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NCT00003389 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2023-06-29

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 more than one drug 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: This randomized phase III trial is studying two different combination chemotherapy regimens and comparing how well they work, with or without radiation therapy, in treating patients with Hodgkin's lymphoma.

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Failure-free Survival at 5 Years

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outcome · POSTED

5-year Overall Survival

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outcome · POSTED

Incidence of Second Cancers

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion criteria: * Histologically proven previously untreated classical Hodgkin's lymphoma * The following stages are eligible: * Locally extensive: Stage I-IIA/B with massive mediastinal adenopathy * Advanced: Stage III or IV * Measurable or evaluable disease * Age of 16 and over * ECOG Performance status 0-2 * Disease-free of prior invasive malignancies for \>5 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix * White blood cell (WBC) at least 4,000/mm³, (unless documented bone marrow involvement) * Platelet count at least 100,000/mm³ (unless documented bone marrow involvement) * Bilirubin no greater than 5.0 mg/dL * Creatinine no greater than 2.0 mg/dL * Ejection fraction determination recommended if over age 50 and/or have a history of cardiac disease * Fertile patients must use effective contraception * Prior corticosteroids allowed * Prior surgery allowed Exclusion criteria: * Pregnant or nursing * Prior radiotherapy * Prior chemotherapy * Human immunodeficiency virus (HIV) positive
healthy Volunteers
false
minimum Age
16 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
  3. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Arm A (ABVD): Patients receive doxorubicin (25 mg/m²), bleomycin (10 u/m²), vinblastine (6 mg/m²), and dacarbazine (375 mg/m²) intravenously (IV) on days 1 and 15. Courses repeat every 28 days. Patients are restaged after 4 courses. Patients who are in complete remission receive 2 additional courses. Patients with a partial response or less are evaluated after 6 courses, and if there is an ongoing response, patients may receive 2 additional courses for a total of 8. If no ongoing response is observed, patients are removed from the study. All patients with massive mediastinal disease, regardless of stage, receive radiotherapy 2-3 weeks after completion of chemotherapy.
    intervention Names
    1. Drug: Doxorubicin
    2. Drug: Bleomycin
    3. Drug: Vinblastine
    4. Drug: Dacarbazine
    5. Radiation: Radiotherapy
    label
    Arm A (ABVD)
    type
    EXPERIMENTAL
  2. description
    Arm B (Stanford V): Patients receive Stanford V chemotherapy comprising doxorubicin (25 mg/m²) and vinblastine (6 mg/m²) IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; vincristine (1.4 mg/m²) and bleomycin (5 u/m²) IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; mechlorethamine (6 mg/m²) IV on day 1 of weeks 1, 5, and 9 (if mechlorethamine is unavailable, may substitute with cyclophosphamide \[375 mg/m²\] IV); etoposide (60 mg/m²) IV on days 1 and 2 of weeks 3, 7, and 11; and oral prednisone (40 mg/m²) every other day of weeks 1-9 followed by a taper. All patients with bulky disease receive radiotherapy 2-3 weeks after completion of chemotherapy.
    intervention Names
    1. Drug: Doxorubicin
    2. Drug: Bleomycin
    3. Drug: Vinblastine
    4. Drug: Vincristine
    5. Drug: Mechlorethamine
    6. Drug: Etoposide
    7. Drug: Prednisone
    8. Drug: Cyclophosphamide
    9. Radiation: Radiotherapy
    label
    Arm B (Stanford V)
    type
    ACTIVE_COMPARATOR
interventions
  1. arm Group Labels
    1. Arm A (ABVD)
    2. Arm B (Stanford V)
    description
    given IV
    name
    Doxorubicin
    other Names
    1. Adriamycin
    2. Rubex
    3. Adriamycin RDF
    4. Adriamycin PFS
    5. hydroxydaunorubicin
    6. hydroxydaunomycin
    7. ADR
    type
    DRUG
  2. arm Group Labels
    1. Arm A (ABVD)
    2. Arm B (Stanford V)
    description
    given IV
    name
    Bleomycin
    other Names
    1. Blenoxane
    2. BLM
    3. Bleo
    type
    DRUG
  3. arm Group Labels
    1. Arm A (ABVD)
    2. Arm B (Stanford V)
    description
    given IV
    name
    Vinblastine
    other Names
    1. Velban
