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

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00025259

Collaborator

National Cancer Institute (NCI) (NIH)

1,734

Enrollment

175

Locations

Arms

9.9

Patients Per Site

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Childhood Lymphocyte-Depleted Classical Hodgkin Lymphoma Childhood Mixed Cellularity Classical Hodgkin Lymphoma Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma Childhood Nodular Sclerosis Classical Hodgkin Lymphoma Stage I Childhood Hodgkin Lymphoma Stage II Childhood Hodgkin Lymphoma Stage III Childhood Hodgkin Lymphoma Stage IV Childhood Hodgkin Lymphoma	Biological: Bleomycin Sulfate Drug: Cisplatin Drug: Cyclophosphamide Drug: Cytarabine Drug: Dexamethasone Drug: Doxorubicin Hydrochloride Drug: Etoposide Biological: Filgrastim Radiation: Involved-Field Radiation Therapy Drug: Prednisone Drug: Vincristine Sulfate Liposome	Phase 3

Detailed Description

OBJECTIVES:

To compare response-based therapy to standard therapy for intermediate risk Hodgkin disease.
To determine whether involved field radiation therapy (IFRT) can be eliminated based upon early and complete response to multiagent chemotherapy.
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.
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.
To study the reliability and utility of [18F] -Fluorodeoxyglucose (FDG) Imaging (PET scans) as an imaging modality in Hodgkin disease.
To determine the frequency and severity of late effects of therapy including thyroid dysfunction, infertility, cardiotoxicity, pulmonary toxicity and second malignant neoplasms.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1734 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2002

