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)

February 2, 2021 updated by: European Organisation for Research and Treatment of Cancer - EORTC

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1952

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Nijmegen, Netherlands, NL-6500 HB
        • Universitair Medisch Centrum St. Radboud - Nijmegen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

15 years to 70 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Procedure: FDG-PET scan
Other Names:
  • F-18 fluorodeoxyglucose positron emission tomography scan
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 Names:
  • Involved-Note Radiation Therapy
Experimental: Favorable - Experimental - PET negative

ABVDx2 cycles; then FDG-PET evaluation:

PET negative: ABVDx2 without further RT (total of 4 cycles!)
Procedure: FDG-PET scan
Other Names:
  • F-18 fluorodeoxyglucose positron emission tomography scan
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
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).
Procedure: FDG-PET scan
Other Names:
  • F-18 fluorodeoxyglucose positron emission tomography scan
Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)
Other Names:
  • Involved-Note Radiation Therapy
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
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.
Procedure: FDG-PET scan
Other Names:
  • F-18 fluorodeoxyglucose positron emission tomography scan
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 Names:
  • Involved-Note Radiation Therapy
Experimental: Unfavorable - Experimental - PET negative

ABVDx2 cycles; then FDG-PET evaluation:

PET negative: ABVDx 4 cycles, without RT (total of 6 cycles)
Procedure: FDG-PET scan
Other Names:
  • F-18 fluorodeoxyglucose positron emission tomography scan
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
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).
Procedure: FDG-PET scan
Other Names:
  • F-18 fluorodeoxyglucose positron emission tomography scan
Radiation: IN-RT 30 Gy (+ boost 6 Gy residual)
Other Names:
  • Involved-Note Radiation Therapy
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Progression-free survival

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Collaborators

Fondazione Italiana Linfomi ONLUS
Lymphoma Study Association

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2006

Primary Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

February 8, 2007

First Submitted That Met QC Criteria

February 8, 2007

First Posted (Estimate)

February 12, 2007

Study Record Updates

Last Update Posted (Actual)

February 3, 2021

Last Update Submitted That Met QC Criteria

February 2, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-20051
  • GELA-H10
  • IIL-EORTC-20051
  • EUDRACT-2005-002765-37
  • EU-20657

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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