Hodgkin Disease, Lymphoma, Lymphoma: Hodgkin, Lymphoma, Hodgkin Disease
Conditions
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 tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: This phase 2 trial is studying how well giving combination chemotherapy together with low-dose radiation therapy works in treating patients with stage I or stage IIA Hodgkin's lymphoma.
Detailed description
OBJECTIVES: * Evaluate the freedom from progression in patients with stage I or IIA Hodgkin's lymphoma with a favorable prognosis treated with Stanford V-C chemotherapy comprising cyclophosphamide, doxorubicin, vinblastine, prednisone, vincristine, bleomycin, and etoposide with low-dose radiotherapy (RT). * Minimize the early and late effects of treatment in these patients by avoiding staging laparotomy and its consequences, limiting cumulative doses of chemotherapy, and reducing the dose of RT to moderately bulky sites of disease. * Assess early and late treatment-related toxicity, freedom from second disease progression, and overall survival at 5 and 10 years in patients treated with this regimen. Participants receive Stanford V-C chemotherapy comprising cyclophosphamide IV over 30 to 60 minutes weekly on weeks 1 and 5; doxorubicin IV and vinblastine IV over 5 minutes once weekly on weeks 1, 3, 5, and 7; oral prednisone every other day on weeks 1 to 8; vincristine IV, and bleomycin IV over 5 minutes once weekly on weeks 2, 4, 6, and 8; and etoposide IV over 60 minutes on days 1 and 2 of weeks 3 and 7. Prior to protocol amendment, participants were assigned to treatment on the basis of tumor size (\< 5 cm vs 5 to 10 cm), with only the participants with larger tumors receiving RT. Beginning 2 to 3 weeks after completion of chemotherapy, participants in the +RT group will receive low-dose radiotherapy 5 days a week for approximately 3 weeks. Subsequent to amendment, all participants received RT. Participants are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Interventions
DRUGVincristine
1.4 mg/m² intravenously (IV) on week 2, 4, 6, 8
DRUGCyclophosphamide
650 mg/m², on week 1 and 5
DRUGDoxorubicin
25 mg/m², on week 1, 3, 5, 7
DRUGPrednisone
40 mg/m², oral, every other day. Taper-reduction 10 mg/m² every other day during last 2 weeks of chemotherapy
DRUGBleomycin
5 u/m² intravenously (IV) on week 2, 4, 6, 8
DRUGEtoposide
60 mg/m² x 2 intravenously (IV) on week 3, 7 (d 15, 16, 43, 44)
RADIATIONLow-dose radiotherapy (RT)
20 Grey (Gy) modified involved field radiotherapy administered as consolidative irradiation will beginning between 2 and 12 weeks after the completion of Stanford V-C chemotherapy regimen.
Sponsors
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients with tumors 5 to 10 cm were to be assigned to concurrent radiotherapy, and participants with tumors less than 5 cm were initially planned to not receive radiotherapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of previously untreated stage I or IIA Hodgkin's lymphoma, eligible subtypes * Nodular sclerosis * Mixed cellularity * Classical, not otherwise specified * Age ≥ 18 years and ≤ 70 years * Granulocytes ≥ 2 x 10e6/µL * Platelets ≥ 150 x 10e6/µL * Bilirubin ≤ 2.5 mg/dL * Serum creatinine ≤ 2 mg/dL * Patients \> 50 years or those with a history of cardiac disease should have an ejection fraction ≥ 50% * All scans, X-rays, laboratory tests must be performed within 6 weeks of enrollment * Pathologic material reviewed at Stanford University * Evaluation by Stanford Medical Oncology and Radiation Oncology with review at the Hodgkin's Disease Staging Conference * Written informed consent
Exclusion criteria
* Lymphocytic predominance Hodgkin's disease * Prior treatment for Hodgkin's disease * Mediastinal mass equal to or greater than one-third the maximum intrathoracic diameter on a standing posteroanterior chest x-ray * Any lymph node mass \> 10 cm in greatest trans-axial diameter * Two or more extranodal sites of disease * Constitutional (B) symptoms present at diagnosis * Prior or concurrent malignancies within 5 years (EXCEPTION: basal cell carcinoma of the skin) * Any medical contraindication to the planned treatment, including: * Pregnant * Positive antibody test for the human immunodeficiency virus (HIV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | up to 3 years | Progression-free survival was assessed for 3 years from the completion of treatment. Progression-free survival was considered to mean the proportion of patients (percentage) still alive without disease recurrence or progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early Treatment-related Toxicity | Within 30 days of treatment | Early treatment-related toxicity was assessed as the number of treatment-related, non-serious adverse events that occurred during treatment or within 30 days of the completion of treatment. |
