamide/mesna, and idarubicin. Patients receive 2 additional courses of intensification chemotherapy followed by four 12-week courses of maintenance chemotherapy with vincristine and methotrexate every 2 weeks and daily oral thioguanine. Total duration of therapy is 78 weeks. Patients with isolated ocular relapse receive local radiotherapy prior to initiation of induction chemotherapy; those who also have CNS leukemia begin TIT with the radiotherapy. Patients with CNS relapse receive craniospinal irradiation during the first month of maintenance therapy, with the dose and fields based on whether they will receive TBI and whether they have had CNS irradiation previously. Patients with testicular relapse receive bilateral testicular irradiation during the first 3 weeks of intensification therapy. Patients are followed every 3 months for 3 years, every 6 months for 3 years, and yearly thereafter, or upon relapse, second malignancy, loss to follow up, or death. All patients undergo quality-of-life assessment at entry and 2 and 4 years after entry.
PROJECTED ACCRUAL: Approximately 120 patients will be accrued for this study.
研究设计
- 研究类型
- Interventional
- 主要目的
- Treatment
入排标准
- 年龄范围
- — 至 20 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: cytarabine (Drug)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: dexamethasone (Drug)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: etoposide (Drug)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: idarubicin (Drug)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: ifosfamide (Drug)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: leucovorin calcium (Drug)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: mesna (Drug)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: pegaspargase (Drug)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: therapeutic hydrocortisone (Drug)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: thioguanine (Drug)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: vincristine sulfate (Drug)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: low-LET electron therapy (Radiation)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: low-LET photon therapy (Radiation)
EARLY # CNS RELAPSE with BM DONOR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, PEG, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, pegaspargase, Ifosfamide with Mesna) and Idarubicin and CXRT.
干预措施: Methotrexate (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: cytarabine (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: dexamethasone (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: etoposide (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: idarubicin (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: ifosfamide (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: leucovorin calcium (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: mesna (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: pegaspargase (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: therapeutic hydrocortisone (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: thioguanine (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: vincristine sulfate (Drug)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: low-LET cobalt-60 gamma ray therapy (Radiation)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: low-LET electron therapy (Radiation)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: low-LET photon therapy (Radiation)
LATE CNS RELAPSE with/without BM DONOR, TESTICULAR or OCULAR
Induction (Etoposide, Ifosfamide with Mesna Uroprotection,Ifosfamide, Dexamethasone, Vincristine sulfate, pegaspargase, ITT (methotrexate, cytosine arabinoside and therapeutic hydrocortisone), and leucovorin calcium then Intensification (4 courses of 6 weeks, ITT, dexamethasone, vincristine, methotrexate, leucovorin, 6-Thioguanine, cytarabine (Ara-C), Etoposide, PEG, Ifosfamide with Mesna) and Idarubicin), and Maintenance (4 x 12 courses) of ITT, Vincristine, Methotrexate, T-thioguanine.
干预措施: Methotrexate (Drug)
结局指标
主要结局
Event Free Survival
The evaluation of the relationship between prognostic or treatment factors and EFS
次要结局
未报告次要终点