A Randomised Phase III Trial With a PET Response Adapted Design Comparing ABVD +/- ISRT With A2VD +/- ISRT in Patients With Previously Untreated Stage IA/IIA Hodgkin Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,042
- 试验地点
- 128
- 主要终点
- Progression free survival (PFS)
研究概览
简要总结
RADAR is a multicentre, international, randomised, open-label phase III clinical trial composed of 2 trials running in parallel. Trial 1 will be led and sponsored by University College London (UCL) and conducted in Europe and Australia/New Zealand. Trial 2 will be led by the Canadian Cancer Trials Group (CCTG) and conducted in North America, with CCTG the regulatory sponsor in Canada, and University of Miami the regulatory sponsor and IND holder in the US. Datasets from Trial 1 and Trial 2 will be combined to achieve the total sample size. Data analysis will be performed by UCL and therefore UCL is responsible for the clinicaltrials.gov entry.
Eligible patients will be randomised to receive either ABVD or A2VD chemotherapy.
An interim PET-CT scan will be performed after 2 cycles of treatment, which will be used to adapt subsequent treatment. Patients will receive a total of 3-4 cycles of chemotherapy and may also receive involved site radiotherapy as consolidation.
Patients will be followed up for a minimum of 5 years after treatment.
详细描述
Eligible patients will be randomised to receive either ABVD chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine) or A2VD chemotherapy (doxorubicin, brentuximab vedotin, vinblastine and dacarbazine, with growth factor support).
If patients agree, they will have a PET-CT scan after 1 cycle (PET1). The result of this scan will be blinded and used for exploratory endpoints only. Treatment will not be influenced by the result of this scan.
All patients will have a PET-CT scan after 2 cycles of treatment (PET2) which will be centrally reviewed. The Deauville score from central review will be used to risk adapt subsequent therapy as follows:
- Patients with Deauville score 1-3 will have one further cycle of their randomised chemotherapy and then enter follow up.
- Patients with Deauville score 4 will have two further cycles of their randomised chemotherapy followed by involved site radiotherapy
- Patients with Deauville score 5 will be withdrawn from trial treatment. They will have further treatment at their treating clinician's discretion and will enter follow up for the trial.
Patients with Deauville score 4 on PET2 will have a final PET-CT scan to confirm adequate treatment response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 69 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females aged 16-69 years (inclusive) (age range is 18-69 in US and EU)
- •Histologically confirmed classical Hodgkin lymphoma
- •Stage I or II supradiaphragmatic disease with no mediastinal bulk disease (defined as greater than a third of the transthoracic diameter at any level of thoracic vertebra as determined by CT) or B symptoms. Bulky disease at other sites is acceptable. Extranodal disease (single extranodal site (stage I) or contiguous nodal extension (stage II)) is acceptable.
- •ECOG performance status 0-
- •No previous treatment for Hodgkin lymphoma
- •Fit to receive anthracycline-based chemotherapy (patients with a history of ischaemic heart disease or hypertension should have a left ventricular ejection fraction of ≥50%)
- •Creatinine clearance (measured or calculated >40ml/min
- •Total bilirubin <1.5 x upper limit of normal, unless attributable to disease or known Gilbert's syndrome
- •ALT or AST < 2 x upper limit of normal
- •Adequate bone marrow function with neutrophils ≥1.0x10^9/l and platelets ≥100x10^9/l
- •Haemoglobin ≥8g/dL
- •Willing and able to comply with the requirements of the protocol, including contraceptive advice, where applicable
- •Written informed consent
排除标准
- •Previous treatment for Hodgkin lymphoma, excluding short courses of oral corticosteroids at a dose of 100mg prednisolone (or equivalent) for up to 7 days
- •Infradiaphragmatic disease
- •Nodular lymphocyte predominant Hodgkin lymphoma
- •Absence of FDG-avid lesions on baseline PET scan
- •Age 70 years or over or age 15 years or under
- •Other cancer diagnosed with the last 5 years. Patients with completely excised carcinoma in situ of any type and basal or squamous cell carcinoma of the skin are not excluded
- •Recurrent or persistent other cancer within last 5 years irrespective of date of initial diagnosis
- •Pre-existing grade ≥1 sensory or motor neuropathy from any cause
- •History of or current progressive multi-focal leukoencephalopathy or other chronic condition of the brain
- •Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
- •Infection with HIV, hepatitis C or active hepatitis B infection (surface antigen or DNA positive)
- •Any active systemic viral, bacterial or fungal infection requiring systemic antibiotics, antivirals or antifungals within 2 weeks prior to first trial drug dose
- •Receiving or recently treated with any other investigational agent (within 4 weeks of trial entry)
- •Pregnant or breastfeeding women
- •Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of ABVD
- •Known history of any cardiovascular or respiratory conditions that would preclude anthracycline or bleomycin administration
- •Other significant medical or psychiatric comorbidity that in the opinion of the investigator would make administration of ABVD or A2VD hazardous
研究组 & 干预措施
ABVD +/- ISRT
2 x 28 day cycles of ABVD: Doxorubicin 25mg/m^2 IV days 1 & 15 Bleomycin 10000 IU/m^2 days 1 & 15 Vinblastine 6mg/m^2 days 1 & 15 Dacarbazine 375mg/m^2 days 1 & 15
PET-CT after 2 cycles will determine subsequent treatment:
Deauville score 1-3 (PET CMR): 1 further cycle of ABVD then follow up Deauville score 4 (PET positive): 2 further cycles of ABVD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.
