Symptoms and General Pathology

All Conditions

Neoplasms

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Sclerosis

Lymphoma

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Hodgkin Lymphoma

microarray analysis

protein expression analysis

immunohistochemistry staining method

laboratory biomarker analysis

Frank G. Keller, MD

RATIONALE: Studying samples of tissue from patients with cancer in the laboratory may help doctors identify and learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment.

PURPOSE: This research trial is studying protein biomarker levels in tissue samples from young patients with low-risk Hodgkin lymphoma.

OBJECTIVES:

* To investigate the variability of expression of human geminal-center-associated lymphoma (HGAL) protein in pediatric low-risk Hodgkin lymphoma.
* To assess the variability of HGAL staining between risk groups by comparing samples from subjects enrolled in the low-risk study AHOD0431 with subject samples enrolled in AHOD0031 for intermediate-risk classical Hodgkin Lymphoma (cHL).
* To assess the variability of HGAL staining by evaluating a tissue array created from subjects with intermediate-risk cHL.
* To correlate rapid or slow early-response in the intermediate-risk group with HGAL protein expression.

OUTLINE: Paraffin-embedded tissue samples and tissue microarrays are analyzed for protein expression by IHC.

Protein Biomarker Levels in Tissue Samples From Young Patients With Low-risk Hodgkin Lymphoma

Investigation to Evaluate the Levels of Human Germinal-center-Associated Lymphoma (HGAL) Protein in Pediatric Hodgkin Lymphoma and Correlate With Early Response

National Cancer Institute (NCI)

Children's Oncology Group

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Etoposide

Vinorelbine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Vincristine

Ifosfamide

Lenograstim

Etoposide phosphate

Bleomycin

Isophosphamide mustard

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Patients receive 2 more courses of ABVE-PC comprising doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2; bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8; etoposide IV over 1-2 hours on days 1-3; oral prednisone twice daily on days 1-7; and filgrastim SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.

Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-10 minutes on days 1 and 5, and filgrastim SC or IV beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.

All patients receive ABVE-PC induction therapy then they are assigned to Group 2 (RER), Group 3 (SER) or taken off study if they develop progressive disease.

bleomycin sulfate

doxorubicin hydrochloride

liposomal vincristine sulfate

vinorelbine tartrate

cyclophosphamide

etoposide phosphate

prednisone

filgrastim

ifosfamide

Kara Kelly, MD

This phase III trial is studying how well giving combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed Hodgkin lymphoma. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x-rays to kill cancer cells. Giving combination chemotherapy together with radiation therapy may kill more cancer cells.

PRIMARY OBJECTIVES:

I. To maintain the overall survival (as defined by 4-year "second-event" free survival) for subjects with high risk Hodgkin lymphoma at or above 95%.

SECONDARY OBJECTIVES:

I. To maintain 3-year event-free survival for subjects with high risk Hodgkin lymphoma at or above 93%.

II. To maintain comparable overall survival (as defined by 4-year "second-event" free survival) between subjects with high risk Hodgkin lymphoma who have a rapid or slow response to the initial 2 cycles of ABVE-PC\* by intensifying therapy through the addition of 2 cycles of ifosfamide/vinorelbine in those with a slow early response.

III. To investigate whether very early response assessment measured by FDG-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.

IV. To describe the patterns of relapse after ABVE-PC\* and risk-adapted radiotherapy.

OUTLINE: This is a multicenter study.

INDUCTION THERAPY (ABVE-PC): Patients receive doxorubicin hydrochloride IV over 1-120 minutes and cyclophosphamide IV over 30-60 minutes on days 1 and 2, bleomycin sulfate IV over at least 10 minutes or subcutaneously (SC) and vincristine sulfate IV on days 1 and 8, etoposide phosphate IV over 1-2 hours on days 1-3, oral prednisone twice daily on days 1-7, and filgrastim\* SC or IV daily beginning on day 4 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression.

