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

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.
 
ClinicalTrials.gov Identifier: NCT00003389
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : September 3, 2015
Last Update Posted : November 20, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group

Study Description
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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.


Condition or disease Intervention/treatment Phase
Lymphoma Drug: Doxorubicin Drug: Bleomycin Drug: Vinblastine Drug: Dacarbazine Drug: Vincristine Drug: Mechlorethamine Drug: Etoposide Drug: Prednisone Drug: Cyclophosphamide Radiation: Radiotherapy Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 854 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase III Trial of ABVD Versus Stanford V (+/-) Radiation Therapy in Locally Extensive and Advanced Stage Hodgkin's Disease
Study Start Date : April 1999
Actual Primary Completion Date : September 2011
Actual Study Completion Date : May 2016

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A (ABVD)
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.
 Drug: Doxorubicin
given IV
Other Names:
  • Adriamycin
  • Rubex
  • Adriamycin RDF
  • Adriamycin PFS
  • hydroxydaunorubicin
  • hydroxydaunomycin
  • ADR

Drug: Bleomycin
given IV
Other Names:
  • Blenoxane
  • BLM
  • Bleo

Drug: Vinblastine
given IV
Other Names:
  • Velban
  • vinblastine sulfate
  • vincaleukoblastine
  • VLB
  • Velsar
  • Alkaban AQ

Drug: Dacarbazine
given IV
Other Names:
  • DTIC
  • DTIC-Dome
  • DIC
  • imidazole carboxamide
  • dimethyl triazeno imidazole carboxamide

Radiation: Radiotherapy
Active Comparator: Arm B (Stanford V)
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.
 Drug: Doxorubicin
given IV
Other Names:
  • Adriamycin
  • Rubex
  • Adriamycin RDF
  • Adriamycin PFS
  • hydroxydaunorubicin
  • hydroxydaunomycin
  • ADR

Drug: Bleomycin
given IV
Other Names:
  • Blenoxane
  • BLM
  • Bleo

Drug: Vinblastine
given IV
Other Names:
  • Velban
  • vinblastine sulfate
  • vincaleukoblastine
  • VLB
  • Velsar
  • Alkaban AQ

Drug: Vincristine
given IV
Other Names:
  • Oncovin
  • Vincasar PFS
  • vincristine sulfate
  • VCR
  • leurocristine
  • LCR

Drug: Mechlorethamine
given IV
Other Names:
  • Mustargen
  • nitrogen mustard

Drug: Etoposide
given IV
Other Names:
  • VP-16
  • VePesid
  • VP-16-213
  • EPEG
  • epipodophyllotoxin

Drug: Prednisone
taken orally
Other Names:
  • Deltasone
  • Orasone
  • Medicorten
  • Panasol-S
  • Liquid-Pred

Drug: Cyclophosphamide
given IV
Other Names:
  • Cytoxan
  • Neosar
  • CTX
  • CPM

Radiation: Radiotherapy


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

    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.



Secondary Outcome Measures :
  1. 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 ]
    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.

  2. 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 ]
    Number of patients who developed second primary cancers


Eligibility Criteria
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Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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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): NCT00003389


Locations
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Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Study Chair: Sandra J. Horning, MD Stanford University
More Information
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Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00003389    
Other Study ID Numbers: CDR0000066386
E2496 ( Other Identifier: Eastern Cooperative Oncology Group (ECOG) )
U10CA021115 ( U.S. NIH Grant/Contract )
First Posted: January 27, 2003    Key Record Dates
Results First Posted: September 3, 2015
Last Update Posted: November 20, 2017
Last Verified: October 2017
Keywords provided by Eastern Cooperative Oncology Group:
stage I adult Hodgkin lymphoma
stage II adult Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
 adult lymphocyte depletion Hodgkin lymphoma
adult nodular sclerosis Hodgkin lymphoma
adult mixed cellularity Hodgkin lymphoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Prednisone
Cyclophosphamide
Dacarbazine
Mechlorethamine
Doxorubicin
Liposomal doxorubicin
Etoposide
Vincristine
 Etoposide phosphate
Bleomycin
Vinblastine
Podophyllotoxin
Imidazole
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic