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Combination Chemotherapy With or Without Radiation Therapy in Treating Patients With Hodgkin's Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00005584
First Posted: January 27, 2003
Last Update Posted: July 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Lymphoma Study Association
UNICANCER
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Combining chemotherapy with radiation therapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is most effective in treating Hodgkin's lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of different regimens of combination chemotherapy with or without radiation therapy in treating patients who have Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma Biological: bleomycin sulfate Drug: ABVD regimen Drug: BEACOPP regimen Drug: epirubicin hydrochloride Drug: prednisone Drug: vinblastine sulfate Radiation: radiation therapy Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Prospective Controlled Trial in Clinical Stages I-II Supradiaphragmatic Hodgkin's Disease: Evaluation of Treatment Efficacy, (Long Term) Toxicity and Quality of Life in Two Different Prognostic Subgroups

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Relapse-free rate [ Time Frame: 5 years ]
    with events defined as lack of CR/CRu at the end of treatment or relapse


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Till withdrawal criteria met ]
  • Failure Free Survival [ Time Frame: Till withdrawal criteria met ]
  • Relapse Free Survival [ Time Frame: Till withdrawal criteria met ]

Enrollment: 1649
Study Start Date: October 1998
Primary Completion Date: May 2004 (Final data collection date for primary outcome measure)
  Hide Detailed Description

Detailed Description:

OBJECTIVES:

  • Compare the late toxicity of 6 courses of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by involved-field radiotherapy (IF-RT) (36 Gy) vs IF-RT (20 Gy), vs no IF-RT (closed to accrual as of 6/2002) in patients with supradiaphragmatic Hodgkin's lymphoma, favorable prognosis, and complete remission (CR) or CR unconfirmed after completion of chemotherapy. (Favorable prognosis group [group 1] closed to accrual as of 4/28/04.)
  • Compare 6 courses of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) vs 4 courses of ABVD vs 4 courses of cyclophosphamide, doxorubicin, vincristine, bleomycin, etoposide, procarbazine, and prednisone (BEACOPP) followed by IF-RT, with respect to overall survival and late treatment-related toxicity, in patients with supradiaphragmatic Hodgkin's lymphoma and unfavorable prognosis. (Unfavorable prognosis group [group 2] closed to accrual as of 9/2002.) (Favorable prognosis group [group 1] closed to accrual as of 4/28/04.)
  • Maintain the failure-free survival and relapse-free survival rates that were reached in the previous EORTC studies (H5 to H8), with a reduction in acute and delayed side effects of the treatment, in particular that of severe late radiotherapy and chemotherapy-related toxicity.
  • Compare the quality of life, overall survival, treatment quality control, and duration of treatment in patients with favorable (closed to accrual as of 4/28/04) or unfavorable (closed to accrual as of 9/2002) prognoses treated with these regimens.
  • Determine the efficacy of conservative therapy comprised of observation until disease progression (DP) and administration of IF-RT at the time of DP in patients with lymphocyte-predominant Hodgkin's lymphoma, nodular subtype (nodular paragranuloma).

OUTLINE: This is a randomized, multicenter study.

Patients with classical Hodgkin's lymphoma are assigned to 1 of 2 randomized groups. (Group 2 [unfavorable prognosis] closed to accrual as of 9/2002.) (Group 1 [favorable prognosis] closed to accrual as of 4/28/04.) Patients with lymphocyte-predominant Hodgkin's lymphoma are assigned to the nonrandomized group.

Randomized groups

  • Patients are stratified by prognosis (favorable vs unfavorable). Patients are assigned to 1 of 2 treatment groups based on prognosis. (Group 2 [unfavorable prognosis] closed to accrual as of 9/2002.) (Group 1 [favorable prognosis] closed to accrual as of 4/28/04.)

    • Group 1 (favorable prognosis) (closed to accrual as of 4/28/04): Patients receive epirubicin IV over 5 minutes, bleomycin intramuscularly (IM) (or IV if necessary), and vinblastine IV on day 1 and oral prednisone on days 1-5. Treatment repeats every 3 weeks for 6 courses. Patients are then assigned to 1 of 3 involved-field radiotherapy (IF-RT) groups based on response to chemotherapy:

      • Group A (complete remission (CR) or CR unconfirmed [CRu]) Patients are randomized to 1 of 3 radiotherapy arms. (Arm III closed to accrual as of 6/2002.)

        • Arm I (36 Gy): Patients undergo IF-RT 5 days a week for 3.5 weeks.
        • Arm II (20 Gy): Patients undergo IF-RT 5 days a week for 2 weeks.
        • Arm III (closed to accrual as of 6/2002): Patients undergo no IF-RT.
      • Group B (partial remission [PR]): Patients undergo IF-RT 5 days a week for 3.5 weeks and boost radiotherapy.
      • Group C (stable disease or disease progression [DP]): Patients receive no IF-RT and are taken off study.
    • Group 2 (unfavorable prognosis) (closed to accrual as of 9/2002): Patients are randomized to 1 of 3 treatment arms.

      • Arm I: Patients receive doxorubicin IV over 5 minutes, bleomycin IM (or IV if necessary), vinblastine IV, and dacarbazine IV over 5-10 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses.
      • Arm II: Patients receive chemotherapy as in arm I. Treatment repeats every 4 weeks for 4 courses.
      • Arm III: Patients receive cyclophosphamide IV and doxorubicin IV over 5 minutes on day 1, vincristine IV and bleomycin IM (or IV if necessary) on day 8, etoposide IV over a minimum of 30 minutes on days 1-3, oral procarbazine on days 1-7, and oral prednisone on days 1-14. Treatment repeats every 3 weeks for 4 courses.