| Late Treatment-related Toxicity | 16 years | Late treatment-related toxicity was assessed as the overall number of late-appearing toxicities (ie, related adverse events, after treatment completion) including but not limited to diagnosis of a 2nd cancer; hypothyroidism; infertility; pulmonary toxicity; or cardiac toxicity, at up to 16 years from date of diagnosis. |
| Frequency of Complete Response | 5 weeks | The frequency of complete response (CR) is reported as the number (proportion) of subjects in complete response, as assessed during weeks 4 to 5 of chemotherapy. Per protocol, CR is defined as complete regression of all palpable and radiographic demonstrable disease by computed tomography (CT) scan or positron emission tomography-CT (PET-CT). |
| Overall Survival (OS) | 16 years | Overall survival was assessed at up to 16 years from date of diagnosis, and reported as the median years of survival with standard deviation. |
| Survival at 5 and 10 Years | 5 and 10 years | Survival at 5 and 10 years is expressed at the percentage of subjects known to remain alive at those timepoints. |
| Second Hodgkin's Disease Progression | 16 years | Second Hodgkin's disease progression is reported as the number of participants experiencing 2 instances of progression of the underlying Hodgkin's disease, assessed at up to 16 years from date of diagnosis. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Stanford V-C + Low-dose Radiotherapy Stanford V-C = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide.
* Vincristine: 1.4 mg/m² intravenously (IV) on week 2, 4, 6, 8
* Cyclophosphamide: 650 mg/m², on week 1 and 5
* Doxorubicin: 25 mg/m², on week 1, 3, 5, 7
* Prednisone: 40 mg/m², oral, every other day. Taper-reduction 10 mg/m² mg every other day during last 2 weeks of chemotherapy
* Bleomycin: 5 u/m² intravenously (IV) on week 2, 4, 6, 8
* Etoposide: 60 mg/m² x 2 intravenously (IV) on week 3, 7 (d 15, 16, 43, 44)
Low-dose radiotherapy (RT) = 20 Grey (Gy) modified involved field radiotherapy administered as consolidative irradiation will beginning between 2 and 12 weeks after the completion of Stanford V-C chemotherapy regimen. | 72 |
| Stanford V-C Only Stanford V-C = Vinblastine, cyclophosphamide, doxorubicin, prednisone, bleomycin, + etoposide.
* Vincristine: 1.4 mg/m² intravenously (IV) on week 2, 4, 6, 8
* Cyclophosphamide: 650 mg/m², on week 1 and 5
* Doxorubicin: 25 mg/m², on week 1, 3, 5, 7
* Prednisone: 40 mg/m², oral, every other day. Taper-reduction 10 mg/m² mg every other day during last 2 weeks of chemotherapy
* Bleomycin: 5 u/m² intravenously (IV) on week 2, 4, 6, 8
* Etoposide: 60 mg/m² x 2 intravenously (IV) on week 3, 7 (d 15, 16, 43, 44) | 4 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Complications of auto accident | 1 | 0 |
Baseline characteristics
| Characteristic | Stanford V-C + Low-dose Radiotherapy | Stanford V-C Only | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 70 Participants | 4 Participants | 74 Participants |
| Region of Enrollment United States | 72 participants | 4 participants | 76 participants |
| Sex: Female, Male Female | 43 Participants | 2 Participants | 45 Participants |
| Sex: Female, Male Male | 29 Participants | 2 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 72 | 0 / 4 |
| other Total, other adverse events | 72 / 72 | 4 / 4 |
| serious Total, serious adverse events | 25 / 72 | 2 / 4 |
Outcome results
Primary
Progression-free Survival (PFS)
Progression-free survival was assessed for 3 years from the completion of treatment. Progression-free survival was considered to mean the proportion of patients (percentage) still alive without disease recurrence or progression.
