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

NCT ID: NCT00433433

Last Updated: 2021-02-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

1952 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-10-31

Brief Summary

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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

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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.

Conditions

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Lymphoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

ABVD q4 weeks

Intervention Type DRUG

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

IN-RT 30 Gy (+ boost 6 Gy residual)

Intervention Type RADIATION

FDG-PET scan

Intervention Type PROCEDURE

Favorable - Experimental - PET negative

ABVDx2 cycles; then FDG-PET evaluation:

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

Group Type EXPERIMENTAL

ABVD q4 weeks

Intervention Type DRUG

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

FDG-PET scan

Intervention Type PROCEDURE

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).

Group Type EXPERIMENTAL

BEACOPP escalated q3 weeks

Intervention Type DRUG

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

IN-RT 30 Gy (+ boost 6 Gy residual)

Intervention Type RADIATION

FDG-PET scan

Intervention Type PROCEDURE

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.

Group Type ACTIVE_COMPARATOR

ABVD q4 weeks

Intervention Type DRUG

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

IN-RT 30 Gy (+ boost 6 Gy residual)

Intervention Type RADIATION

FDG-PET scan

Intervention Type PROCEDURE

Unfavorable - Experimental - PET negative

ABVDx2 cycles; then FDG-PET evaluation:

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

Group Type EXPERIMENTAL

ABVD q4 weeks

Intervention Type DRUG

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

FDG-PET scan

Intervention Type PROCEDURE

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).

Group Type EXPERIMENTAL

BEACOPP escalated q3 weeks

Intervention Type DRUG

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

IN-RT 30 Gy (+ boost 6 Gy residual)

Intervention Type RADIATION

FDG-PET scan

Intervention Type PROCEDURE

Interventions

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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

Intervention Type 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

Intervention Type DRUG

IN-RT 30 Gy (+ boost 6 Gy residual)

Intervention Type RADIATION

FDG-PET scan

Intervention Type PROCEDURE

Other Intervention Names

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Involved-Note Radiation Therapy F-18 fluorodeoxyglucose positron emission tomography scan

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

15 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lymphoma Study Association

OTHER

Sponsor Role collaborator

Fondazione Italiana Linfomi - ETS

OTHER

Sponsor Role collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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John Raemaekers, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

EORTC - Universitair Medisch Centrum St. Radboud, Nijmegen, NL

H. Eghbali, MD

Role: STUDY_CHAIR

EORTC - Institut Bergonie, Bordeaux, FR

Marc Andre, MD

Role: PRINCIPAL_INVESTIGATOR

GELA - Centre Hospitalier Notre Dame - Reine Fabiola, Brussels, BE

Oumedaly Reman, MD

Role: STUDY_CHAIR

GELA - CHU de Caen, Caen, FR

Massimo Federico, MD

Role: PRINCIPAL_INVESTIGATOR

GIMEMA- Azienda Ospedaliera - Universitaria di Modena, Modena, IT

Ercole Brusamolino, MD

Role: PRINCIPAL_INVESTIGATOR

GIMEMA - Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, IT

Locations

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Universitair Medisch Centrum St. Radboud - Nijmegen

Nijmegen, , Netherlands

Site Status

Countries

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Netherlands

References

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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.

Reference Type RESULT

Kreuzberger N, Goldkuhle M, von Tresckow B, Kobe C, Sickinger MT, Monsef I, Skoetz N. Positron emission tomography-adapted therapy for first-line treatment in adults with Hodgkin lymphoma. Cochrane Database Syst Rev. 2025 Mar 26;3(3):CD010533. doi: 10.1002/14651858.CD010533.pub3.

Reference Type DERIVED
PMID: 40135712 (View on PubMed)

Phillips EH, Counsell N, Illidge T, Andre M, Aurer I, Fiaccadori V, Fortpied C, Neven A, Federico M, Barrington SF, Raemaekers J, Radford J. Maximum tumor diameter is associated with relapse risk in limited-stage Hodgkin lymphoma: an international study. Blood Adv. 2025 May 13;9(9):2266-2274. doi: 10.1182/bloodadvances.2024015140.

Reference Type DERIVED
PMID: 39774828 (View on PubMed)

Fiaccadori V, Neven A, Fortpied C, Aurer I, Andre M, Federico M, Counsell N, Phillips EH, Clifton-Hadley L, Barrington SF, Illidge T, Radford J, Raemaekers JMM. Relapse patterns in early-PET negative, limited-stage Hodgkin lymphoma (HL) after ABVD with or without radiotherapy-a joint analysis of EORTC/LYSA/FIL H10 and NCRI RAPID trials. Br J Haematol. 2023 Mar;200(6):731-739. doi: 10.1111/bjh.18594. Epub 2022 Dec 21.

Reference Type DERIVED
PMID: 36541117 (View on PubMed)

Cottereau AS, Versari A, Loft A, Casasnovas O, Bellei M, Ricci R, Bardet S, Castagnoli A, Brice P, Raemaekers J, Deau B, Fortpied C, Raveloarivahy T, Van Zele E, Chartier L, Vander Borght T, Federico M, Hutchings M, Ricardi U, Andre M, Meignan M. Prognostic value of baseline metabolic tumor volume in early-stage Hodgkin lymphoma in the standard arm of the H10 trial. Blood. 2018 Mar 29;131(13):1456-1463. doi: 10.1182/blood-2017-07-795476. Epub 2018 Feb 1.

Reference Type DERIVED
PMID: 29437590 (View on PubMed)

Raemaekers JM, Andre MP, Federico M, Girinsky T, Oumedaly R, Brusamolino E, Brice P, Ferme C, van der Maazen R, Gotti M, Bouabdallah R, Sebban CJ, Lievens Y, Re A, Stamatoullas A, Morschhauser F, Lugtenburg PJ, Abruzzese E, Olivier P, Casasnovas RO, van Imhoff G, Raveloarivahy T, Bellei M, van der Borght T, Bardet S, Versari A, Hutchings M, Meignan M, Fortpied C. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014 Apr 20;32(12):1188-94. doi: 10.1200/JCO.2013.51.9298. Epub 2014 Mar 17.

Reference Type DERIVED
PMID: 24637998 (View on PubMed)

Other Identifiers

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EORTC-20051

Identifier Type: -

Identifier Source: secondary_id

GELA-H10

Identifier Type: -

Identifier Source: secondary_id

IIL-EORTC-20051

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2005-002765-37

Identifier Type: -

Identifier Source: secondary_id

EU-20657

Identifier Type: -

Identifier Source: secondary_id

EORTC-20051

Identifier Type: -

Identifier Source: org_study_id

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