Patients on all arms who achieve CR or CRu undergo IF-RT 5 days a week for 3 weeks. Patients who achieve PR undergo IF-RT 5 days a week for 3.5 weeks and boost radiotherapy.

  • Groups 1 and 2 (group 2 closed to accrual as of 9/2002) (group 1 closed to accrual as of 4/28/04): IF-RT begins within 3-4 weeks after completion of the last course of chemotherapy.

Nonrandomized group

  • Patients with completely resected stage I disease undergo observation until DP and undergo IF-RT after documentation of DP. Patients with stage II or incompletely resected stage I disease undergo IF-RT immediately.

Quality of life is assessed before starting study therapy, immediately after completion of study, and then annually for 10 years.

Patients are followed at 2, 4, 6, 9, and 12 months; every 4 months for 1 year; every 6 months for 3 years; and then annually thereafter.

PROJECTED ACCRUAL: A total of 903 patients (group 1) will be accrued for this study within 7.7 years. A total of 723 patients (group 2) will be accrued for this study within 3.8 years. (Group 2 [unfavorable prognosis] closed to accrual as of 9/2002.) (Group 1 [favorable prognosis] closed to accrual as of 4/28/04.)

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   15 Years to 70 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Randomized groups: Histologically proven previously untreated stage I or II supradiaphragmatic Hodgkin's lymphoma

    • No prior staging laparotomy
    • Favorable (closed to accrual as of 4/28/04) or unfavorable (closed to accrual as of 9/2002) prognosis
  • Nonrandomized group: Histologically proven lymphocyte-predominant Hodgkin's lymphoma, nodular subtype (nodular paragranuloma)

    • Stage I with complete or incomplete resection OR
    • Stage II

PATIENT CHARACTERISTICS:

Age:

  • 15 to 70

Performance status:

  • WHO 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Not specified

Renal:

  • Not specified

Cardiovascular:

  • No severe cardiac disease that would interfere with normal life expectancy or study treatment

Pulmonary:

  • No severe pulmonary disease that would interfere with normal life expectancy or study treatment

Other:

  • No other prior or concurrent malignancy except basal cell skin cancer or carcinoma in situ of the cervix
  • No severe neurologic or metabolic disease that would interfere with normal life expectancy or study treatment
  • No psychologic, familial, socioeconomic, or geographic circumstances that would preclude proper staging or compliance
  • HIV negative
  • Not pregnant
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior biologic therapy for this malignancy

Chemotherapy

  • No prior chemotherapy for this malignancy

Endocrine therapy

  • No prior endocrine therapy for this malignancy

Radiotherapy

  • No prior radiotherapy for this malignancy

Surgery

  • No prior surgery for this malignancy
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00005584


  Show 121 Study Locations
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Lymphoma Study Association
UNICANCER
Investigators
Study Chair: Jose Thomas, MD University Hospital, Gasthuisberg
Study Chair: H. Eghbali, MD Institut Bergonié
Study Chair: E.M. Noordijk, MD Leiden University Medical Center
Study Chair: Christophe Ferme Centre Medical de Bligny
Study Chair: Christian Gisselbrecht, MD Hopital Saint-Louis
Study Chair: Thierry O. Philip, MD Centre Leon Berard
  More Information

Publications:
Eghbali H, Brice P, Creemers GY, et al.: Comparison of three radiation dose levels after EBVP regimen in favorable supradiaphragmatic clinical stages (CS) I-II Hodgkin's lymphoma (HL): preliminary results of the EORTC-GELA H9-F trial. [Abstract] Blood 106 (11): A-814, 2005.
Ferme C, Diviné M, Vranovsky A, et al.: Four ABVD and involved-field radiotherapy in unfavorable supradiaphragmatic clinical stages (CS) I-II Hodgkin's lymphoma (HL): preliminary results of the EORTC-GELA H9-U trial. [Abstract] Blood 106 (11): A-813, 2005.
Girinsky T, Gargi T, Carrie C, et al.: Quality assurance program in the EORTC-GELA H9 randomized study results on 282 patients. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A77, S47, 2005.
Noordijk EM, Thomas J, Fermé C, et al.: First results of the EORTC-GELA H9 randomized trials: the H9-F trial (comparing 3 radiation dose levels) and H9-U trial (comparing 3 chemotherapy schemes) in patients with favorable or unfavorable early stage Hodgkin's lymphoma (HL) . [Abstract] J Clin Oncol 23 (Suppl 16): A-6505, 561s, 2005.
Thomas J, Ferme C, Noordijk EM, et al.: Six cycles of EBVP followed by 36 Gy involved-field irradiation vs. no irradiation in favourable supradiaphragmatic clinical stages I-II Hodgkin's lymphoma: the EORTC-GELA strategy in 771 patients (H9-F trial-20982). [Abstract] Eur J Haematol 75 (Suppl 65): A-E11a, 40, 2004.
Thomas J, Ferme C, Noordijk EM, et al.: Six cycles of ABVD + IF-RT vs. four cycles of ABVD + IF-RT vs. four cycles of BEACOPP + IF-RT in unfavourable supradiaphragmatic clinical stages I-II Hodgkin's lymphoma: the EORTC-GELA H9-U randomized clinical trial (20982) in 808 patients. [Abstract] Eur J Haematol 73 (Supp 65): A-E12, 40, 2004.

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00005584     History of Changes
Other Study ID Numbers: EORTC-20982
FRE-FNCLCC-98014 ( Other Identifier: FRE-FNCLCC )
GELA-H9 ( Other Identifier: GELA )
First Submitted: May 2, 2000
First Posted: January 27, 2003
Last Update Posted: July 27, 2017
Last Verified: July 2017

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma
adult lymphocyte predominant Hodgkin lymphoma

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Prednisone
Epirubicin
Bleomycin
Vinblastine
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators