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

Reduced Duration Stanford V Chemotherapy With or Without Low-Dose Tailored-Field Radiation Therapy For Favorable Risk Pediatric Hodgkin Lymphoma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hodgkin Lymphoma
• Intervention / Treatment: Drug: Stanford V Chemotherapy; Radiation: Radiation Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94304
      • Packard Children's Hospital, Stanford University
    • San Diego, California, United States, 92123
      • Rady Children's Hospital- San Diego
  • Illinois
    • Peoria, Illinois, United States, 61637
      • Children's Hospital of Illinois at OSF St. Francis Medical Center
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Children's Cancer Program (MCCP)
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Harvard Cancer Center
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment; 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)

Drug: Stanford V Chemotherapy; 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; Radiation: Radiation Therapy; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	median 2 years post therapy
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.	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.	6 months
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.	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.	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.	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.	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.	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.	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.	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.	median 2 years post therapy

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Investigators: Principal Investigator: Matt Ehrhardt, MD, MS, St. Jude Children's Research Hospital

Publications and helpful links

General Publications

• Flerlage JE, Feraco AM, Zhou Y, Zheng Y, Liang J, Lucas JT Jr, Friedmann AM, Weinstein HJ, Yock TI, Shulkin B, Kaste SC, Marks LJ, Ehrhardt MJ, Dixon SB, Howard S, de Alarcon P, Luna-Fineman S, Geddis A, Larsen EC, Marcus K, Billett AL, Donaldson SS, Hudson MM, Metzger ML, Krasin MJ, Link MP. Dose-dense chemotherapy enables elimination of RT for the majority of low-risk pediatric Hodgkin lymphomas: PHC study HOD08. Blood. 2026 Mar 19;147(12):1289-1301. doi: 10.1182/blood.2025029535.

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2009
• Primary Completion (Actual): January 11, 2019
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: February 17, 2009
• First Submitted That Met QC Criteria: February 18, 2009
• First Posted (Estimated): February 19, 2009

Study Record Updates

• Last Update Posted (Actual): May 26, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hemic and Lymphatic Diseases; Hodgkin Disease; Therapeutics; Radiotherapy
• Other Study ID Numbers: HOD08; NCI-2009-01138 (Registry Identifier: NCI's Clinical Trial Reporting Program)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No