RADAR: 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
ESTADO CLÍNICO
Reclutando
FASE/S DEL ENSAYO
Fase III
PATOLOGÍA
Coagulopatías hemorrágicas, Leucemia linfática crónica y otros SLPC, Linfoma Hodgkin, Trasplante de progenitores hematopoyéticos, Linfoma
FECHA DE APERTURA
Julio, 2023
FECHA DE CIERRE
,
CRITERIOS DE INCLUSIÓN
Males and females age 16-69 years (inclusive).
Adequate bone marrow function with neutrophils 1.0x10exp9/l and platelets 100 x10exp9/l
Haemoglobin 80 g/L (equivalent to 4.96mmol/L)
Willing and able to comply with the requirements of the protocol, including contraceptive advice, where applicable
Written informed consent
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 vertebrae as determined by CT) or B symptoms. Bulky disease at other sites is acceptable. Extranodal disease (single extranodal site (stage I) or contiguous extranodal extension (stage II)) is acceptable.
ECOG performance status 0-2
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) >40 ml/min
Total bilirubin < 1.5 x upper limit of normal, unless attributable to disease or known Gilberts syndrome
ALT or AST < 2 x the upper limit of normal
Adequate bone marrow function with neutrophils 1.0x10exp9/l and platelets 100 x10exp9/l
Haemoglobin 80 g/L (equivalent to 4.96mmol/L)
Willing and able to comply with the requirements of the protocol, including contraceptive advice, where applicable
Written informed consent
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 vertebrae as determined by CT) or B symptoms. Bulky disease at other sites is acceptable. Extranodal disease (single extranodal site (stage I) or contiguous extranodal extension (stage II)) is acceptable.
ECOG performance status 0-2
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) >40 ml/min
Total bilirubin < 1.5 x upper limit of normal, unless attributable to disease or known Gilberts syndrome
ALT or AST < 2 x the upper limit of normal
CRITERIOS DE EXCLUSIÓN
Previous treatment for Hodgkin lymphoma, excluding short courses of oral corticosteroids at a dose of up to 100mg prednisolone (or equivalent) for up to 7 days
Nodular lymphocyte predominant Hodgkin lymphoma
Absence of FDG-avid lymphoma lesions on baseline PET scan
Age 70 years or over, or 17 years and under
Other active cancer (new, relapsed or persistent) within the last 5 years with the exception of: a) Prostate cancer meeting the following criteria: Gleason grade group 1 (Gleason score 6) being managed with active surveillance. Previously treated more than 1 year ago with radical prostatectomy and undetectable PSA, or definitive radiation therapy and PSA <2 and stable or falling. b) Skin cancers meeting the following criteria: Completely excised carcinoma in situ of any type and basal or squamous cell carcinoma of the skin c.) Other cancers meeting the following criteria: Treated 5 or more years ago with no recurrence since that time
Pre-existing sensory or motor peripheral neuropathy from any cause, grade 1
History of or current progressive multi-focal leukoencephalopathy
Known 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 study drug dose
Receiving or recently treated with any other investigational agent (within 4 weeks of study 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 co-morbidity that in the opinion of the investigator would make administration of ABVD or A2VD hazardous
Infradiaphragmatic disease
Nodular lymphocyte predominant Hodgkin lymphoma
Absence of FDG-avid lymphoma lesions on baseline PET scan
Age 70 years or over, or 17 years and under
Other active cancer (new, relapsed or persistent) within the last 5 years with the exception of: a) Prostate cancer meeting the following criteria: Gleason grade group 1 (Gleason score 6) being managed with active surveillance. Previously treated more than 1 year ago with radical prostatectomy and undetectable PSA, or definitive radiation therapy and PSA <2 and stable or falling. b) Skin cancers meeting the following criteria: Completely excised carcinoma in situ of any type and basal or squamous cell carcinoma of the skin c.) Other cancers meeting the following criteria: Treated 5 or more years ago with no recurrence since that time
Pre-existing sensory or motor peripheral neuropathy from any cause, grade 1
History of or current progressive multi-focal leukoencephalopathy
Known 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 study drug dose
Receiving or recently treated with any other investigational agent (within 4 weeks of study 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 co-morbidity that in the opinion of the investigator would make administration of ABVD or A2VD hazardous
Infradiaphragmatic disease
DESCRIPCIÓN
To assess whether substituting A2VD for ABVD as part of a PET-response adapted design in early stage HL can: improve the Progression Free Survival (PFS)
PALABRAS CLAVE
donor lymphocyte infusion, factor xi, hodgkin, hodgkin lymphoma, leucemia linfocítica crónica (llc / cll), lymphoma