    2. vinblastine sulfate
    3. vincaleukoblastine
    4. VLB
    5. Velsar
    6. Alkaban AQ
    type
    DRUG
  4. arm Group Labels
    1. Arm A (ABVD)
    description
    given IV
    name
    Dacarbazine
    other Names
    1. DTIC
    2. DTIC-Dome
    3. DIC
    4. imidazole carboxamide
    5. dimethyl triazeno imidazole carboxamide
    type
    DRUG
  5. arm Group Labels
    1. Arm B (Stanford V)
    description
    given IV
    name
    Vincristine
    other Names
    1. Oncovin
    2. Vincasar PFS
    3. vincristine sulfate
    4. VCR
    5. leurocristine
    6. LCR
    type
    DRUG
  6. arm Group Labels
    1. Arm B (Stanford V)
    description
    given IV
    name
    Mechlorethamine
    other Names
    1. Mustargen
    2. nitrogen mustard
    type
    DRUG
  7. arm Group Labels
    1. Arm B (Stanford V)
    description
    given IV
    name
    Etoposide
    other Names
    1. VP-16
    2. VePesid
    3. VP-16-213
    4. EPEG
    5. epipodophyllotoxin
    type
    DRUG
  8. arm Group Labels
    1. Arm B (Stanford V)
    description
    taken orally
    name
    Prednisone
    other Names
    1. Deltasone
    2. Orasone
    3. Medicorten
    4. Panasol-S
    5. Liquid-Pred
    type
    DRUG
  9. arm Group Labels
    1. Arm B (Stanford V)
    description
    given IV
    name
    Cyclophosphamide
    other Names
    1. Cytoxan
    2. Neosar
    3. CTX
    4. CPM
    type
    DRUG
  10. arm Group Labels
    1. Arm A (ABVD)
    2. Arm B (Stanford V)
    name
    Radiotherapy
    type
    RADIATION
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
854
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    Failure-free survival is defined as the time from randomization to the earlier of progression/relapse or death. The 5-year failure-free survival is the probability a patient is failure-free and survives 5 years. Progression is defined as an increase in size of 25% of the sum of the products of the pretreatment measurements or appearance of new lesions. Significant enlargement of the liver or spleen is evidence of progression. A significant increase in size is defined as \> 2.0 cm in distance between costal margin and the inferior margin of either organ. Relapse is defined as the re-appearance of any clinical evidence of Hodgkin's disease in a patient who has had a complete response. Relapse for partial responders is defined as progressive disease relative to disease status during the partial remission.
    measure
    Failure-free Survival at 5 Years
    time Frame
    Assessed every 2 months if patient is < 1 year from study entry, every 3 months for the second year, every 4 months for the third year, every 6 months for years 4 and 5
secondary Outcomes
  1. description
    Overall survival is defined as the time from randomization to death or last known alive. The 5-year survival rate is the probability a patient survives 5 years.
    measure
    5-year Overall Survival
    time Frame
    Assessed every 2 months if patient is < 1 year from study entry, every 3 months for the second year, every 4 months for the third year, every 6 months for years 4 and 5, and yearly for 5 years
  2. description
    Number of patients who developed second primary cancers
    measure
    Incidence of Second Cancers
    time Frame
    Assessed every 2 months if patient is < 1 year from study entry, every 3 months for the second year, every 4 months for the third year, every 6 months for years 4 and 5, and yearly for 5 years
Full study description
brief Summary
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 more than one drug 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: This randomized phase III trial is studying two different combination chemotherapy regimens and comparing how well they work, with or without radiation therapy, in treating patients with Hodgkin's lymphoma.
detailed Description