NOTE: \*Patients do not receive filgrastim on day 8.

Patients undergo clinical restaging and response assessment after 2 courses of induction therapy. Patients with rapid early response (RER) or slow early response (SER) proceed to consolidation therapy. Patients with progressive disease go off study.

CONSOLIDATION THERAPY: Patients are assigned to 1 of 2 consolidation therapy regimens based on response to induction therapy. Patients who develop progressive disease after induction are taken off protocol therapy.

REGIMEN I (RER): Patients receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.

REGIMEN II (SER): Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-30 minutes on days 1 and 5, and filgrastim SC or IV daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.

Patients with a continued response after completion of consolidation therapy proceed to risk-adapted radiotherapy.

RISK-ADAPTED RADIOTHERAPY: Beginning at 3 weeks after completion of consolidation chemotherapy, patients undergo radiotherapy once daily, 5 days a week, for 3 weeks (14 fractions) in the absence of unacceptable toxicity or disease progression. Patients classified as RER receive radiation therapy only to sites of bulky disease. Patients classified as SER receive radiation therapy to sites of bulky disease and areas that remain FDG-PET avid after induction therapy.

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

Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma

A Non-Randomized Phase III Study of Response Adapted Therapy for the Treatment of Children With Newly Diagnosed High Risk Hodgkin Lymphoma

Second event here is defined as any relapse/progression of Hodgkin Lymphoma (HL) or a previously reported second malignant neoplasm (SMN), a new SMN, or death after a first event which can be relapse/progression of HL, SMN, biopsy-proven HL following completion of Consolidation for Slow Early Response (SER) patient, positive bilateral bone marrow biopsy following completion of Consolidation for Stage IV patient, or death. If death occurs as the 1st event, it also counts as the 2nd event.

The primary endpoint for safety analysis and monitoring is toxic death, which is death primarily attributable to treatment.

Survival from enrollment to first event: relapse/progression, second malignancy, or death.

To investigate whether very early response assessment measured by Fluorodeoxyglucose-PET after 1 cycle of chemotherapy identifies a subject cohort that can be studied in future trials and that is distinguishable from currently defined RER after 2 cycles.

A description, survival to relapse, of patterns of relapse after Doxorubicin, Bleomycin, Vincristine, Etoposide - Prednisone, Cyclophosphamide (ABVE-PC) and risk-adapted radiotherapy.

The number of patients that experience Common Terminology Criteria (CTC) Version 4 grade 3 or higher non-hematologic toxicity at any time during protocol therapy.

Group 1 includes all patients and the Adverse Event reports of all events across the treatment procedure. Patients who experienced induction only are also included in Group 1. After induction patients were assigned to Group 2 (RER) and Group 3 (SER). While Group 2 and Group 3 are mutually exclusive, they are subsets of Group 1. Hence the Adverse Events in Group 1 will have overlaps with Adverse Events in Group 2 and Group 3.

Group 1

Group 2

Group 3

INDUCTION THERAPY (ABVE-PC)

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Canada

United States

Australia

Puerto Rico

Region of Enrollment

Results Reporting Coordinator

This analysis excludes n=20 patients who had protocol early terminations or deviations (n=4 Regimen I, n=12 Regimen II, and n=4 Induction only).

Second-event-free Survival

The six patients who received induction and reported death. The analysis here examines whether their death is primarily attributable to treatment or not.

Safety Analysis and Monitoring of Toxic Death

164 Group 1 All Patients received induction therapy.

Event Free Survival

Group 4

Group 5

RER with positive PET-1, Event-Free Survival for RER PET-1 positive patients is compared to that of RER with negative PET-1: n=57 PET-1 positive RER patients, compared to 2 events among n=20 PET-1 negative RER patients. Two PET-1 equivocal RER patients (1 with relapse and 1 censored) are not included in this analysis.