干预措施: Dacarbazine (Drug)
A2VD +/- ISRT
2 x 28 day cycles of A2VD: Doxorubicin 25mg/m^2 IV days 1 & 15 Brentuximab vedotin 1.2mg/kg (max 120mg) days 1 & 15 Vinblastine 6mg/m^2 days 1 & 15 Dacarbazine 375mg/m^2 days 1 & 15 Filgrastim (or equivalent haematopoietic growth factor) for 5-7 days from day 2 and day 16 (or single dose of peg-filgrastim on days 2 & 16)
PET-CT after 2 cycles will determine subsequent treatment:
Deauville score 1-3 (PET CMR): 1 further cycle of A2VD then follow up Deauville score 4 (PET positive): 2 further cycles of A2VD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.
干预措施: Haematopoietic growth factor (Drug)
ABVD +/- ISRT
2 x 28 day cycles of ABVD: Doxorubicin 25mg/m^2 IV days 1 & 15 Bleomycin 10000 IU/m^2 days 1 & 15 Vinblastine 6mg/m^2 days 1 & 15 Dacarbazine 375mg/m^2 days 1 & 15
PET-CT after 2 cycles will determine subsequent treatment:
Deauville score 1-3 (PET CMR): 1 further cycle of ABVD then follow up Deauville score 4 (PET positive): 2 further cycles of ABVD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.
干预措施: Bleomycin (Drug)
ABVD +/- ISRT
2 x 28 day cycles of ABVD: Doxorubicin 25mg/m^2 IV days 1 & 15 Bleomycin 10000 IU/m^2 days 1 & 15 Vinblastine 6mg/m^2 days 1 & 15 Dacarbazine 375mg/m^2 days 1 & 15
PET-CT after 2 cycles will determine subsequent treatment:
Deauville score 1-3 (PET CMR): 1 further cycle of ABVD then follow up Deauville score 4 (PET positive): 2 further cycles of ABVD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.
干预措施: Vinblastine (Drug)
ABVD +/- ISRT
2 x 28 day cycles of ABVD: Doxorubicin 25mg/m^2 IV days 1 & 15 Bleomycin 10000 IU/m^2 days 1 & 15 Vinblastine 6mg/m^2 days 1 & 15 Dacarbazine 375mg/m^2 days 1 & 15
PET-CT after 2 cycles will determine subsequent treatment:
Deauville score 1-3 (PET CMR): 1 further cycle of ABVD then follow up Deauville score 4 (PET positive): 2 further cycles of ABVD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.
干预措施: Doxorubicin (Drug)
ABVD +/- ISRT
2 x 28 day cycles of ABVD: Doxorubicin 25mg/m^2 IV days 1 & 15 Bleomycin 10000 IU/m^2 days 1 & 15 Vinblastine 6mg/m^2 days 1 & 15 Dacarbazine 375mg/m^2 days 1 & 15
PET-CT after 2 cycles will determine subsequent treatment:
Deauville score 1-3 (PET CMR): 1 further cycle of ABVD then follow up Deauville score 4 (PET positive): 2 further cycles of ABVD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.
