|Phase III||Supportive care, Treatment||Active||15 to 70||Other||CDR0000531125|
EORTC-20051, GELA-H10, IIL-EORTC-20051, EUDRACT-2005-002765-37, EU-20657, NCT00433433
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Diagnostic procedures, such as fludeoxyglucose F 18 positron emission tomography (FDG-PET scan), may help doctors predict a patient's response to treatment and help plan the best treatment. It is not yet known whether FDG-PET scan-guided therapy is more effective than standard therapy in treating Hodgkin's lymphoma.
PURPOSE: This randomized phase III trial is studying FDG-PET scan-guided therapy to see how well it works compared with standard therapy in treating patients with previously untreated stage I or stage II Hodgkin's lymphoma.
Further Study Information
- Evaluate whether chemotherapy alone is as effective, but less toxic, as combined modality treatment, in terms of progression-free survival (PFS), in patients with favorable or unfavorable supradiaphragmatic stage I or II Hodgkin's lymphoma who are fludeoxglucose F 18 positron emission tomography (FDG-PET) scan negative after two courses of doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD).
- Evaluate whether early change of chemotherapy from ABVD to escalated cyclophosphamide, doxorubicin hydrochloride, vincristine, bleomycin, etoposide, procarbazine hydrochloride, and prednisone (escalated BEACOPP) improves the PFS of patients who are FDG-PET scan positive after two courses of ABVD.
- Confirm that early response by FDG-PET scan is predictive of the outcome of patients randomized to the standard treatment arm.
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to disease prognostic profile (favorable vs unfavorable), participating center, Ann Arbor clinical stage (I vs II), and availability of a baseline fludeoxyglucose F 18 positron emission tomography (FDG-PET) scan (yes vs no). Patients are randomized to 1 of 2 treatment arms.
- Arm I (standard [closed to accrual as of 6/24/2011]): Patients receive ABVD chemotherapy comprising doxorubicin hydrochloride IV, bleomycin IV or intramuscularly (IM), vinblastine IV, and dacarbazine IV on days 1 and 15. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients with favorable prognostic profile receive 3 courses of ABVD. Patients with unfavorable prognostic profile receive 4 courses of ABVD. Patients undergo FDG-PET scan after completion of 2 courses of ABVD. Beginning 3-4 weeks after completion of ABVD, patients undergo involved-node radiotherapy (INRT) 5 days a week for 4-6 weeks.
- Arm II (experimental): Patients receive ABVD as in arm I for 2 courses and then undergo FDG-PET scan. Further treatment is adapted according to FDG-PET scan result.
- FDG-PET negative: Patients with favorable prognostic profile receive 1 additional courses of ABVD. Patients with unfavorable prognostic profile receive 2 additional courses of ABVD. Patients with favorable or unfavorable prognostic profiles randomized on or after August 9th 2010 who are FDG-PET negative after two courses of ABVD will receive standard combined modality treatment consisting of ABVD and INRT as in arm I.
- FDG-PET positive: Patients receive ABVD as in arm I for 2 courses or intensification to escalated BEACOPP chemotherapy comprising cyclophosphamide IV and doxorubicin hydrochloride IV on day 1, vincristine IV and bleomycin IV or IM on day 8, etoposide IV on days 1-3, oral procarbazine hydrochloride on days 1-7, oral prednisone on days 1-14, and filgrastim (G-CSF) subcutaneously beginning on day 9 and continuing until blood count recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks after completion of ABVD or BEACOPP, patients undergo INRT 5 days a week for 4-6 weeks.
After completion of study treatment, patients are followed periodically for at least 10 years.
PROJECTED ACCRUAL: A total of 1,797 patients will be accrued for this study.
- Histologically confirmed Hodgkin's lymphoma
- No nodular lymphocyte-predominant subtype (nodular paragranuloma)
- Supradiaphragmatic Ann Arbor clinical stage I or II disease
- Must meet criteria for 1 of the following prognostic subsets:
- Unfavorable subset, defined as meeting 1 of the following criteria:
- Clinical stage II disease with ≥ 4 nodal areas involved
- Mediastinum and hili are considered as 1 nodal area
- Age ≥ 50 years
- Erythrocyte sedimentation rate (ESR) ≥ 50 mm/hr with no B symptoms
- ESR ≥ 30 mm/hr with B symptoms
- Mediastinum/thoracic (MT) ratio ≥ 0.35
- Favorable subset, defined as meeting all of the following criteria:
- Clinical stage I disease OR stage II disease with ≤ 3 involved areas
- Age < 50 years
- ESR < 50 mm/hr (no B symptoms) OR ESR < 30 mm/hr (B symptoms present)
- MT ratio < 0.35
- Previously untreated disease
- Planning to undergo fludeoxyglucose F 18 positron emission tomography after the first 2 courses of study chemotherapy
- WHO performance status 0-3
- Bilirubin ≤ 2.5 times upper limit of normal (ULN)
- Creatinine ≤ 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No severe cardiac, pulmonary, neurologic, psychiatric, or metabolic disease
- No unstable diabetes mellitus
- No other malignancies within the past 5 years except for basal cell skin cancer or adequately treated carcinoma in situ of the cervix
- No known HIV infection
- No psychological, familial, sociological, or geographical condition that would preclude study compliance
PRIOR CONCURRENT THERAPY:
- Not specified
Trial Lead Organizations/Sponsors
European Organization for Research and Treatment of CancerLymphoma Study Association
Intergruppo Italiano Linfomi
|John Raemaekers||Study Chair|
|Marc Andre||Study Chair|
|Massimo Federico||Study Chair|
|Universitair Medisch Centrum St. Radboud - Nijmegen|
|John Raemaekers, MD, PhD||Ph: 31-24-361-4762|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00433433
Information obtained from ClinicalTrials.gov on November 20, 2012
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