Event-free Survival for Rapid Early Response (RER) Positron Emission Tomography(PET)-1 Positive, RER PET-1 Negative

Group 6

Group 7

161 patients began consolidation therapy: 126 patients received risk-adapted radiotherapy after consolidation therapy ABVE-PC and 35 did not.

Relapse-free Survival

161 patients began consolidation therapy: 81 Group 2 Regimen I and 80 Group 3 Regimen II.

Grade 3 and 4 Non-hematologic Toxicities During Protocol Therapy

164 Group 1 All Patients received induction therapy. 161 patients began consolidation therapy: 81 Group 2 Regimen I and 80 Group 3 Regimen II.

Overall Survival

Patients receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.

REGIMEN I (RER)

Patients receive ifosfamide IV continuously on days 1-4, vinorelbine ditartrate IV over 6-30 minutes on days 1 and 5, and filgrastim SC or IV daily beginning on day 6 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of unacceptable toxicity or disease progression. Patients then receive 2 more courses of ABVE-PC in the absence of unacceptable toxicity or disease progression.

REGIMEN II (SER)

Induction

Consolidation Maintenance

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Prednisolone

Methylprednisolone

Vinblastine

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

watch and wait strategy after complete resection of localised (e.g. Stage IA) nodular lymphocyte-predominant HL

3 cycles of intensity-reduced, anthracycline-free chemotherapy (Cyclophosphamide, vinblastine and prednisone)

prednisolone

vinblastine sulfate

watchful waiting

therapeutic conventional surgery

Dieter Koerholz, MD

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, vinblastine, and prednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Surgery to remove involved lymph nodes may be an effective treatment for young patients with nodular lymphocyte-predominant Hodgkin lymphoma.

PURPOSE: This phase IV trial is continuing to study the side effects of giving surgery alone or giving surgery with cyclophosphamide, vinblastine, and prednisolone compared with giving cyclophosphamide, vinblastine, and prednisolone alone in treating young patients with stage IA or stage IIA nodular lymphocyte-predominant Hodgkin lymphoma.

OBJECTIVES:

Primary

* Determine the 5-year event-free survival of children or adolescents with stage IA or IIA nodular lymphocyte-predominant Hodgkin lymphoma treated with surgery alone or with cyclophosphamide, vinblastine, and prednisolone.

Secondary

* Determine if this regimen results in a decrease in overall survival rates, in significant upstaging at relapse, or increased rates of histological transformation in these patients.

OUTLINE:

* Group 1 (patients with stage IA disease only): Patients undergo surgical resection of the involved lymph nodes. Patients who achieve complete resection then enter follow-up (watch and wait); patients who do not achieve complete resection enters group 2 treatment.
* Group 2 (patients with stage IIA disease or incompletely resected stage IA disease): Patients receive cyclophosphamide, vinblastine, and prednisolone for 3 courses. Patients with good response enter follow-up (watch and wait). Patients without a good response are taken off protocol.

After completion of study treatment, patients are followed-up periodically.

Surgery Alone or With CYC VBL and PRED or CVP Alone in Stage IA or IIA Nodular Lymphocyte-Predominant Hodgkin Lymphoma

First International Inter-Group Study for Nodular Lymphocyte-Predominant Hodgkin's Lymphoma in Children and Adolescents

Time from treatment start until relapse/progression, secondary malignancy or death

Stage greater than IIA at relapse diagnosis

Evaluation of AEs, SAEs atc. according to CTC

Deutsche Krebshilfe e.V., Bonn (Germany)

Euronet Worldwide

Christine Mauz-Körholz

Prof. Dr. Christine Mauz-Körholz

Pharmaceutical Solutions

Dermatologic Agents

Dexamethasone

Cytarabine

Ophthalmic Solutions

Cisplatin

Dexamethasone acetate

BB 1101

Podophyllotoxin

Cortisone

Ichthammol

Antimetabolites

Antiviral Agents

Adjuvants, Immunologic

HIV Protease Inhibitors

Protease Inhibitors

Keratolytic Agents

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease.

