Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy Followed by Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	21 and under	NCI	COG-AHOD0431 AHOD0431, NCT00302003

Objectives

1. Investigate the paradigm of response-based therapy for low-risk Hodgkin's lymphoma by eliminating involved-field radiotherapy (IFRT) in patients who achieve a complete remission (CR) after initial chemotherapy.
2. Investigate whether 3 courses of doxorubicin hydrochloride, vincristine, prednisone, and cyclophosphamide (AV-PC) for the treatment of low-risk Hodgkin's lymphoma is sufficient to induce CR in at least 80% of patients.
3. Investigate whether patients who experience a low-risk relapse after initial treatment with chemotherapy alone can be successfully treated with a salvage regimen comprising ifosfamide and vinorelbine ditartrate with dexamethasone, etoposide phosphate, cisplatin, and cytarabine (IV/DECA) and IFRT.
4. Maintain the overall survival for patients with low-risk Hodgkin's lymphoma at or above 97%.
5. Determine the prognostic significance of very early response as measured by fludeoxyglucose-positron emission tomography (FDG-PET) or gallium after the first course of chemotherapy.
6. Evaluate the prognostic significance of elevation of erythrocyte sedimentation rate and C-reactive protein at the time of diagnosis in patients with low-risk Hodgkin's lymphoma on CR rate and relapse rate after chemotherapy alone.
7. Determine the frequency and severity of late effects of therapy, including thyroid dysfunction, infertility, cardiotoxicity, and second malignant neoplasms.

Entry Criteria

Disease Characteristics:

• Histologically confirmed Hodgkin's lymphoma meeting the following criteria:
  • Newly diagnosed disease
  • Stage IA OR stage IIA without bulky disease
    • Bulky disease is defined as a large mediastinal mass or large extramediastinal nodal aggregate
  • No lymphocyte-predominant histology

Prior/Concurrent Therapy:

• No prior chemotherapy or radiotherapy
• At least 30 days since prior systemic corticosteroids
• No other concurrent cancer chemotherapy or immunomodulating agents (including steroids)
• No concurrent corticosteroid therapy

Patient Characteristics:

• Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
• Bilirubin ≤ 1.5 times normal
• ALT ≤ 2.5 times normal
• Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by MUGA
• No pathologic prolongation of QTc interval on 12-lead ECG
• Not pregnant or nursing
• Fertile patients must use effective contraception
• Negative pregnancy test

Expected Enrollment

A total of 400 patients will be accrued for this study.

Outcomes

Minimum time to a requirement for involved-field radiotherapy (IFRT), requirement for additional chemotherapy and IFRT for retrieval, occurrence of a second malignant neoplasm, or death from any cause
Minimum time to a relapse of higher risk at any time, any relapse following treatment with protocol-mandated IFRT, death from any cause, or the occurrence of a second malignant neoplasm
Minimum time to a relapse of any kind, death from any cause, or occurrence of a second malignant neoplasm

Time to death

Outline

This is a multicenter study.

• Initial chemotherapy: Patients receive doxorubicin hydrochloride IV over 10-30 minutes and cyclophosphamide IV over 1 hour on days 1-2, vincristine IV on days 1 and 8, oral prednisone on days 1-7, and filgrastim (G-CSF) subcutaneously (SC) on days 3-7 and 9-14. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission (CR) proceed to observation. Patients achieving partial remission proceed to radiotherapy. Patients who have a low-risk relapse after achieving CR on initial chemotherapy proceed to salvage chemotherapy followed by radiotherapy. Patients who have stable disease or disease progression go off study.



• Salvage chemotherapy: Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1-5, and G-CSF SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients then receive dexamethasone IV over 15 minutes every 12 hours, etoposide phosphate IV over 3 hours every 12 hours, and cytarabine IV over 3 hours every 12 hours on days 1 and 2; cisplatin IV over 6 hours on day 1; and G-CSF SC or IV beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses. Patients then proceed to radiotherapy.



• Involved-field radiotherapy (IFRT): Beginning 4 weeks after completion of chemotherapy, patients undergo IFRT once daily, 5 days a week, for 2.8 weeks. Patients who do not achieve CR go off study.

After completion of study treatment, patients are followed periodically for up to 10 years.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Frank Keller, MD, Protocol chair		Ph: 304-293-1217; 877-427-2894

Registry Information
Official Title		A Phase III Study for the Treatment of Children and Adolescents With Newly Diagnosed Low Risk Hodgkin's Disease
Trial Start Date		2006-02-13
Trial Completion Date		2009-02-07 (estimated)
Registered in ClinicalTrials.gov		NCT00302003
Date Submitted to PDQ		2005-11-16
Information Last Verified		2009-04-03
NCI Grant/Contract Number		CA98543