A Non-Randomized Phase III Study of Response Adapted Therapy for the Treatment of Children With Newly Diagnosed High Risk Hodgkin Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 166
- 试验地点
- 177
- 主要终点
- Second-event-free Survival
研究概览
简要总结
This phase III trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed Hodgkin lymphoma. 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. Radiation therapy uses high energy x-rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To maintain the overall survival (as defined by 4-year "second-event" free survival) for subjects with high risk Hodgkin lymphoma at or above 95%.
SECONDARY OBJECTIVES:
I. To maintain 3-year event-free survival for subjects with high risk Hodgkin lymphoma at or above 93%.
II. To maintain comparable overall survival (as defined by 4-year "second-event" free survival) between subjects with high risk Hodgkin lymphoma who have a rapid or slow response to the initial 2 cycles of ABVE-PC* by intensifying therapy through the addition of 2 cycles of ifosfamide/vinorelbine in those with a slow early response.
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
- •Pathologically confirmed newly diagnosed Hodgkin lymphoma (HL) meeting one of the following criteria:
- •Classical disease
- •Nodular lymphocyte-predominant disease
- •Stage III or IV disease with B symptoms, as defined by ≥ 1 of the following:
- •Unexplained weight loss > 10% within the past 6 months
- •Unexplained recurrent fever > 38°C within the past month
- •Recurrent drenching night sweats within the past month
- •Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:
- •0.4 mg/dL (1 to 5 months)
- •0.5 mg/dL (6 to 11 months)
- •0.6 mg/dL (12 to 23 months)
- •0.8 mg/dL (2 to 5 years)
- •1 mg/dL (6 to 9 years)
- •1.2 mg/dL (10 to 12 years)
- •1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years)
- •1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years)
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
- •AST or ALT < 2.5 times ULN for age
- •Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 50% by MUGA (unless due to large mediastinal mass from HL)
- •FEV_1/FVC > 60% by pulmonary function tests (PFT) (unless due to large mediastinal mass fromHL)
- •For children who are unable to cooperate for PFTs, the criteria are:
- •No evidence of dyspnea at rest
- •No exercise intolerance
- •Pulse oximetry > 92% on room air
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No pathologic prolongation of QTc interval (> 450 milliseconds) on 12-lead ECG
- •No prior chemotherapy, biological response modifiers (e.g., monoclonal antibody therapy), or radiotherapy
- •At least 28 days since prior corticosteroids except for emergent treatment for respiratory distress or spinal cord compression, or for treatment of allergy to contrast agent required for CT scan
- •No other concurrent cancer chemotherapy or immunomodulating agents (including steroids)
- •Concurrent corticosteroid therapy as treatment or prophylaxis for anaphylactic reactions allowed
- •No concurrent pegfilgrastim
排除标准
- 未提供
研究组 & 干预措施
Regimen I (consolidation therapy)
Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
干预措施: bleomycin sulfate (Biological)
Regimen I (consolidation therapy)
Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
干预措施: doxorubicin hydrochloride (Drug)
Regimen I (consolidation therapy)
Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
干预措施: liposomal vincristine sulfate (Drug)
Regimen I (consolidation therapy)
Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
干预措施: cyclophosphamide (Drug)
Regimen I (consolidation therapy)
Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
干预措施: etoposide phosphate (Drug)
Regimen I (consolidation therapy)
Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
干预措施: prednisone (Drug)
Regimen I (consolidation therapy)
Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.
干预措施: filgrastim (Biological)
Regimen II (consolidation therapy)
Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
干预措施: bleomycin sulfate (Biological)
Regimen II (consolidation therapy)
Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
干预措施: doxorubicin hydrochloride (Drug)
Regimen II (consolidation therapy)
Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
干预措施: liposomal vincristine sulfate (Drug)
Regimen II (consolidation therapy)
Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
干预措施: vinorelbine tartrate (Drug)
Regimen II (consolidation therapy)
Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
干预措施: cyclophosphamide (Drug)
Regimen II (consolidation therapy)
Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
干预措施: etoposide phosphate (Drug)
Regimen II (consolidation therapy)
Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
干预措施: prednisone (Drug)
Regimen II (consolidation therapy)
Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
干预措施: filgrastim (Biological)
Regimen II (consolidation therapy)
Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.
干预措施: ifosfamide (Drug)
Induction: all patient
All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease.
干预措施: doxorubicin hydrochloride (Drug)
Induction: all patient
All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease.
干预措施: liposomal vincristine sulfate (Drug)
Induction: all patient
All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease.
干预措施: cyclophosphamide (Drug)
Induction: all patient
All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease.
干预措施: etoposide phosphate (Drug)
Induction: all patient
All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease.
干预措施: prednisone (Drug)
Induction: all patient
All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease.
干预措施: filgrastim (Biological)
结局指标
主要结局
Second-event-free Survival
时间窗: At 4 years from enrollment
Second event here is defined as any relapse/progression of Hodgkin Lymphoma (HL) or a previously reported second malignant neoplasm (SMN), a new SMN, or death after a first event which can be relapse/progression of HL, SMN, biopsy-proven HL following completion of Consolidation for Slow Early Response (SER) patient, positive bilateral bone marrow biopsy following completion of Consolidation for Stage IV patient, or death. If death occurs as the 1st event, it also counts as the 2nd event.
Safety Analysis and Monitoring of Toxic Death
时间窗: Within 30 days of protocol treatment at median follow-up of 48 months (range: 1 to 70 months).
The primary endpoint for safety analysis and monitoring is toxic death, which is death primarily attributable to treatment.
次要结局
- Event Free Survival(At 3 years from enrollment)
- Second-event-free Survival(At 4 years from enrollment)
- Event-free Survival for Rapid Early Response (RER) Positron Emission Tomography(PET)-1 Positive, RER PET-1 Negative(3 years from enrollment)
- Relapse-free Survival(3 years from enrollment)
- Grade 3 and 4 Non-hematologic Toxicities During Protocol Therapy(During and after completion of study treatment.)
- Overall Survival(At 3 years from enrollment)