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR undergo IFRT approximately 3 weeks after the last day of ABVE course 4.

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR are randomized to receive no further treatment.

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with VGPR, PR or SD undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week.

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients with PD are taken off therapy.

Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, and cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy.

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive 2 additional courses of ABVE-PC. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy.

Bleomycin Sulfate

Doxorubicin Hydrochloride

Filgrastim

Involved-Field Radiation Therapy

Vincristine Sulfate Liposome

Debra Friedman

This randomized phase III trial is studying different chemotherapy regimens given with or without radiation therapy to compare how well they work in treating children with newly diagnosed Hodgkin's disease. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more cancer cells. Radiation therapy uses high-energy x-rays to damage cancer cells. It is not yet known if chemotherapy is more effective with or without additional chemotherapy and/or radiation therapy in treating Hodgkin's disease.

OBJECTIVES:

I. To compare response-based therapy to standard therapy for intermediate risk Hodgkin disease.

II. To determine whether involved field radiation therapy (IFRT) can be eliminated based upon early and complete response to multiagent chemotherapy.

III. To determine whether the addition of an additional two cycles of chemotherapy (DECA) can improve outcome in those with a slow early response to standard chemotherapy.

IV. To prospectively collect information on the individual prognostic significance of the following presenting factors: erythrocyte sedimentation rate, circulating levels of IL-10, each of the "B" symptoms - fever, night sweats, weight loss, nodal aggregate \> 6 cm, large mediastinal mass \> 1/3 thoracic diameter and number of involved nodal sites, histology, albumin, blood counts, sex and age.

V. To study the reliability and utility of \[18F\] -Fluorodeoxyglucose (FDG) Imaging (PET scans) as an imaging modality in Hodgkin disease.

VI. To determine the frequency and severity of late effects of therapy including thyroid dysfunction, infertility, cardiotoxicity, pulmonary toxicity and second malignant neoplasms.

VII. To serve as the therapeutic companion to biology studies in Hodgkin disease and correlate those results with response to therapy, event free-survival and overall survival.

OUTLINE: This is a randomized, multicenter study.

ARM I (ALL PATIENTS-OFF THERAPY BEFORE CALLBACK-INDUCTION CHEMOTHERAPY \[ABVE-PC\]): Patients receive doxorubicin intravenously (IV) over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or subcutaneously (SC) and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. At the end of initial chemotherapy, patients undergo evaluation for response. Patients with less than 60% disease reduction are considered to have slow early response (SER). Patients with 60% or more disease reduction are considered to have rapid early response (RER).

RER: Patients receive 2 additional courses of ABVE-PC chemotherapy. After completion of treatment, patients are randomized to 1 of 4 treatment arms.

ARM II: Patients with sustained complete response (CR) undergo involved field radiation therapy (IFRT) approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week.

ARM III: Patients with sustained CR receive no further treatment.

ARM IV: Patients with very good partial response (VGPR), partial response (PR) or stable disease (SD) undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week.

ARM V: Patients with progressive disease are taken off therapy and treated their physician's discretion.

SER: Patients are randomized to 1 of 2 treatment arms.

ARM VI: Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, cytarabine IV over 3 hours on days 1-2, and receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 and 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 and G-CSF SC beginning on day 3 and continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. After these 2 courses, patients then receive 2 additional courses of ABVE-PC chemotherapy.

ARM VII: Patients receive 2 courses of ABVE-PC chemotherapy.

In both SER arms, patients with sustained CR or PR undergo IFRT approximately 3 weeks after the last course of chemotherapy.

