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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:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
NCT00003389
First received: November 1, 1999
Last updated: September 25, 2015
Last verified: September 2015
  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 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 Intervention Phase
Lymphoma
Drug: Doxorubicin
Drug: Bleomycin
Drug: Vinblastine
Drug: Dacarbazine
Drug: Vincristine
Drug: Mechlorethamine
Drug: Etoposide
Drug: Prednisone
Drug: Cyclophosphamide
Radiation: Radiotherapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    Number of patients who developed second primary cancers


Enrollment: 854
Study Start Date: April 1999
Estimated Study Completion Date: May 2016
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   16 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003389

  Show 539 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Investigators
Study Chair: Sandra J. Horning, MD Stanford University
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00003389     History of Changes
Other Study ID Numbers: CDR0000066386  E2496  U10CA021115 
Study First Received: November 1, 1999
Results First Received: August 5, 2015
Last Updated: September 25, 2015
Health Authority: United States: Federal Government

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:
Mechlorethamine
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Dacarbazine
Liposomal doxorubicin
Etoposide phosphate
Doxorubicin
Prednisone
Etoposide
Vincristine
Vinblastine
Bleomycin
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

ClinicalTrials.gov processed this record on September 27, 2016