Treating Young Patients With Newly Diagnosed, Low Stage, Lymphocyte Predominant Hodgkin Disease

PRIMARY OBJECTIVES:

I. To preserve the excellent cure rate in patients with lymphocyte predominant Hodgkin disease (LPHD) while employing a treatment strategy that minimizes the exposure to chemotherapy and radiation therapy in appropriate patients.

II. To estimate the proportion of stage I patients (with a single involved lymph node that is totally resected) who can be cured with surgery alone.

III. To estimate the proportions of stage I unresected, stage I resected (whose disease has recurred after observation), and stage II LPHD patients who can be cured with adriamycin (doxorubicin)/vincristine/prednisone/cyclophosphamide (AV-PC) x 3, with involved field radiation therapy (IFRT) for those who are not in a CR after chemotherapy.

IV. To reduce the potential for long-term toxicity of LPHD treatment.

OUTLINE: This is a pilot study.

Patients with stage IA disease who underwent confirmed complete resection of a single involved lymph node at diagnosis undergo observation only*.

Patients with stage IA disease who underwent possible complete resection of a single involved lymph node at diagnosis undergo imaging at 6-7 weeks after surgery. Patients with a confirmed complete resection by imaging undergo observation only*. Patients who do not demonstrate complete resection by imaging proceed to combination chemotherapy with or without radiotherapy.

Patients with stage IA disease who underwent a fine needle aspiration of a single involved lymph node OR an incomplete resection of a single involved lymph node at diagnosis may undergo a second surgery to achieve complete resection. Patients who undergo complete resection during the second surgery undergo imaging at 6-7 weeks after surgery. Patients with a confirmed complete resection by imaging undergo observation only*. Patients who do not undergo a second surgery OR do not achieve complete resection with the second surgery proceed to combination chemotherapy with or without radiotherapy. Patients with stage IA disease with involvement of more than 1 lymph node OR stage IIA disease proceed directly to combination chemotherapy with or without radiotherapy.

NOTE: *Patients with recurrent disease after observation only undergo biopsy and restaging and then proceed to combination chemotherapy with or without radiotherapy. (AS OF AMENDMENT #4, THE TREATMENT ARM FOR PATIENTS WHOSE CANCER RECURRED AFTER OBSERVATION ALONE IS NOW CLOSED)

COMBINATION CHEMOTHERAPY: Patients receive doxorubicin hydrochloride intravenously (IV) over 10-30 minutes and cyclophosphamide IV over 1 hour on day 1, vincristine IV over 1 minute on days 1 and 8, and prednisone orally (PO) or IV two or three times daily on days 1-7. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) after 3 courses of therapy proceed to follow-up. Patients who do not achieve a CR proceed to involved-field radiotherapy.

INVOLVED-FIELD RADIOTHERAPY (IFRT): Beginning within 3 weeks after completion of combination chemotherapy, patients undergo IFRT once daily, 5 days a week for 2.8 weeks (14 treatments).

Patients are followed every 3 months for 2 years, every 6 months for 3 years, annually for 5 years, and then every 5 years for 10 years.

Inclusion criteria

• Patients with newly diagnosed, previously untreated, biopsy-proven lymphocyte predominant Hodgkin disease (LPHD) are eligible for this protocol as follows:

• Diagnosis of LPHD must be made using the Revised European American Lymphoma (REAL)/World Health Organization (WHO) classification criteria and will be confirmed by rapid pathology central review
• Clinical stages as follows:

• Stage IA without bulk disease
• Stage IIA without bulk disease
• Patients with "B" symptoms or bulk disease are NOT eligible for this study
• Slides for rapid central pathology review must be sent to the Biopathology Center (BPC)
• Serum glutamic oxalo-acetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 times upper limit of normal (ULN)
• Total bilirubin =< 1.5 times ULN
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min
• Creatinine based on age/gender as follows:

• No greater than 0.4 mg/dL (for patients 1 to 5 months of age)
• No greater than 0.5 mg/dL (for patients 6 to 11 months of age)
• No greater than 0.6 mg/dL (for patients 1 year of age)
• No greater than 0.8 mg/dL (for patients 2 to 5 years of age)
• No greater than 1.0 mg/dL (for patients 6 to 9 years of age)
• No greater than 1.2 mg/dL (for patients 10 to 12 years of age)
• No greater than 1.4 mg/dL (for female patients >= 13 years of age)
• No greater than 1.5 mg/dL (for male patients 13 to 15 years of age)
• No greater than 1.7 mg/dL (for male patients >= 16 years of age)
• Shortening fraction of >= 27% by echocardiogram or ejection fraction of >= 50% by multigated radionuclide angiogram (MUGA)
• Lactating females must agree that they will not breastfeed a child if they are to receive chemotherapy or radiation treatment*
• Female patients of childbearing potential must have a negative pregnancy test if they are to receive chemotherapy or radiation treatment*
• Males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method if they are to receive chemotherapy or radiation treatment*
• Note: *Pregnant or breastfeeding women with stage I, single involved lymph node and confirmed (by Quality Assurance Review Center [QARC ]) total resection, are eligible for the observation arm only; no chemotherapy or radiation treatment will be administered to pregnant or breastfeeding women
• No prior chemotherapy
• More than 30 days since prior systemic corticosteroids
• No prior radiotherapy
• All patients and/or their parents or legal guardians must sign a written informed consent