Fludeoxyglucose F 18 PET Scan-Guided Therapy or Standard Therapy in Treating Patients With Previously Untreated Stage I or Stage II Hodgkin's Lymphoma (H10)

This study has been completed.
Sponsor:
Collaborators:
Lymphoma Study Association
Fondazione Italiana Linfomi ONLUS
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00433433
First received: February 8, 2007
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: ABVD q4 weeks
Drug: BEACOPP escalated q3 weeks
Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)
Procedure: FDG-PET scan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Event-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Long-term toxicity, in terms of secondary malignancies, cardiovascular events, and pulmonary events [ Designated as safety issue: Yes ]

Enrollment: 1952
Study Start Date: October 2006
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Favorable - Standard - any PET outcome
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
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
Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)
Other Name: Involved-Note Radiation Therapy
Procedure: FDG-PET scan
Other Name: F-18 fluorodeoxyglucose positron emission tomography scan
Experimental: Favorable - Experimental - PET negative

ABVDx2 cycles; then FDG-PET evaluation:

PET negative: ABVDx2 without further RT (total of 4 cycles!)

Drug: ABVD q4 weeks
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
Procedure: FDG-PET scan
Other Name: F-18 fluorodeoxyglucose positron emission tomography scan
Experimental: Favorable - Experimental - PET positive

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
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
Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)
Other Name: Involved-Note Radiation Therapy
Procedure: FDG-PET scan
Other Name: F-18 fluorodeoxyglucose positron emission tomography scan
Active Comparator: Unfavorable - Standard - Any PET outcome
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
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
Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)
Other Name: Involved-Note Radiation Therapy
Procedure: FDG-PET scan
Other Name: F-18 fluorodeoxyglucose positron emission tomography scan
Experimental: Unfavorable - Experimental - PET negative

ABVDx2 cycles; then FDG-PET evaluation:

PET negative: ABVDx 4 cycles, without RT (total of 6 cycles)

Drug: ABVD q4 weeks
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
Procedure: FDG-PET scan
Other Name: F-18 fluorodeoxyglucose positron emission tomography scan
Experimental: Unfavorable - Experimental - PET positive

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
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
Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)
Other Name: Involved-Note Radiation Therapy
Procedure: FDG-PET scan
Other Name: F-18 fluorodeoxyglucose positron emission tomography scan

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.

  Eligibility

Ages Eligible for Study:   15 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00433433

Locations
Netherlands
Universitair Medisch Centrum St. Radboud - Nijmegen
Nijmegen, Netherlands, NL-6500 HB
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Lymphoma Study Association
Fondazione Italiana Linfomi ONLUS
Investigators
Principal Investigator: John Raemaekers, MD, PhD EORTC - Universitair Medisch Centrum St. Radboud, Nijmegen, NL
Study Chair: H. Eghbali, MD EORTC - Institut Bergonie, Bordeaux, FR
Principal Investigator: Marc Andre, MD GELA - Centre Hospitalier Notre Dame - Reine Fabiola, Brussels, BE
Study Chair: Oumedaly Reman, MD GELA - CHU de Caen, Caen, FR
Principal Investigator: Massimo Federico, MD GIMEMA- Azienda Ospedaliera - Universitaria di Modena, Modena, IT
Principal Investigator: Ercole Brusamolino, MD GIMEMA - Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, IT
  More Information

Additional Information:
Publications:
André M, Reman O, Fédérico M, et al.: First report on the H10 EORTC/GELA/IIL randomized intergroup trial on early FDG-PET scan guided treatment adaptation versus standard combined modality treatment in patients with supra-diaphragmatic stage I/II Hodgkin's lymphoma, for the Groupe d'Etude Des Lymphomes De l'Adulte (GELA), European Organisation for the Research and Treatment of Cancer (EORTC) Lymphoma Group and the Intergruppo Italiano Linfomi (IIL) . [Abstract] Blood 114 (22): A-97, 2009.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00433433     History of Changes
Other Study ID Numbers: EORTC-20051, EORTC-20051, GELA-H10, IIL-EORTC-20051, EUDRACT-2005-002765-37, EU-20657
Study First Received: February 8, 2007
Last Updated: June 13, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Croatia: Ministry of Health and Social Care
Denmark: Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Switzerland: Swissmedic
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Slovak Republic: State Institute for Drug Control

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
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

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 31, 2014