Combination Chemotherapy With or Without Radiation Therapy in Treating Young Patients With Favorable-Risk Hodgkin Lymphoma

Phase 2

Active, not recruiting

Conditions: Hodgkin Lymphoma

Interventions: Drug: Stanford V Chemotherapy
Radiation: Radiation Therapy

Registration Number: NCT00846742

Lead Sponsor: St. Jude Children's Research Hospital

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 88

Inclusion Criteria

Histologically confirmed, previously untreated Hodgkin lymphoma.
Age: Participants must be 21 years of age or younger
Stage must be classified as one of the following:

Ann Arbor stage IA or IIA with:

Non-bulky mediastinal disease (< 33% mediastinal to thoracic ratio on CXR)
< 3 nodal regions involved on the same side of the diaphragm
No "E" lesion
Female patients who are post-menarchal must have a negative pregnancy test. Patients of reproductive potential must agree to use an effective contraceptive method.
Signed informed consent
If re-evaluation of a patient's disease shows intermediate risk features, the patient will be removed from the HOD08.

Exclusion Criteria

Intermediate or High risk disease, defined as Stage IB, any III or IV or IA/IIA with "E" lesion(s), 3 or more nodal sites involved, or bulky mediastinal adenopathy

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Stanford V Chemotherapy	Participants receive Stanford V Chemotherapy with or without radiation therapy. Patients receive doxorubicin hydrochloride 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 of weeks 1-8. Beginning 2-3 weeks after completion of chemotherapy, patients not achieving complete response undergo radiation therapy to individual nodal sites (tailored fields)
Treatment	Radiation Therapy	Participants receive Stanford V Chemotherapy with or without radiation therapy. Patients receive doxorubicin hydrochloride 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 of weeks 1-8. Beginning 2-3 weeks after completion of chemotherapy, patients not achieving complete response undergo radiation therapy to individual nodal sites (tailored fields)

Primary Outcome Measures

Name	Time	Method
Complete Response Rate Estimate	8 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Acute Hematologic Toxicities	6 months	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.
Acute Infectious Toxicities	6 months	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.
Disease Failure Rate Within Radiation Fields	median 2 year post therapy	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).
Treatment Failure Patterns for Children Treated With Tailored-field Radiation	median 2 years post therapy	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.
Prognostic Factors for Local Failure in Children Treated With Tailored-Field Radiation: Age	median 2 years post therapy	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.
Prognostic Factors for Local Failure in Children Treated With Tailored-Field Radiation: Gender	median 2 years post therapy	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.
Prognostic Factors for Local Failure in Children Treated With Tailored-Field Radiation: Stage	median 2 years post therapy	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.
Prognostic Factors for Local Failure in Children Treated With Tailored-Field Radiation: Histology	median 2 years post therapy	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.
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	median 2 years post therapy	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.
Comparison of Toxicities of Patients Treated on This Study to Outcome and Toxicities in the Favorable Risk Group of HOD99	median 2 years post therapy	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.
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	median 2 years post therapy	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.
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	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 will be estimated by the Kaplan-Meier method.

Trial Locations

Locations (6): Packard Children's Hospital, Stanford University
🇺🇸
Palo Alto, California, United States
Rady Children's Hospital- San Diego
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San Diego, California, United States
St. Jude Children's Research Hospital
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Memphis, Tennessee, United States
Children's Hospital of Illinois at OSF St. Francis Medical Center
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Peoria, Illinois, United States
Dana-Farber Harvard Cancer Center
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Boston, Massachusetts, United States
Maine Children's Cancer Program (MCCP)
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Scarborough, Maine, United States