Prospective Randomized Comparison of ABVD Versus BEACOPP Chemotherapy With or Without Radiotherapy for Advanced Stage or Unfavorable Hodgkin's Lymphoma (HL)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 331
- 试验地点
- 1
- 主要终点
- Freedom from first progression at 5 years
研究概览
简要总结
The choice of a preferred first-line treatment requires balancing the desire for optimal disease control with the occurrence of early and late treatment-related effects. To fully assess this balance, the treatment decision process should ideally take into account the outcome following a consistent second-line therapy, in particular when tolerated, widely applicable and highly effective salvage regimens exist, like in Hodgkin lymphoma failing initial chemotherapy.
详细描述
During the last two decades ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) has been considered as the standard of care for advanced HL, however 20-30% of the patients fail to achieve a durable complete remission and need a salvage treatment. After a state-of-the art-salvage program including high-dose chemotherapy and autologous hematopoietic stem cell support (ASCT) at least half of these patients achieve a durable disease control. Recently the German Hodgkin Study Group (GHSG) has developed a new regimen, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone), administered with or without dose escalation. In an interim analysis after 23 months follow-up, BEACOPP demonstrated a higher activity compared to COPP/ABVD with a superior freedom from treatment failure (84% versus 75%, P=.034). Despite the improved efficacy a substantial proportion of patients receiving escalated BEACOPP experienced severe acute hematologic toxicity (grade 3-4 leucopoenia, thrombocytopenia and anemia occurred in 78% , 36% and 27% of the cycles administered, respectively) and 1.8% fatal acute toxicities were reported. Moreover of greater concern is the incidence of almost fatal secondary acute leukemia and myelodysplastic syndrome (3 cases in 323 patients). The choice of first-line treatment requires balancing the desire for optimal disease control with the occurrence of early and late treatment-related toxicities. Long-term outcome following an optimal salvage treatment, consisting in high-dose chemotherapy with ASCT should also be taken into consideration. In the present study we plan to compare the efficacy and toxicity of two therapeutic strategies consisting in two different first-line treatments followed by a pre-planned salvage program, when indicated
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 17 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed, newly diagnosed Hodgkin's lymphoma (pathological review diagnosis available)
- •No prior treatment
- •Stage II B, III A and B, IV A and B
- •Normal hematopoietic function as measured by leucocytes equal to or greater than 3500/mm3, neutrophils equal to or greater than 1500/mm3, platelets equal to or greater than 100000/mm3
- •Normal renal function (serum creatinine < 1,5x ULN) and normal liver function (SGOT/SGPT equal to or lower than 2.5x ULN; bilirubin equal to or lower than 1.5x ULN)
- •No significant history or current evidence of cardiovascular disease, or major respiratory disease
- •No severe neurologic or psychiatric disease
- •No other malignancy except basal cell carcinoma of the skin and/or in situ cervical carcinoma of the uterus
- •Serological negativity for hepatitis B or C or HIV infection
- •ECOG performance status equal to or lower than 2
- •Life expectancy of at least three months
- •Effective contraception in all patients and a negative pregnancy test for women of childbearing potential
- •Written informed consent and consent to a regular follow-up in the outpatient clinic
- •Exclusion criteria:
- •Sever central nervous system or psychiatric disease
- •History or current evidence of clinically significant cardiac disease (congestive heart failure, uncontrolled hypertension, unstable coronary artery disease or myocardial infarction or severe arrhythmias. Left ventricular ejection fraction < 50% at rest by echocardiography or < 55% by isotopic measurement
- •Serological positivity for HBV, HCV or HIV
- •History or current evidence of malignancy other than basal cell carcinoma of the skin, carcinoma in situ of the cervix
- •Lactating or pregnant women
排除标准
- 未提供
研究组 & 干预措施
Arm B
BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles
干预措施: Bleomycin (Drug)
Arm B
BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles
干预措施: Etoposide (Drug)
Arm B
BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles
干预措施: Doxorubicin (Drug)
Arm A
ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 to 8 cycles
干预措施: Dacarbazine (Drug)
Arm B
BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles
干预措施: Cyclophosphamide (Drug)
Arm B
BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles
干预措施: Vincristine (Drug)
Arm B
BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles
干预措施: Procarbazine (Drug)
Arm B
BEACOPP (Bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) for 4 escalated cycles followed by 4 standard cycles
干预措施: Prednisone (Drug)
Arm A
ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 to 8 cycles
干预措施: Doxorubicin (Drug)
Arm A
ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 to 8 cycles
干预措施: Bleomycin (Drug)
Arm A
ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for 6 to 8 cycles
干预措施: Vinblastine (Drug)
结局指标
主要结局
Freedom from first progression at 5 years
时间窗: After a median of 5 years from start of the study
次要结局
- Number of participants long term sequelae(After a median of 10 years)
- Number of participants with acute adverse events at initial therapy and at salvage therapy as a measure of safety and tolerability(After 3 months from last intervention)
- Freedom from second progression at 5 years(After a median of 5 years from start of protocol)
- Overall survival at 5 years(After a median of 5 years from start of the protocol)