Time frame: up to 3 years
Population: Does not include those participants whose treatment was significantly modified due to accidental injury; or who were lost-to-follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stanford V-C + Low-dose Radiotherapy | Progression-free Survival (PFS) | 89.7 percentage of participants |
| Stanford V-C Only | Progression-free Survival (PFS) | 50 percentage of participants |
Secondary
Early Treatment-related Toxicity
Early treatment-related toxicity was assessed as the number of treatment-related, non-serious adverse events that occurred during treatment or within 30 days of the completion of treatment.
Time frame: Within 30 days of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stanford V-C + Low-dose Radiotherapy | Early Treatment-related Toxicity | 422 treatment-related adverse events |
| Stanford V-C Only | Early Treatment-related Toxicity | 24 treatment-related adverse events |
Secondary
Frequency of Complete Response
The frequency of complete response (CR) is reported as the number (proportion) of subjects in complete response, as assessed during weeks 4 to 5 of chemotherapy. Per protocol, CR is defined as complete regression of all palpable and radiographic demonstrable disease by computed tomography (CT) scan or positron emission tomography-CT (PET-CT).
Time frame: 5 weeks
Population: Participants, for whom a PET-CT scan was not conducted in week 4 to 5 of treatment, were not included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stanford V-C + Low-dose Radiotherapy | Frequency of Complete Response | 31 Participants |
Secondary
Late Treatment-related Toxicity
Late treatment-related toxicity was assessed as the overall number of late-appearing toxicities (ie, related adverse events, after treatment completion) including but not limited to diagnosis of a 2nd cancer; hypothyroidism; infertility; pulmonary toxicity; or cardiac toxicity, at up to 16 years from date of diagnosis.
Time frame: 16 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stanford V-C + Low-dose Radiotherapy | Late Treatment-related Toxicity | Second Cancer | 2 treatment-related adverse events |
| Stanford V-C + Low-dose Radiotherapy | Late Treatment-related Toxicity | Hypothyroidism | 19 treatment-related adverse events |
| Stanford V-C Only | Late Treatment-related Toxicity | Second Cancer | 0 treatment-related adverse events |
| Stanford V-C Only | Late Treatment-related Toxicity | Hypothyroidism | 0 treatment-related adverse events |
Secondary
Overall Survival (OS)
Overall survival was assessed at up to 16 years from date of diagnosis, and reported as the median years of survival with standard deviation.
Time frame: 16 years
Population: Includes all participants, except those whose treatment was significantly modified due to accidental injury. Subjects who became lost-to-follow-up were censored at their last known value.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stanford V-C + Low-dose Radiotherapy | Overall Survival (OS) | 10.4 years |
| Stanford V-C Only | Overall Survival (OS) | 13.2 years |
Secondary
Second Hodgkin's Disease Progression
Second Hodgkin's disease progression is reported as the number of participants experiencing 2 instances of progression of the underlying Hodgkin's disease, assessed at up to 16 years from date of diagnosis.
Time frame: 16 years
Population: Data to confirm Hodgkin's disease 2nd progression was not available for some participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Stanford V-C + Low-dose Radiotherapy | Second Hodgkin's Disease Progression | 3 Participants |
| Stanford V-C Only | Second Hodgkin's Disease Progression | 1 Participants |
Secondary
Survival at 5 and 10 Years
Survival at 5 and 10 years is expressed at the percentage of subjects known to remain alive at those timepoints.
Time frame: 5 and 10 years
Population: For overall survival at 5 and 10 years, this analysis does not include those participants known to be alive, but whose diagnosis was less than 5 or 10 years prior to current date or last date known alive, respectively.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Stanford V-C + Low-dose Radiotherapy | Survival at 5 and 10 Years | 5 years | 67 Participants |
| Stanford V-C + Low-dose Radiotherapy | Survival at 5 and 10 Years | 10 years | 41 Participants |
| Stanford V-C Only | Survival at 5 and 10 Years | 5 years | 3 Participants |
| Stanford V-C Only | Survival at 5 and 10 Years | 10 years | 3 Participants |