A Phase II Pilot Trial of Bortezomib (PS-341, Velcade) in Combination With Intensive Re-Induction Therapy for Children With Relapsed Acute Lymphoblastic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 148
- 试验地点
- 171
- 主要终点
- Severe Adverse Events (SAE) Rate.
研究概览
简要总结
This pilot, phase II trial studies the side effects of giving bortezomib together with combination chemotherapy and to see how well it works in treating young patients with relapsed acute lymphoblastic leukemia or lymphoblastic lymphoma. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with combination chemotherapy may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To estimate the toxicity, second complete response (CR2) rate at the end of Block 1 therapy, and 4-month event-free survival (EFS) for pediatric and young adult patients with relapsed acute lymphoblastic leukemia (ALL) treated with bortezomib in combination with intensive re-induction chemotherapy.
II. To evaluate bortezomib pharmacokinetics (PK) in patients receiving the combination regimen.
SECONDARY OBJECTIVES:
I. To assess minimal residual disease (MRD) in bone marrow following completion of each therapy block.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 31 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis
- •Pre-B ALL in first early (< 36 months from diagnosis) isolated bone marrow (BM) or combined BM/extramedullary relapse; or
- •T-cell ALL in first isolated BM or combined relapse; or
- •T-LL in first relapse
- •Patients with leukemia must have had histologic verification of the malignancy at relapse, including immunophenotyping to confirm diagnosis
- •Patients with lymphoblastic lymphoma must have measurable disease documented by clinical, radiographic, or histologic criteria; patients must have relapsed or become refractory to conventional therapy
- •Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
- •Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study
- •Patients who relapse on therapy other than standard ALL maintenance therapy must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- •At least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy
- •At least 7 days since the completion of therapy with a biologic agent or donor lymphocyte infusions (DLI); for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
- •No evidence of active graft-vs-host disease (GVHD) and >= 4 months must have elapsed; must not be receiving GVHD prophylaxis
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- •1 month to < 6 months (0.4 male, 0.4 female)
- •6 months to < 1 year (0.5 male, 0.5 female)
- •1 to < 2 years (0.6 male, 0.6 female)
- •2 to < 6 years (0.8 male, 0.8 female)
- •6 to < 10 years (1 male, 1 female)
- •10 to < 13 years (1.2 male, 1.2 female)
- •13 to < 16 years (1.5 male, 1.4 female)
- •>= 16 years (1.7 male, 1.4 female)
- •Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
- •Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3 x ULN for age, unless elevation due to leukemia infiltration
- •Shortening fraction of >= 27% by echocardiogram, or
- •Ejection fraction of >= 50% by gated radionuclide study
- •No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >= 94% at sea level (> 90% if at high altitude)
- •No evidence of acute pulmonary infiltrates on chest radiograph
- •Patients with seizure disorder may be enrolled if on allowed anticonvulsants and well controlled; benzodiazepines and gabapentin are acceptable
- •Central nervous system (CNS) toxicity =< grade 2
- •Peripheral nervous system (PNS) toxicity < grade 3
- •All patients and/or their parents or legal guardians must sign a written informed consent
- •All institutional, FDA, and National Cancer Institute (NCI) requirements for human studies must be met
排除标准
- •Patients with Philadelphia chromosome positive ALL are not eligible unless refractory to at least one tyrosine kinase inhibitor (TKI) therapy; patients that are unable to tolerate TKI therapy due to toxicity are eligible
- •Patients with mature B-cell ALL, ie, leukemia with B-cell (soluble immunoglobulin [sIg] positive and kappa or lambda restricted positivity) ALL, with French-American-British (FAB) L3 morphology and/or a myc translocation, are not eligible
- •Extramedullary disease status: patients with isolated CNS disease or isolated testicular disease are not eligible
- •Patients with known optic nerve and/or retinal involvement are not eligible; patients presenting with visual disturbances should have an ophthalmological exam and, if indicated, an magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement
- •Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome are not eligible
- •Cumulative prior anthracycline exposure must not exceed 400 mg/m^2
- •Patients taking anticonvulsants known to activate the cytochrome p450 system, in particular anticonvulsants such as phenytoin, carbamazepine, and phenobarbital, are not eligible; benzodiazepines and gabapentin are acceptable
- •Patients who have previously received bortezomib or other proteasome inhibitors are not eligible
- •Patients who have a known allergy to doxorubicin, cytarabine, both etoposide and etopophos, boron, mannitol or bortezomib are not eligible
- •Patients who cannot receive any asparaginase products (E. Coli, PEG-asparaginase, or Erwinia asparaginase) on this study (eg, due to prior severe pancreatitis, stroke or other toxicity) are not eligible; patients who initially receive asparaginase, but must discontinue due to toxicity, remain eligible; patients with clinically significant prior allergies to pegaspargase are eligible if Erwinia L-asparaginase can be substituted
- •Patients who are pregnant or breast-feeding are not eligible for this study; negative pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective birth control method
- •Patients must not have received any prior re-induction attempts and must not have received treatment for prior extramedullary relapse; patients with primary induction failure are not eligible
研究组 & 干预措施
