Lymphoma
Conditions
Keywords
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
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.
Interventions
DRUGDoxorubicin
given IV
DRUGBleomycin
given IV
DRUGVinblastine
given IV
DRUGDacarbazine
given IV
DRUGVincristine
given IV
DRUGMechlorethamine
given IV
DRUGEtoposide
given IV
DRUGPrednisone
taken orally
DRUGCyclophosphamide
given IV
RADIATIONRadiotherapy
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Failure-free Survival at 5 Years | 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
| Measure | Time frame | Description |
|---|---|---|
| 5-year Overall Survival | 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. |
| Incidence of Second Cancers | 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 |
Countries
Canada, South Africa, United States
Participant flow
Recruitment details
Between April 22, 1999 and June 15, 2006, 854 participants were enrolled. The first patient accrued was on June 17, 1999.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 395 |
| 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. | 399 |
| Total | 794 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 13 | 2 |
| Overall Study | Alternative therapy | 2 | 1 |
| Overall Study | Complicating disease | 1 | 0 |
| Overall Study | Death | 0 | 3 |
| Overall Study | Disease progression | 6 | 1 |
| Overall Study | Ineligible | 33 | 27 |
| Overall Study | Off-treatment reason missing | 31 | 21 |
| Overall Study | Withdrawal by Subject | 12 | 5 |
Baseline characteristics
| Characteristic | Arm B (Stanford V) | Total | Arm A (ABVD) |
|---|---|---|---|
| Age, Continuous | 33 years | 33 years | 33 years |
| Region of Enrollment Canada | 50 participants | 96 participants | 46 participants |
| Region of Enrollment United States | 349 participants | 698 participants | 349 participants |
| Sex: Female, Male Female | 182 Participants | 369 Participants | 187 Participants |
| Sex: Female, Male Male | 217 Participants | 425 Participants | 208 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 413 / 414 | 422 / 422 |
| serious Total, serious adverse events | 355 / 414 | 401 / 422 |
Outcome results
Primary
Failure-free Survival at 5 Years
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.
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
Population: Eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (ABVD) | Failure-free Survival at 5 Years | 0.74 Proportion of patients |
| Arm B (Stanford V) | Failure-free Survival at 5 Years | 0.71 Proportion of patients |
p-value: 0.32Log Rank
Secondary
5-year Overall Survival
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.
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
Population: Eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (ABVD) | 5-year Overall Survival | 0.88 Proportion of patients |
| Arm B (Stanford V) | 5-year Overall Survival | 0.88 Proportion of patients |
p-value: 0.86Log Rank
Secondary
Incidence of Second Cancers
Number of patients who developed second primary 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A (ABVD) | Incidence of Second Cancers | 15 participants |
| Arm B (Stanford V) | Incidence of Second Cancers | 19 participants |