A Phase II, Multicenter, Open Label Study of Treatment Intensification With ACVD and Brentuximab-Vedotin in Advanced-stage Hodgkin Lymphoma Patients With a Positive Interim PET Scan After 2 ABVD Cycles
试验速览
- 阶段
- 2 期
- 入组人数
- 220
- 试验地点
- 1
- 主要终点
- ]Progression Free Survival (PFS)
研究概览
简要总结
This is a prospective, multi-center, open-label, phase II clinical trial, aims to assess the effectiveness of the combination ACVD (Adriamycin, Cyclophosphamide, Vinblastine and Dacarbazine) and BV (Brentuximab Vedotin) in PET-2 positive advanced-stage HL patients, in order to improve the overall long-term disease control in the entire cohort of advanced-stage HL.
详细描述
With the aim of reducing Blemoycin pulmonary injury (BPI) , Bleomycin was withdrawn and substituted with Cyclophosphamide (ACVD cycle) in patients with a PET-2 negative. All advanced stage HL patients will receive 2 cycles of the standard treatment ABVD and assessed with PET-2 scan.
Knowing that Cyclophosphamide toxicities include cytopenias, amenorrhea and male infertility. These toxicities are mainly dependent on the total cumulative dose. Doses less than 4 g/m2 are not associated with sterility or major toxicity, doses higher than this can lead to azoospermia which was reversible in many cases therefore the cumulative dose will be used in this study is 3200 mg. Additionally, Brentuximab Vedotin has shown significant activity in relapsed refractory HL with minor toxicities.
PET scan after 2 cycles of ABVD has proven to be an excellent tool to identify patients that will have long term PFS of 95% when it is negative and only progression-free survival (PFS) of less than 15% when it is positive.
The primary endpoint of the study will be to assess the overall 3-Y PFS of the entire cohort of patients.
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
- 14 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All the following parameters should be met
- •Newly diagnosed untreated ,histologically proven CD30 positive classical Hodgkin Lymphoma (cHL)
- •Advanced stage (Stage IIB to IVB) as defined by Ann Arbor Staging System (Appendix 1)
- •Age ≥ 14, < 60 years
- •ECOG performance status 0-2
- •Written informed consent for the trial
- •Adequate contraceptive precautions for all patients of childbearing potential
- •All prognostic group
排除标准
- •Any of the following:
- •Pregnant or lactating women.
- •Presence of the following:
- •Heart failure with LVEF <50%
- •Liver enzymes, >2 ULN not attributed to Hodgkin Lymphoma.
- •Another malignancy that is currently clinically significant or requires active intervention
- •Early-stage disease (Stage I- IIA).
- •Patients who are already participating to another clinical trial.
- •Known history of HIV seropositive status
- •ECOG performance status 3-4
- •Creatinin clearance <50 ml/min
- •Prior treatment for Hodgkin Lymphoma excluding steroids
- •Medical or psychiatric conditions compromising the patient's ability to give informed consent
- •Patients with serious active infection
- •Pre-existing peripheral neuropathy (grade 2 or more).
研究组 & 干预措施
Patients with PET-2 Negative Result
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results
PET-2 negative patients will be treated with 4 cycles of ACVD (Adriamycin, Cyclophosphamide, Vinblastine And Dacarbazine)
干预措施: Adriamycin (Drug)
Patients with PET-2 Negative Result
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results
PET-2 negative patients will be treated with 4 cycles of ACVD (Adriamycin, Cyclophosphamide, Vinblastine And Dacarbazine)
干预措施: Cyclophosphamide (Drug)
Patients with PET-2 Negative Result
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results
PET-2 negative patients will be treated with 4 cycles of ACVD (Adriamycin, Cyclophosphamide, Vinblastine And Dacarbazine)
干预措施: Vinblastine (Drug)
Patients with PET-2 Negative Result
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results
PET-2 negative patients will be treated with 4 cycles of ACVD (Adriamycin, Cyclophosphamide, Vinblastine And Dacarbazine)
干预措施: Dacarbazine (Drug)
Patients with PET-2 Negative Result
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results
PET-2 negative patients will be treated with 4 cycles of ACVD (Adriamycin, Cyclophosphamide, Vinblastine And Dacarbazine)
干预措施: ABVD (Drug)
Patients with PET-2 Positive Result
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results
PET-2 positive patients will be treated with 4 cycles of ACVD with addition of Brentuximab Vedotin
干预措施: Adriamycin (Drug)
Patients with PET-2 Positive Result
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results
PET-2 positive patients will be treated with 4 cycles of ACVD with addition of Brentuximab Vedotin
干预措施: Cyclophosphamide (Drug)
Patients with PET-2 Positive Result
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results
PET-2 positive patients will be treated with 4 cycles of ACVD with addition of Brentuximab Vedotin
干预措施: Vinblastine (Drug)
Patients with PET-2 Positive Result
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results
PET-2 positive patients will be treated with 4 cycles of ACVD with addition of Brentuximab Vedotin
干预措施: Dacarbazine (Drug)
Patients with PET-2 Positive Result
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results
PET-2 positive patients will be treated with 4 cycles of ACVD with addition of Brentuximab Vedotin
干预措施: Brentuximab Vedotin (Drug)
Patients with PET-2 Positive Result
After 2 ABVD cycles an interim PET-2 will be performed, and treatment will be adapted according to to PET results
PET-2 positive patients will be treated with 4 cycles of ACVD with addition of Brentuximab Vedotin
干预措施: ABVD (Drug)
结局指标
主要结局
]Progression Free Survival (PFS)
时间窗: 3 years
PFS is estimated from the date of diagnosis until the date of first disease progression or relapse, death for any cause. Superior overall 3 year progression-free survival of patients with PET 2 positive after 2 cycles of ABVD with ACVD and BV compared to historical control of ABVD treated patients and PET 2 negative patients with ACVD only after 2 cycles of ABVD.
次要结局
- Overall Survival (OS)(5 years)