This phase II trial is studying how well combination chemotherapy with or without radiation therapy works in treating young patients with favorable-risk Hodgkin lymphoma. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, mechlorethamine hydrochloride, vincristine sulfate, bleomycin, etoposide, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Radiation therapy uses high-energy x-rays to kill cancer cells for those patients that still had residual cancer at the end of chemotherapy. Giving combination chemotherapy with radiation therapy may kill more cancer cells and allow doctors to save the part of the body where the cancer started.
Patients receive doxorubicin hydrochloride intravenously (IV) and vinblastine IV on day 1 of weeks 1, 3, 5, and 7; mechlorethamine hydrochloride IV on day 1 of weeks 1 and 5; vincristine sulfate IV and bleomycin IV on day 1 of weeks 2, 4, 6, and 8; etoposide IV on day 1 of weeks 3 and 7; and prednisone orally (PO) three times daily every other day for 8 weeks. Two to 3 weeks after all chemotherapy is given, patients not achieving a complete response undergo radiation therapy to individual nodal sites (tailored fields). PRIMARY OBJECTIVES: 1\. To increase the complete response rate of favorable risk patients (excluding all patients with stage IA nodular lymphocyte predominant Hodgkin lymphoma) after 8 weeks Stanford V by at least 20% compared to favorable risk patients on HOD 99 after 8 weeks vincristine, doxorubicin hydrochloride, methotrexate and prednisone (VAMP). SECONDARY OBJECTIVES: 1. To estimate the disease failure rate within the radiation fields. 2. To examine patterns of treatment failure for children treated with low dose tailored field radiation therapy. 3. To describe acute hematologic and infectious toxicities as they relate to transfusion requirements, growth factor support, episodes of febrile neutropenia, and hospitalizations, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. 4. To compare the survival distributions (event-free and overall) and cumulative incidence of local failure and toxicities of favorable risk patients treated with 8 weeks of Stanford V chemotherapy and low-dose tailored-field radiation to those on the favorable risk group of the HOD 99 study that received VAMP and low-dose involved-field radiation. 5. To compare the survival distributions between patients that will not be prescribed radiotherapy after 8 weeks Stanford V and those patients on HOD 99 that did not receive radiotherapy after VAMP. 6. To estimate the event-free survival distributions of favorable risk patients treated with Stanford V chemotherapy alone and patients treated with Stanford V chemotherapy plus low dose tailored field radiation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
88
The Stanford V regimen is an abbreviated, multi-agent, dose-intensive regimen that utilizes many of the most active chemotherapy agents for Hodgkin lymphoma: Vinblastine, Doxorubicin, Vincristine, Bleomycin, Mechlorethamine, Etoposide, and Prednisone
Patients who achieve less than a complete response after 8 weeks of chemotherapy will receive 25.5 Gy to individual nodal sites (tailored fields) starting 2-3 weeks following completion of all chemotherapy and recovery of ANC to at least 1000.
Packard Children's Hospital, Stanford University
Palo Alto, California, United States
Rady Children's Hospital- San Diego
San Diego, California, United States
Children's Hospital of Illinois at OSF St. Francis Medical Center
Peoria, Illinois, United States
Maine Children's Cancer Program (MCCP)
Scarborough, Maine, United States
Dana-Farber Harvard Cancer Center
Boston, Massachusetts, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Complete Response Rate Estimate
To increase the complete response rate of favorable risk patients (excluding all patients with stage IA nodular lymphocyte predominant Hodgkin lymphoma) after 8 weeks Stanford V by at least 20% compared to favorable risk patients on HOD 99 after 8 weeks VAMP (NCT number: NCT00145600) .Complete response definition: Disappearance of all measurable or evaluable disease, signs, symptoms and biochemical changes related to the tumor. Biopsy confirmation is not mandatory. Residual PET-negative CT scan abnormalities representing \> 75% reduction (as measured by the product of 2 perpendicular diameters of lesions by CT or MR imaging) in the original tumor volume will be considered scar tissue without active tumor.
Time frame: 8 weeks
Acute Hematologic Toxicities
Description of acute hematologic toxicities as they relate to transfusion requirements, growth factor support, episodes of febrile neutropenia and hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The acute hematologic toxicities were summarized descriptively.
Time frame: 6 months
Acute Infectious Toxicities
Description of acute infectious toxicities as they relate to transfusion requirements, growth factor support, episodes of febrile neutropenia and hospitalizations, according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. The acute infectious toxicities were summarized descriptively.