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

Chemotherapy With or Without Additional Chemotherapy and/or Radiation Therapy in Treating Children With Newly Diagnosed Hodgkin's Disease

A Phase III Groupwide Study of Dose-Intensive Response-Based Chemotherapy and Radiation Therapy for Children and Adolescents With Newly Diagnosed Intermediate Risk Hodgkin Disease

Probability of event-Free survival which is defined as the time from study entry to treatment failure (disease progression, disease recurrence, biopsy positive residual after completion of all protocol therapy), occurrence of a second malignant neoplasm, or death from any cause. Patients without report of such events where censored at last contact.

Number of participants with complete response and very good partial response at the end of protocol therapy.

Occurrence of any grade 4 non-hematologic toxicity or grade 3 non-hematologic toxicity which doesn't respond to treatment within 7 days despite recommended therapy modification, or toxic death, which is any death primarily attributable to treatment. Grade 3 is defined to be severe or medically significant but not immediate life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 refers to toxicities with life-threatening consequences; urgent intervention indicated.

Probability of overall survival which is defined as the time from study entry to death from any cause. Patients alive where censored at last contact.

Serious AE:

Eligible participants are analyzed and ineligible participants (n=22) are excluded from Arms I (n=14), II (n=1), III (n=0), IV (n=6), V (n=0), VI (n=1), and VII (n=0).

Other AE:

Eligible participants are analyzed and ineligible participants (n=22) are excluded from Arms I (n=14), II (n=1), III (n=0), IV (n=6), V (n=0), VI (n=1), and VII (n=0).

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin sulfate IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, oral prednisone 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease.

Bleomycin Sulfate: Given IV or SC

Cyclophosphamide: Given IV

Doxorubicin Hydrochloride: Given IV

Etoposide: Given IV

Filgrastim: Given SC

Prednisone: Given orally

Vincristine Sulfate Liposome: Given IV

Arm I (Patients Off-therapy Before Callback-Induction Only)

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR undergo IFRT approximately 3 weeks after the last day of ABVE course 4.

Bleomycin Sulfate: Given IV or SC

Cyclophosphamide: Given IV

Doxorubicin Hydrochloride: Given IV

Etoposide: Given IV

Filgrastim: Given SC

Involved-Field Radiation Therapy: Undergo IFRT

Prednisone: Given orally

Vincristine Sulfate Liposome: Given IV

Arm II (RER With CR [ABVE-PC, IFRT])

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with sustained CR are randomized to receive no further treatment.

Bleomycin Sulfate: Given IV or SC

Cyclophosphamide: Given IV

Doxorubicin Hydrochloride: Given IV

Etoposide: Given IV

Filgrastim: Given SC

Prednisone: Given orally

Vincristine Sulfate Liposome: Given IV

Arm III (RER With CR [ABVE-PC])

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive an additional 2 courses of ABVE-PC. Patients with VGPR, PR or SD undergo IFRT approximately 3 weeks after the last day of ABVE-PC course 4 for 5 days a week.

Bleomycin Sulfate: Given IV or SC

Cyclophosphamide: Given IV

Doxorubicin Hydrochloride: Given IV

Etoposide: Given IV

Filgrastim: Given SC

Involved-Field Radiation Therapy: Undergo IFRT

Prednisone: Given orally

Vincristine Sulfate Liposome: Given IV

Arm IV (RER With Less Than CR [ABVE-PC, IFRT])

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients with PD are taken off therapy.

Bleomycin Sulfate: Given IV or SC

Cyclophosphamide: Given IV

Doxorubicin Hydrochloride: Given IV

Etoposide: Given IV

Filgrastim: Given SC

Prednisone: Given orally

Vincristine Sulfate Liposome: Given IV

Arm V (RER With PD)

Patients receive dexamethasone IV over 15 minutes, etoposide IV over 3 hours, \& cytarabine IV over 3 hours on days 1-2. Patients receive 2 drops of dexamethasone ophthalmic solution every 6 hours on days 1, 2 \& 3. Patients also receive cisplatin PO or IV over 12 hours as pre-hydration followed by continuous IV over 6 hours on day 1 \& G-CSF SC beginning on day 3 \& continuing until blood counts recover. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then receive 2 additional courses of ABVE-PC chemotherapy. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy.

