CRUK‐07/146.

Trial name or title	A randomised phase III trial to assess response‐adapted therapy using FDG‐PET imaging in individuals with newly diagnosed, advanced HL
Methods	Study design Participants undergo FDG‐PET/CT imaging at baseline, then receive ABVD chemotherapy, and between days 22 and 25 of course 2, they undergo a second FDG‐PET/CT scan to assess response. Subsequent therapy is based on FDG‐PET/CT scan results PET2 (after 2 cycles)‐negative Arm I (ABVD chemotherapy): participants receive ABVD chemotherapy comprising doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity Arm II (AVD chemotherapy): participants receive AVD chemotherapy comprising doxorubicin hydrochloride IV, vinblastine IV and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity PET2‐positive BEACOPP‐14 chemotherapy BEACOPPesc chemotherapy After completion of BEACOPP chemotherapy, participants undergo a third FDG‐PET/CT scan to assess response PET3 (after 3 cycles)‐negative 2 x BEACOPP‐14 or 1 x BEACOPPesc PET3‐positive Radiotherapy to sites of FDG uptake or salvage chemotherapy After completion of study therapy, participants are followed every 3 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter
Participants	Age Minimum: 18 years Maximum: not available Gender Both Eligibility DISEASE CHARACTERISTICS Histologically confirmed classic HL meeting the following criteria. Current WHO classification criteria (i.e. nodular sclerosis, mixed cellularity, lymphocyte rich and lymphocyte‐depleted) Clinical stage IIB, III or IV disease OR clinical stage IIA disease with adverse features, including any of the following Bulk mediastinal disease, defined as maximal transverse diameter of mass > 0.33 of the internal thoracic diameter at D5/6 interspace on routine chest X‐ray Disease outside the mediastinum and lymph node or lymph node mass > 10 cm in diameter More than two sites of disease Other poor‐risk features that require treatment with full course combination chemotherapy Newly diagnosed disease No CNS or meningeal involvement by lymphoma Participant characteristics ECOG performance status 0‐3 (Oken 1982) Life expectancy > 3 months ANC > 1500/mm3 (unless there is bone marrow infiltration by lymphoma) Platelet count > 100,000/mm3 (unless there is bone marrow infiltration by lymphoma) Creatinine < 150% of upper limit of normal (ULN) Bilirubin < 2.0 times ULN (unless attributed to lymphoma) Transaminases < 2.5 times ULN (unless attributed to lymphoma) LVEF ≥ 50% (in participants with a significant history of ischaemic heart disease or hypertension) Diffusion capacity within 25% of normal predicted value by lung function testing Not pregnant or nursing Negative pregnancy test Fertile participants must use effective contraception Amenable to the administration of a full course of chemotherapy, according to the investigator Must have access to PET/CT scanning No poorly controlled diabetes mellitus No cardiac contraindication to doxorubicin hydrochloride, including abnormal contractility by ECHO or MUGA (Multigated acquisition scan) No neurological contraindication to chemotherapy (e.g. pre‐existing neuropathy) No other concurrent uncontrolled medical condition No other active malignant disease within the past 10 years, except fully excised basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the uterine cervix No known positivity for HIV, hepatitis B surface antigen or hepatitis C Routine testing, in the absence of risk factors, is not required No medical or psychiatric condition that compromises the participant's ability to give informed consent Country England, United Kingdom
Interventions	No prior chemotherapy, radiotherapy or other investigational drug for HL Chemotherapy ABVD Doxorubicin hydrochloride IV, bleomycin IV, vinblastine IV and dacarbazine IV on days 1 and 15 Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity BEACOPP‐14 Doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1‐3; oral procarbazine hydrochloride and oral prednisolone on days 1‐7; and bleomycin IV and vincristine IV on day 8 Filgrastim (G‐CSF) SC on days 8‐13 OR pegfilgrastim SC once on day 8 Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity BEACOPPesc Doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; etoposide IV on days 1‐3; oral procarbazine hydrochloride on days 1‐7; oral prednisolone on days 1‐14; and bleomycin IV and vincristine IV on day 8 G‐CSF SC beginning on day 8 and continuing until blood counts recover OR pegfilgrastim SC once on day 8 Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity FDG‐PET scan
Outcomes	3‐year progression‐free survival Overall survival Acute and chronic toxicity as assessed by NCI CTCAE v3.0
Starting date	August 2008
Contact information	Peter Johnson, MD Tel: 44‐2380‐796‐186 johnsonp@soton.ac.uk Southampton General Hospital Southampton England SO16 6YD
Notes	Estimated enrolment: 1200 Estimated completion date: September 2012 Study status according to ClinicalTrials.gov: recruitment status currently unknown