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

Study Overview
=================
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.

Official Title
-----------------
The H10 EORTC/GELA/IIL Randomized Intergroup Trial on Early FDG-PET Scan Guided Treatment Adaptation Versus Standard Combined Modality Treatment in Patients With Supradiaphragmatic Stage I/II Hodgkin's Lymphoma

Conditions
-----------------
Lymphoma

Intervention / Treatment
-----------------
* Drug: ABVD q4 weeks
* Drug: BEACOPP escalated q3 weeks
* Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)
* Procedure: FDG-PET scan


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: 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 PATIENT CHARACTERISTICS: 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

Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Favorable - Standard - any PET outcome<br>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. | Drug: ABVD q4 weeks<br>* Doxorubicin 25 mg/m2 i.v. day 1 and 15; Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15; Vinblastine 6 mg/m2 i.v. day 1 and 15; Dacarbazine 375 mg/m2 i.v. day 1 and 15<br>Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)<br> <br> * Other names: Involved-Note Radiation Therapy;Procedure: FDG-PET scan<br> <br> * Other names: F-18 fluorodeoxyglucose positron emission tomography scan;|
| Experimental: Favorable - Experimental - PET negative<br>ABVDx2 cycles; then FDG-PET evaluation: PET negative: ABVDx2 without further RT (total of 4 cycles!) | Drug: ABVD q4 weeks<br>* Doxorubicin 25 mg/m2 i.v. day 1 and 15; Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15; Vinblastine 6 mg/m2 i.v. day 1 and 15; Dacarbazine 375 mg/m2 i.v. day 1 and 15<br>Procedure: FDG-PET scan<br> <br> * Other names: F-18 fluorodeoxyglucose positron emission tomography scan;|
| Experimental: Favorable - Experimental - PET positive<br>ABVDx2 cycles; then FDG-PET evaluation: PET positive: presumed poor-risk: switch to escalated BEACOPPx2 + INRT30Gy (+boost 6Gy to residual lesions). | Drug: BEACOPP escalated q3 weeks<br>* Cyclophosphamide 1250 mg/m2 i.v. day 1; Doxorubicin 35 mg/m2 i.v. day 1; Vincristine 1.4 mg/m2 i.v.(max.2mg) day 8; Bleomycin 10 mg/m2 i.v./i.m. day 8; Etoposide 200 mg/m2/ i.v. day 1 to 3; Procarbazine 100 mg/m2 orally day 1 to 7; Prednisone 40 mg/m2 orally day 1 to 14; G-CSF 5 mcg/kg s.c. day 9 to recovery leukocytes>1.0x109/l<br>Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)<br> <br> * Other names: Involved-Note Radiation Therapy;Procedure: FDG-PET scan<br> <br> * Other names: F-18 fluorodeoxyglucose positron emission tomography scan;|
| Active Comparator: Unfavorable - Standard - Any PET outcome<br>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. | Drug: ABVD q4 weeks<br>* Doxorubicin 25 mg/m2 i.v. day 1 and 15; Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15; Vinblastine 6 mg/m2 i.v. day 1 and 15; Dacarbazine 375 mg/m2 i.v. day 1 and 15<br>Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)<br> <br> * Other names: Involved-Note Radiation Therapy;Procedure: FDG-PET scan<br> <br> * Other names: F-18 fluorodeoxyglucose positron emission tomography scan;|
| Experimental: Unfavorable - Experimental - PET negative<br>ABVDx2 cycles; then FDG-PET evaluation: PET negative: ABVDx 4 cycles, without RT (total of 6 cycles) | Drug: ABVD q4 weeks<br>* Doxorubicin 25 mg/m2 i.v. day 1 and 15; Bleomycin 10 mg/m2 i.v./i.m. day 1 and 15; Vinblastine 6 mg/m2 i.v. day 1 and 15; Dacarbazine 375 mg/m2 i.v. day 1 and 15<br>Procedure: FDG-PET scan<br> <br> * Other names: F-18 fluorodeoxyglucose positron emission tomography scan;|
| Experimental: Unfavorable - Experimental - PET positive<br>ABVDx2 cycles; then FDG-PET evaluation: PET positive: presumed poor-risk: switch to escalated BEACOPPx2 + INRT 30Gy (+boost 6Gy to residual lesions). | Drug: BEACOPP escalated q3 weeks<br>* Cyclophosphamide 1250 mg/m2 i.v. day 1; Doxorubicin 35 mg/m2 i.v. day 1; Vincristine 1.4 mg/m2 i.v.(max.2mg) day 8; Bleomycin 10 mg/m2 i.v./i.m. day 8; Etoposide 200 mg/m2/ i.v. day 1 to 3; Procarbazine 100 mg/m2 orally day 1 to 7; Prednisone 40 mg/m2 orally day 1 to 14; G-CSF 5 mcg/kg s.c. day 9 to recovery leukocytes>1.0x109/l<br>Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)<br> <br> * Other names: Involved-Note Radiation Therapy;Procedure: FDG-PET scan<br> <br> * Other names: F-18 fluorodeoxyglucose positron emission tomography scan;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival |  |  | 
| Overall survival |  |  | 
| Long-term toxicity, in terms of secondary malignancies, cardiovascular events, and pulmonary events |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adult mixed cellularity Hodgkin lymphoma, adult nodular sclerosis Hodgkin lymphoma, stage I adult Hodgkin lymphoma, stage II adult Hodgkin lymphoma, adult lymphocyte depletion Hodgkin lymphoma