Therapy for Pediatric Hodgkin Lymphoma

• Patient Quality of Life (QoL) [ Time Frame: At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy. ] [ Designated as safety issue: No ]
  Patient QOL will be measured at multiple time points to assess the patient's physical emotional, social, and school functioning.
• Parent Proxy Quality of Life (QoL) [ Time Frame: At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy. ] [ Designated as safety issue: No ]
  Parent's assessment of child's physical, emotional, social, and school functioning over multiple time points.
• Correlation of Agreement Between Patient QoL and Parent Proxy QoL at Multiple Time Points. [ Time Frame: At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy. ] [ Designated as safety issue: No ]
  Assess and compare the patient reported and parent proxy quality of life across multiple time points.
• Symptom Distress [ Time Frame: At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy. ] [ Designated as safety issue: No ]
  The patient's degree of discomfort from specific treatment-related symptoms i.e., nausea, sleep disturbances, appetite, etc. across multiple time points.
• Correlation Between QoL and Symptom Distress [ Time Frame: At Diagnosis (T1), completion of 2 cycles of chemotherapy (T2), completion of 4 cycles of chemotherapy (T3), completion of radiation (T4), and 3-6 months (T5) after the completion of therapy. ] [ Designated as safety issue: No ]
  Assess the relationship between quality of life and symptom distress across multiple time points.

With the success of current chemotherapy for Hodgkin's disease, the goal of this protocol is to maintain the currently successful cure rate and reduce treatment related side effects and long term toxicity. The main purpose of this study is to estimate the event free survival of patients treated with risk-adapted therapy compared to historical controls.

This study will evaluate the following objectives:

Primary Objectives:

1. To evaluate the efficacy of 4 cycles of VAMP chemotherapy alone in patients with favorable risk Hodgkin's disease who achieve a complete response after 2 cycles of VAMP chemotherapy.
2. To evaluate the efficacy of 4 cycles VAMP chemotherapy plus low dose RT in patients with favorable risk Hodgkin's disease who achieve a partial response after 2 cycles of VAMP chemotherapy.
3. To evaluate the efficacy of 2 alternating cycles of VAMP/COP chemotherapy (total 4 cycles of chemotherapy) plus low-dose, involved-field RT in children with intermediate risk Hodgkin's disease.
4. To evaluate the efficacy of 12 weeks of Stanford V chemotherapy plus low-dose, involved-field RT in children with unfavorable risk Hodgkin's disease.

Secondary Objectives:

1. To evaluate patient quality of life during and after treatment from the patient and parent perspective.
2. To compare patient and parental ratings of treatment-related symptoms and patient physical, psychological, social and cognitive functioning before the first treatment (T1 - baseline); after Cycle 2 or after 8 weeks of Stanford V (T2 - Evaluate Response); after cycle 4 or after 12 weeks of Stanford V and before or on the first day of radiation (as applicable) (T3); at the conclusion of radiation or within a few days following the end of radiation (as applicable) (T4); and at 3 to 6 months after completion of therapy follow-up evaluation (T5).

• Drug: 12 Week Stanford V Chemotherapy
  12 weeks of Stanford V chemotherapy plus low-dose, involved-field RT in children
• Drug: 4 cycles of VAMP chemotherapy
  4 cycles of VAMP chemotherapy alone in patients who achieve a complete response after 2 cycles of VAMP chemotherapy. For patients that do not achieve a complete response after 2 cycles of VAMP, they will receive low low-dose involved field radiotherapy at the end of all chemotherapy.
• Drug: 2 alternating cycles of VAMP/COP chemotherapy
  2 alternating cycles of VAMP/COP chemotherapy (total 4 cycles of chemotherapy) plus low-dose, involved-field RT.
• Drug: 3 alternating cycles of VAMP/COP chemotherapy
  3 alternating cycles of VAMP/COP chemotherapy (total 6 cycles of chemotherapy) plus low-dose, involved-field RT

• Experimental: Unfavorable Risk, Group 2
  Unfavorable risk (group 2) arm in patients with Hodgkin's disease (n=146)
  Intervention: Drug: 12 Week Stanford V Chemotherapy
• Experimental: Favorable Risk
  Favorable Risk arm in patients with Hodgkin's Disease (n=91).
  Intervention: Drug: 4 cycles of VAMP chemotherapy
• Experimental: Intermediate Risk
  Intermediate Arm in patients with Hodgkins's disease (n=46).
  Intervention: Drug: 2 alternating cycles of VAMP/COP chemotherapy
• Experimental: Unfavorable Risk, Group 1
  Unfavorable risk group 1 closed early due to excessive number of adverse events (n=13).
  Intervention: Drug: 3 alternating cycles of VAMP/COP chemotherapy

General Eligibility Criteria:

1. Eligible patients must have histologically confirmed previously untreated Hodgkin's disease (Patients receiving limited emergent RT or steroid therapy because of cardiopulmonary decompensation or spinal cord compression will be eligible for protocol enrollment).
2. Patients must be 21 years of age or younger
3. Ann Arbor stages IIB-IV
4. No prior treatment.
5. No pregnant or lactating women.
6. Signed informed consent
7. If re-evaluation of a patient's disease shows favorable risk features or intermediate risk features, the patient will be removed from the HOD99 study and consented to the respective HOD08 or HOD05 study.

Eligibility for treatment of favorable risk features:

1. Ann Arbor stage IA or IIA with:

1. Non-bulky mediastinal disease (<33% mediastinal to thoracic ratio on chest x-ray)
2. < 3 nodal regions involved on the same side of the diaphragm
3. No "E" lesion

Eligibility for treatment of intermediate risk features:

1. Stage must be classified as one of the following:

1. Ann Arbor stage IB and IIIA
2. Ann Arbor stage IA or IIA with ANY of the following features: (1) "E" lesion(s), (2) 3 or more nodal sites involved, (3) Bulky mediastinal adenopathy (mediastinal mass to thoracic cavity ratio 33% or greater by chest radiograph)

Eligibility of unfavorable risk features:

1. Stage must be classified as one of the following:

a. Ann Arbor stage IIB, IIIB, or any IV