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: L-asparaginase (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: doxorubicin hydrochloride (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: therapeutic hydrocortisone (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: vincristine sulfate (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: cytarabine (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: prednisone (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: bortezomib (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: pegaspargase (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: methotrexate (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: etoposide phosphate (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: cyclophosphamide (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: filgrastim (Biological)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: leucovorin calcium (Drug)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: laboratory biomarker analysis (Other)
Pre-B ALL Relapse<18 mths from diagnosis (chemo) age<=21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: High Dose MTX (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: L-asparaginase (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: doxorubicin hydrochloride (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: therapeutic hydrocortisone (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: vincristine sulfate (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: cytarabine (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: prednisone (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: bortezomib (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: pegaspargase (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: methotrexate (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: etoposide phosphate (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: cyclophosphamide (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: filgrastim (Biological)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: leucovorin calcium (Drug)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: laboratory biomarker analysis (Other)
Pre-B ALL Relapse 18-36 mths from diagnosis (chemo) age<=21 yr
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: High Dose MTX (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: L-asparaginase (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: doxorubicin hydrochloride (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: therapeutic hydrocortisone (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: cyclophosphamide (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: vincristine sulfate (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: cytarabine (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: prednisone (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: bortezomib (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: pegaspargase (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: methotrexate (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: etoposide phosphate (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: cyclophosphamide (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: filgrastim (Biological)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: leucovorin calcium (Drug)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: laboratory biomarker analysis (Other)
Pre-B ALL Relapse<36 mths from diagnosis (chemo) age>21 yrs
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: High Dose MTX (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: L-asparaginase (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: doxorubicin hydrochloride (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: therapeutic hydrocortisone (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: vincristine sulfate (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: cytarabine (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: prednisone (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: bortezomib (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: pegaspargase (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: methotrexate (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: etoposide phosphate (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: filgrastim (Biological)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: leucovorin calcium (Drug)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: laboratory biomarker analysis (Other)
T-cell ALL (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: High Dose MTX (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: L-asparaginase (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: doxorubicin hydrochloride (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: therapeutic hydrocortisone (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: vincristine sulfate (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: cytarabine (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: prednisone (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: bortezomib (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: pegaspargase (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: methotrexate (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: etoposide phosphate (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: cyclophosphamide (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: filgrastim (Biological)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: leucovorin calcium (Drug)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: laboratory biomarker analysis (Other)
T-cell Lymphoblastic Lymphoma (LL) (Chemotherapy)
Re-Induction Block 1 patients receive vincristine sulfate, Prednisone, pegaspargase, Doxorubicin hydrochloride. Re-Induction Block 2 patients receive Cyclophosphamide, Etoposide phosphate, and Methotrexate. Re-Induction Block 3 patients receive Cytarabine.
干预措施: High Dose MTX (Drug)
结局指标
主要结局
Severe Adverse Events (SAE) Rate.
时间窗: 4 months
The proportion of SAE rate among all eligible patients
Second Complete Remission Rate at the End of Block 1 Reinduction Chemotherapy
时间窗: The outcome is measured the end of Block 1 (Day 36 of Block 1) of re-induction therapy.
The percentage of eligible and evaluable patients who have achieved complete response at the end Block 1 of re-induction therapy.
Event Free Survival
时间窗: 4 months after enrollment
Percentage of patients who were event free at 4 months
Toxic Death Rate
时间窗: 4 months
The proportion of toxic death rate among all eligible patients.
次要结局
- Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 1(End of Block 1 (Day 36 of Block 1) of re-induction therapy)
- Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 2(End of Block 2 (Day 36 of Block 2) of re-induction therapy)
- Rate of Minimal Residual Disease (MRD) < 0.01% at End Block 3(End of Block 3 (Day 36 of Block 3) of re-induction therapy)