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Fludeoxyglucose F 18 PET Scan-Guided Therapy or Standard Therapy in Treating Patients With Previously Untreated Stage I or Stage II Hodgkin's Lymphoma

Phase 3
Conditions
Lymphoma
Interventions
Drug: ABVD q4 weeks
Drug: BEACOPP escalated q3 weeks
Procedure: FDG-PET scan
Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)
Registration Number
NCT00433433
Lead Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
Brief Summary

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.

Detailed Description

OBJECTIVES:

Primary

* 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).

Secondary

* 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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
1952
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Favorable - Experimental - PET negativeABVD q4 weeksABVDx2 cycles; then FDG-PET evaluation: PET negative: ABVDx2 without further RT (total of 4 cycles!)
Favorable - Experimental - PET negativeFDG-PET scanABVDx2 cycles; then FDG-PET evaluation: PET negative: ABVDx2 without further RT (total of 4 cycles!)
Favorable - Standard - any PET outcomeABVD q4 weeksABVDx3 cycles + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions); FDG-PET after two cycles of ABVD for comparison with the experimental arm will be performed but no treatment adaptation will take place.
Favorable - Standard - any PET outcomeIN-RT 30 Gy (+ boost 6 Gy residual)ABVDx3 cycles + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions); FDG-PET after two cycles of ABVD for comparison with the experimental arm will be performed but no treatment adaptation will take place.
Favorable - Standard - any PET outcomeFDG-PET scanABVDx3 cycles + Involved node RT (IN-RT) 30 Gy (+boost of 6Gy to residual lesions); FDG-PET after two cycles of ABVD for comparison with the experimental arm will be performed but no treatment adaptation will take place.
Favorable - Experimental - PET positiveIN-RT 30 Gy (+ boost 6 Gy residual)ABVDx2 cycles; then FDG-PET evaluation: PET positive: presumed poor-risk: switch to escalated BEACOPPx2 + INRT30Gy (+boost 6Gy to residual lesions).
Favorable - Experimental - PET positiveBEACOPP escalated q3 weeksABVDx2 cycles; then FDG-PET evaluation: PET positive: presumed poor-risk: switch to escalated BEACOPPx2 + INRT30Gy (+boost 6Gy to residual lesions).
Favorable - Experimental - PET positiveFDG-PET scanABVDx2 cycles; then FDG-PET evaluation: PET positive: presumed poor-risk: switch to escalated BEACOPPx2 + INRT30Gy (+boost 6Gy to residual lesions).
Unfavorable - Standard - Any PET outcomeABVD q4 weeksABVDx4 cycles + IN-RT 30Gy (+boost 6Gy to residual lesions). FDG-PET after two cycles of ABVD for comparison with the experimental arm will be performed but no treatment adaptation will take place.
Unfavorable - Standard - Any PET outcomeIN-RT 30 Gy (+ boost 6 Gy residual)ABVDx4 cycles + IN-RT 30Gy (+boost 6Gy to residual lesions). FDG-PET after two cycles of ABVD for comparison with the experimental arm will be performed but no treatment adaptation will take place.
Unfavorable - Standard - Any PET outcomeFDG-PET scanABVDx4 cycles + IN-RT 30Gy (+boost 6Gy to residual lesions). FDG-PET after two cycles of ABVD for comparison with the experimental arm will be performed but no treatment adaptation will take place.
Unfavorable - Experimental - PET negativeABVD q4 weeksABVDx2 cycles; then FDG-PET evaluation: PET negative: ABVDx 4 cycles, without RT (total of 6 cycles)
Unfavorable - Experimental - PET negativeFDG-PET scanABVDx2 cycles; then FDG-PET evaluation: PET negative: ABVDx 4 cycles, without RT (total of 6 cycles)
Unfavorable - Experimental - PET positiveBEACOPP escalated q3 weeksABVDx2 cycles; then FDG-PET evaluation: PET positive: presumed poor-risk: switch to escalated BEACOPPx2 + INRT 30Gy (+boost 6Gy to residual lesions).
Unfavorable - Experimental - PET positiveIN-RT 30 Gy (+ boost 6 Gy residual)ABVDx2 cycles; then FDG-PET evaluation: PET positive: presumed poor-risk: switch to escalated BEACOPPx2 + INRT 30Gy (+boost 6Gy to residual lesions).
Unfavorable - Experimental - PET positiveFDG-PET scanABVDx2 cycles; then FDG-PET evaluation: PET positive: presumed poor-risk: switch to escalated BEACOPPx2 + INRT 30Gy (+boost 6Gy to residual lesions).
Primary Outcome Measures
NameTimeMethod
Progression-free survival
Secondary Outcome Measures
NameTimeMethod
Event-free survival
Overall survival
Long-term toxicity, in terms of secondary malignancies, cardiovascular events, and pulmonary events

Trial Locations

Locations (1)

Universitair Medisch Centrum St. Radboud - Nijmegen

🇳🇱

Nijmegen, Netherlands

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