OBJECTIVES: * Compare the failure-free survival of patients with locally extensive or advanced Hodgkin's lymphoma treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) vs doxorubicin, vinblastine, vincristine, bleomycin, mechlorethamine, etoposide, and prednisone (Stanford V) with or without radiotherapy. * Compare the overall survival and freedom from progression in these patients at 5 and 10 years after treatment with these regimens. * Compare pulmonary function, incidence of second cancers, reproductive function, and deaths from causes other than Hodgkin's lymphoma in patients treated with these regimens. OUTLINE: This is a randomized study. Patients are stratified according to number of adverse risk factors (0-2 vs 3-7), disease characteristics (locally extensive vs advanced) and time of entry (before addendum 6 vs. after addendum 6). Patients are randomized to 1 of 2 treatment arms. * Arm A (ABVD): Patients receive doxorubicin (25 mg/m²), bleomycin (10 u/m²), vinblastine (6 mg/m²), and dacarbazine (375 mg/m²) IV on days 1 and 15. Courses repeat every 28 days. Patients are restaged after 4 courses. Patients who are in complete remission receive 2 additional courses. Patients with a partial response or less are evaluated after 6 courses, and if there is an ongoing response, patients may receive 2 additional courses for a total of 8. If no ongoing response is observed, patients are removed from the study. All patients with massive mediastinal disease, regardless of stage, receive radiotherapy 2-3 weeks after completion of chemotherapy. * Arm B (Stanford V): Patients receive Stanford V chemotherapy comprising doxorubicin (25 mg/m²) and vinblastine (6 mg/m²) IV on day 1 of weeks 1, 3, 5, 7, 9, and 11; vincristine (1.4 mg/m²) and bleomycin (5 u/m²) IV on day 1 of weeks 2, 4, 6, 8, 10, and 12; mechlorethamine (6 mg/m²) IV on day 1 of weeks 1, 5, and 9 (if mechlorethamine is unavailable, may substitute with cyclophosphamide \[375 mg/m²\] IV); etoposide (60 mg/m²) IV on days 1 and 2 of weeks 3, 7, and 11; and oral prednisone (40 mg/m²) every other day of weeks 1-9 followed by a taper. All patients with bulky disease receive radiotherapy 2-3 weeks after completion of chemotherapy. Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 850 patients will be accrued for this study within 4.3 years.
Source references
references
  1. citation
    Gordon LI, Hong F, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Stiff PJ, Cheson BD, Gospodarowicz M, Advani R, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013 Feb 20;31(6):684-91. doi: 10.1200/JCO.2012.43.4803. Epub 2012 Nov 26.
    pmid
    23182987
    type
    RESULT
  2. citation
    Advani RH, Hong F, Fisher RI, Bartlett NL, Robinson KS, Gascoyne RD, Wagner H Jr, Stiff PJ, Cheson BD, Stewart DA, Gordon LI, Kahl BS, Friedberg JW, Blum KA, Habermann TM, Tuscano JM, Hoppe RT, Horning SJ. Randomized Phase III Trial Comparing ABVD Plus Radiotherapy With the Stanford V Regimen in Patients With Stages I or II Locally Extensive, Bulky Mediastinal Hodgkin Lymphoma: A Subset Analysis of the North American Intergroup E2496 Trial. J Clin Oncol. 2015 Jun 10;33(17):1936-42. doi: 10.1200/JCO.2014.57.8138. Epub 2015 Apr 20.
    pmid
    25897153
    type
    DERIVED
  3. citation
    Kanakry JA, Li H, Gellert LL, Lemas MV, Hsieh WS, Hong F, Tan KL, Gascoyne RD, Gordon LI, Fisher RI, Bartlett NL, Stiff P, Cheson BD, Advani R, Miller TP, Kahl BS, Horning SJ, Ambinder RF. Plasma Epstein-Barr virus DNA predicts outcome in advanced Hodgkin lymphoma: correlative analysis from a large North American cooperative group trial. Blood. 2013 May 2;121(18):3547-53. doi: 10.1182/blood-2012-09-454694. Epub 2013 Feb 5.
    pmid
    23386127
    type
    DERIVED
  4. citation
    Evens AM, Hong F, Gordon LI, Fisher RI, Bartlett NL, Connors JM, Gascoyne RD, Wagner H, Gospodarowicz M, Cheson BD, Stiff PJ, Advani R, Miller TP, Hoppe RT, Kahl BS, Horning SJ. The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. Br J Haematol. 2013 Apr;161(1):76-86. doi: 10.1111/bjh.12222. Epub 2013 Jan 29.
    pmid
    23356491
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        pective review documented the outcomes of patients aged 17 to 22 years treated in the Eastern Cooperative Oncology Group (ECOG) trials <a href="/clinicaltrials/NCT00003389">E2496 (NCT00003389)</a> or Stanford V versus the COG trial <a href="/clinicaltrials/NCT00025259">AHOD0031 (NCT00025259)</a>.[<a href="#cit/section_6.86">86</a
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        ented the outcomes of patients aged 17 to 22 years treated in the Eastern Cooperative Oncology Group (ECOG) trials <a href="/clinicaltrials/NCT00003389">E2496 (NCT00003389)</a> or Stanford V versus the COG trial <a href="/clinicaltrials/NCT00025259">AHOD0031 (NCT00025259)</a>.[<a href="#cit/section_6.86">86</a>][<a href="/Common/
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      source title
      Childhood Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 16, 2025
        datetime
        2025-04-16T12:00:00Z
        display
        April 16, 2025

    Preserved source evidence · Not medical advice