Bleomycin Sulfate: Given IV or SC

Cisplatin: Given IV

Cyclophosphamide: Given IV

Cytarabine: Given IV

Dexamethasone: Given IV

Doxorubicin Hydrochloride: Given IV

Etoposide: Given IV

Filgrastim: Given SC

Involved-Field Radiation Therapy: Undergo IFRT

Pre

Arm VI (SER [DECA, ABVE-PC, IFRT])

Patients receive doxorubicin IV over 10-30 minutes on days 1-2, bleomycin IV over 10-20 minutes or SC and vincristine IV on days 1 and 8, etoposide IV over 1 hour on days 1-3, prednisone PO 2 or 3 times daily on days 1-7, and cyclophosphamide IV over 1 hour on day 1. Patients receive filgrastim (G-CSF) SC beginning on day 2 and continuing until blood counts recover (G-CSF is held on day 8). Treatment repeats every 21 days for 2 courses in the absence of progressive disease. Patients receive 2 additional courses of ABVE-PC. Patients with sustained complete or partial response undergo IFRT approximately 3 weeks after the last course of chemotherapy.

Bleomycin Sulfate: Given IV or SC

Cyclophosphamide: Given IV

Doxorubicin Hydrochloride: Given IV

Etoposide: Given IV

Filgrastim: Given SC

Involved-Field Radiation Therapy: Undergo IFRT

Prednisone: Given orally

Vincristine Sulfate Liposome: Given IV

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Protein Biomarker Levels in Tissue Samples From Young Patients With Low-risk Hodgkin Lymphoma	NCT01366157	Lymphoma	microarray anal... protein express... immunohistochem... laboratory biom...	- 21 Years	Children's Oncology Group
Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma	NCT01026220	Childhood Nodul... Stage III Child... Stage IV Childh...	bleomycin sulfa... doxorubicin hyd... liposomal vincr... vinorelbine tar... cyclophosphamid... etoposide phosp... prednisone filgrastim ifosfamide	- 21 Years	Children's Oncology Group
Surgery Alone or With CYC VBL and PRED or CVP Alone in Stage IA or IIA Nodular Lymphocyte-Predominant Hodgkin Lymphoma	NCT01088750	Lymphoma	cyclophosphamid... prednisolone vinblastine sul... watchful waitin... therapeutic con...	- 17 Years	Martin-Luther-Universität Halle-Wittenberg
Combination Chemotherapy and Radiation Therapy in Treating Young Patients With Newly Diagnosed Hodgkin Lymphoma	NCT01026220	Childhood Nodul... Stage III Child... Stage IV Childh...	bleomycin sulfa... doxorubicin hyd... liposomal vincr... vinorelbine tar... cyclophosphamid... etoposide phosp... prednisone filgrastim ifosfamide	- 21 Years	Children's Oncology Group
Protein Biomarker Levels in Tissue Samples From Young Patients With Low-risk Hodgkin Lymphoma	NCT01366157	Lymphoma	microarray anal... protein express... immunohistochem... laboratory biom...	- 21 Years	Children's Oncology Group
Chemotherapy With or Without Additional Chemotherapy and/or Radiation Therapy in Treating Children With Newly Diagnosed Hodgkin's Disease	NCT00025259	Childhood Lymph... Childhood Mixed... Childhood Nodul... Childhood Nodul... Stage I Childho... Stage II Childh... Stage III Child... Stage IV Childh...	Bleomycin Sulfa... Cisplatin Cyclophosphamid... Cytarabine Dexamethasone Doxorubicin Hyd... Etoposide Filgrastim Involved-Field ... Prednisone Vincristine Sul...	- 21 Years	Children's Oncology Group

Spots Global Cancer Trial Database for childhood nodular lymphocyte predominant hodgkin lymphoma