Time frame: 6 months
Disease Failure Rate Within Radiation Fields
Defined as disease that recurs in the initially involved nodal region within the field of irradiation. The disease failure rate within the radiation fields will be estimated with a 95% confidence interval using appropriate methods (e.g., estimate cumulative incidence in the presence of competing risks).
Time frame: median 2 year post therapy
Treatment Failure Patterns for Children Treated With Tailored-field Radiation
Descriptive statistics related to local/distant failure will be produced. The cumulative incidence of local failure will be estimated and effects of prognostic factors will be examined. Effect of competing risks (distant failure, second malignancy and death) will be taken into account. Relapse rate within the radiation fields will be estimated and confidence interval will also be calculated.
Time frame: median 2 years post therapy
Prognostic Factors for Local Failure in Children Treated With Tailored-Field Radiation: Age
Age was examined for the association with cumulative incidence of local failure. Effect of competing risks (distant failure, second malignancy and death) will be taken into account. Fine and Gray's competing risk regression model with Wald test will be used to compute the p value for the statistical significance.
Time frame: median 2 years post therapy
Prognostic Factors for Local Failure in Children Treated With Tailored-Field Radiation: Gender
Gender was examined for the association with cumulative incidence of local failure. Effect of competing risks (distant failure, second malignancy and death) will be taken into account. Fine and Gray's competing risk regression model with Wald test will be used to compute the p value for the statistical significance.
Time frame: median 2 years post therapy
Prognostic Factors for Local Failure in Children Treated With Tailored-Field Radiation: Stage
Stage was examined for the association with cumulative incidence of local failure. Effect of competing risks (distant failure, second malignancy and death) will be taken into account. Fine and Gray's competing risk regression model with Wald test will be used to compute the p value for the statistical significance.
Time frame: median 2 years post therapy
Prognostic Factors for Local Failure in Children Treated With Tailored-Field Radiation: Histology
Histology was examined for its association with the cumulative incidence of local failure. Effect of competing risks (distant failure, second malignancy and death) will be taken into account. Fine and Gray's competing risk regression model with the Wald test will be used to compute the p-value for statistical significance.
Time frame: median 2 years post therapy
Comparison of Event-free and Overall Survival Distributions, and Cumulative Incidence of Local Failure of Patients Treated on This Study to Outcome in the Favorable Risk Group of HOD99
Log-rank tests are used to compare event-free survival and overall survival. Event-free survival is defined as time interval from the date of study enrollment to the date of first event (relapsed or progressive disease, second malignancy, or death from any cause) or to last follow-up for patients without events. Survival is defined as time interval from study enrollment to date of death from any cause or to date of last follow-up. Gray's test used to compare cumulative incidence of local failure between favorable risk patients treated on this protocol vs. treated on HOD99 and other regimens.
Time frame: median 2 years post therapy
Comparison of Toxicities of Patients Treated on This Study to Outcome and Toxicities in the Favorable Risk Group of HOD99
Comparison of the toxicities with grade \> 2 of low-risk patients treated with reduced duration Stanford V chemotherapy with or without low-dose tailored-field radiation (current HOD08 protocol) to those of favorable-risk patients on HOD99 (NCT00145600). Grading of toxicities for HOD08 and HOD99 used the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Time frame: median 2 years post therapy
Comparison of Event-free and Overall Survival Distributions and Cumulative Incidence of Local Failure Between Patients That Will Not be Prescribed Radiotherapy After 8 Weeks Stanford V and Those Patients on HOD99 That Received VAMP Without Radiotherapy
Log-rank tests are used to compare event-free survival and overall survival. Event-free survival is defined as time interval from the date of study enrollment to the date of first event (relapsed or progressive disease, second malignancy, or death from any cause) or to last follow-up for patients without events. Survival is defined as time interval from study enrollment to date of death from any cause or to date of last follow-up. Gray's test used to compare cumulative incidence of local failure between favorable risk patients treated on this protocol vs. treated on HOD99 and other regimens. Patients who will not be prescribed Radiotherapy in both protocols are those who achieved CR on the response assessment after chemotherapy.
Time frame: median 2 years post therapy
Event-free Survival Distributions of Favorable Risk Patients Treated With Stanford V Chemotherapy Alone and Patients Treated With Stanford V Chemotherapy Plus Low Dose Tailored-field Radiation
Event-free survival distributions of favorable risk patients treated with Stanford V chemotherapy alone and patients treated with Stanford V chemotherapy plus low dose tailored field radiation will be estimated by the Kaplan-Meier method.
Time frame: median 2 years post therapy
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