干预措施: Involved site radiotherapy (Radiation)
A2VD +/- ISRT
2 x 28 day cycles of A2VD: Doxorubicin 25mg/m^2 IV days 1 & 15 Brentuximab vedotin 1.2mg/kg (max 120mg) days 1 & 15 Vinblastine 6mg/m^2 days 1 & 15 Dacarbazine 375mg/m^2 days 1 & 15 Filgrastim (or equivalent haematopoietic growth factor) for 5-7 days from day 2 and day 16 (or single dose of peg-filgrastim on days 2 & 16)
PET-CT after 2 cycles will determine subsequent treatment:
Deauville score 1-3 (PET CMR): 1 further cycle of A2VD then follow up Deauville score 4 (PET positive): 2 further cycles of A2VD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.
干预措施: Doxorubicin (Drug)
A2VD +/- ISRT
2 x 28 day cycles of A2VD: Doxorubicin 25mg/m^2 IV days 1 & 15 Brentuximab vedotin 1.2mg/kg (max 120mg) days 1 & 15 Vinblastine 6mg/m^2 days 1 & 15 Dacarbazine 375mg/m^2 days 1 & 15 Filgrastim (or equivalent haematopoietic growth factor) for 5-7 days from day 2 and day 16 (or single dose of peg-filgrastim on days 2 & 16)
PET-CT after 2 cycles will determine subsequent treatment:
Deauville score 1-3 (PET CMR): 1 further cycle of A2VD then follow up Deauville score 4 (PET positive): 2 further cycles of A2VD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.
干预措施: Dacarbazine (Drug)
A2VD +/- ISRT
2 x 28 day cycles of A2VD: Doxorubicin 25mg/m^2 IV days 1 & 15 Brentuximab vedotin 1.2mg/kg (max 120mg) days 1 & 15 Vinblastine 6mg/m^2 days 1 & 15 Dacarbazine 375mg/m^2 days 1 & 15 Filgrastim (or equivalent haematopoietic growth factor) for 5-7 days from day 2 and day 16 (or single dose of peg-filgrastim on days 2 & 16)
PET-CT after 2 cycles will determine subsequent treatment:
Deauville score 1-3 (PET CMR): 1 further cycle of A2VD then follow up Deauville score 4 (PET positive): 2 further cycles of A2VD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.
干预措施: Involved site radiotherapy (Radiation)
A2VD +/- ISRT
2 x 28 day cycles of A2VD: Doxorubicin 25mg/m^2 IV days 1 & 15 Brentuximab vedotin 1.2mg/kg (max 120mg) days 1 & 15 Vinblastine 6mg/m^2 days 1 & 15 Dacarbazine 375mg/m^2 days 1 & 15 Filgrastim (or equivalent haematopoietic growth factor) for 5-7 days from day 2 and day 16 (or single dose of peg-filgrastim on days 2 & 16)
PET-CT after 2 cycles will determine subsequent treatment:
Deauville score 1-3 (PET CMR): 1 further cycle of A2VD then follow up Deauville score 4 (PET positive): 2 further cycles of A2VD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.
干预措施: Brentuximab vedotin (Drug)
A2VD +/- ISRT
2 x 28 day cycles of A2VD: Doxorubicin 25mg/m^2 IV days 1 & 15 Brentuximab vedotin 1.2mg/kg (max 120mg) days 1 & 15 Vinblastine 6mg/m^2 days 1 & 15 Dacarbazine 375mg/m^2 days 1 & 15 Filgrastim (or equivalent haematopoietic growth factor) for 5-7 days from day 2 and day 16 (or single dose of peg-filgrastim on days 2 & 16)
PET-CT after 2 cycles will determine subsequent treatment:
Deauville score 1-3 (PET CMR): 1 further cycle of A2VD then follow up Deauville score 4 (PET positive): 2 further cycles of A2VD followed by involved site radiotherapy (ISRT) Deauville score 5: withdraw from trial treatment; further treatment will be given at the treating clinician's discretion. Enter follow up for the trial.
干预措施: Vinblastine (Drug)
结局指标
主要结局
Progression free survival (PFS)
时间窗: 3 years from end of treatment
Time from randomisation to first date of progression or death
次要结局
- PET-CMR (complete metabolic response) rate(At the end of cycle 2 (each cycle is 28 days))
- Overall survival (OS)(5 years from end of treatment)
- Incidence of second cancers and cardiovascular disease(5 years from end of treatment)
- Event-free survival (EFS)(5 years from end of treatment)
- Safety and toxicity of ABVD and A2VD as described by CTCAE v5.0(From start of treatment to 30 days post treatment)