Actual Primary Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (Patients off-therapy before callback-Induction only) 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.	Biological: Bleomycin Sulfate Given IV or SC Other Names: Blanoxan BleMomycine Blenoxane Bleo-cell Bleo-S Bleocin Bleolem Bleomycin Sulfas Bleomycin Sulphate Blexane Oil Bleo Drug: Cyclophosphamide Given IV Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Drug: Doxorubicin Hydrochloride Given IV Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex Drug: Etoposide Given IV Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 Biological: Filgrastim Given SC Other Names: Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim Drug: Prednisone Given orally Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone Drug: Vincristine Sulfate Liposome Given IV Other Names: Marqibo
Experimental: 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 undergo IFRT approximately 3 weeks after the last day of ABVE course 4.	Biological: Bleomycin Sulfate Given IV or SC Other Names: Blanoxan BleMomycine Blenoxane Bleo-cell Bleo-S Bleocin Bleolem Bleomycin Sulfas Bleomycin Sulphate Blexane Oil Bleo Drug: Cyclophosphamide Given IV Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Drug: Doxorubicin Hydrochloride Given IV Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex Drug: Etoposide Given IV Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 Biological: Filgrastim Given SC Other Names: Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim Radiation: Involved-Field Radiation Therapy Undergo IFRT Other Names: IFRT Involved field radiotherapy Drug: Prednisone Given orally Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone Drug: Vincristine Sulfate Liposome Given IV Other Names: Marqibo
Experimental: 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 sustained CR are randomized to receive no further treatment.	Biological: Bleomycin Sulfate Given IV or SC Other Names: Blanoxan BleMomycine Blenoxane Bleo-cell Bleo-S Bleocin Bleolem Bleomycin Sulfas Bleomycin Sulphate Blexane Oil Bleo Drug: Cyclophosphamide Given IV Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Drug: Doxorubicin Hydrochloride Given IV Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex Drug: Etoposide Given IV Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 Biological: Filgrastim Given SC Other Names: Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim Drug: Prednisone Given orally Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone Drug: Vincristine Sulfate Liposome Given IV Other Names: Marqibo
Experimental: 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 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.	Biological: Bleomycin Sulfate Given IV or SC Other Names: Blanoxan BleMomycine Blenoxane Bleo-cell Bleo-S Bleocin Bleolem Bleomycin Sulfas Bleomycin Sulphate Blexane Oil Bleo Drug: Cyclophosphamide Given IV Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Drug: Doxorubicin Hydrochloride Given IV Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex Drug: Etoposide Given IV Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 Biological: Filgrastim Given SC Other Names: Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim Radiation: Involved-Field Radiation Therapy Undergo IFRT Other Names: IFRT Involved field radiotherapy Drug: Prednisone Given orally Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone Drug: Vincristine Sulfate Liposome Given IV Other Names: Marqibo
Experimental: Arm V (RER with PD) 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.	Biological: Bleomycin Sulfate Given IV or SC Other Names: Blanoxan BleMomycine Blenoxane Bleo-cell Bleo-S Bleocin Bleolem Bleomycin Sulfas Bleomycin Sulphate Blexane Oil Bleo Drug: Cyclophosphamide Given IV Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Drug: Doxorubicin Hydrochloride Given IV Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex Drug: Etoposide Given IV Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 Biological: Filgrastim Given SC Other Names: Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim Drug: Prednisone Given orally Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone Drug: Vincristine Sulfate Liposome Given IV Other Names: Marqibo
Experimental: Arm VI (SER [DECA, ABVE-PC, IFRT]) 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.	Biological: Bleomycin Sulfate Given IV or SC Other Names: Blanoxan BleMomycine Blenoxane Bleo-cell Bleo-S Bleocin Bleolem Bleomycin Sulfas Bleomycin Sulphate Blexane Oil Bleo Drug: Cisplatin Given IV Other Names: Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin Drug: Cyclophosphamide Given IV Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Drug: Cytarabine Given IV Other Names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta-D-arabinofuranosylcytosine 1.beta.-D-Arabinofuranosylcytosine 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl- 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl- Alexan Ara-C ARA-cell Arabine Arabinofuranosylcytosine Arabinosylcytosine Aracytidine Aracytin Aracytine Beta-Cytosine Arabinoside CHX-3311 Cytarabinum Cytarbel Cytosar Cytosar-U Cytosine Arabinoside Cytosine-.beta.-arabinoside Cytosine-beta-arabinoside Erpalfa Starasid Tarabine PFS U 19920 U-19920 Udicil WR-28453 Drug: Dexamethasone Given IV Other Names: Aacidexam Adexone Aknichthol Dexa Alba-Dex Alin Alin Depot Alin Oftalmico Amplidermis Anemul mono Auricularum Auxiloson Baycuten Baycuten N Cortidexason Cortisumman Decacort Decadrol Decadron Decalix Decameth Decasone R.p. Dectancyl Dekacort Deltafluorene Deronil Desamethasone Desameton Dexa-Mamallet Dexa-Rhinosan Dexa-Scheroson Dexa-sine Dexacortal Dexacortin Dexafarma Dexafluorene Dexalocal Dexamecortin Dexameth Dexamethasonum Dexamonozon Dexapos Dexinoral Dexone Dinormon Fluorodelta Fortecortin Gammacorten Hexadecadrol Hexadrol Lokalison-F Loverine Methylfluorprednisolone Millicorten Mymethasone Orgadrone Spersadex Visumetazone Drug: Doxorubicin Hydrochloride Given IV Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex Drug: Etoposide Given IV Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 Biological: Filgrastim Given SC Other Names: Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim Radiation: Involved-Field Radiation Therapy Undergo IFRT Other Names: IFRT Involved field radiotherapy Drug: Prednisone Given orally Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone Drug: Vincristine Sulfate Liposome Given IV Other Names: Marqibo
Experimental: Arm VII (SER [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.	Biological: Bleomycin Sulfate Given IV or SC Other Names: Blanoxan BleMomycine Blenoxane Bleo-cell Bleo-S Bleocin Bleolem Bleomycin Sulfas Bleomycin Sulphate Blexane Oil Bleo Drug: Cyclophosphamide Given IV Other Names: (-)-Cyclophosphamide 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cyclostine Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan Neosar Revimmune Syklofosfamid WR- 138719 Drug: Doxorubicin Hydrochloride Given IV Other Names: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex Drug: Etoposide Given IV Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 Biological: Filgrastim Given SC Other Names: Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim Radiation: Involved-Field Radiation Therapy Undergo IFRT Other Names: IFRT Involved field radiotherapy Drug: Prednisone Given orally Other Names: .delta.1-Cortisone 1, 2-Dehydrocortisone Adasone Cortancyl Dacortin DeCortin Decortisyl Decorton Delta 1-Cortisone Delta-Dome Deltacortene Deltacortisone Deltadehydrocortisone Deltasone Deltison Deltra Econosone Lisacort Meprosona-F Metacortandracin Meticorten Ofisolona Orasone Panafcort Panasol-S Paracort PRED Predicor Predicorten Prednicen-M Prednicort Prednidib Prednilonga Predniment Prednisonum Prednitone Promifen Servisone SK-Prednisone Drug: Vincristine Sulfate Liposome Given IV Other Names: Marqibo

Outcome Measures

Primary Outcome Measures

Event-free Survival [5 years]
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.

Secondary Outcome Measures

Disease Response Assessed by Modified RECIST Criteria [Protocol therapy: the overall duration of which is: (n=1527) an average of 137.1 days, median 133.0 days, interquartile range: 101.0, 164.0 days.]
Number of participants with complete response and very good partial response at the end of protocol therapy.
Grade 3 or 4 Non-hematologic Toxicity [Protocol therapy: the overall duration of which is: (n=1684) an average of 137.3 days, median 133.0 days, interquartile range: 101.0, 164.0 days.]
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.
Overall Survival [5 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with newly diagnosed, pathologically confirmed Hodgkin disease (all histologies) are eligible for this protocol if they meet the following clinical stage guidelines:
All Stage IB regardless of bulk disease
All Stage IIB regardless of bulk disease
Stage IA only with bulk disease
Stage IIA only with bulk disease
All Stage IAE, IIAE regardless of bulk disease
All Stage IIIA, IIIAE, IIIAS, IIIAE+S regardless of bulk disease
All Stage IVA, IVAE regardless of bulk disease
May not be staged by laparotomy alone
Surgically staged patients must also have presurgical staging
Bilirubin no greater than 1.5 times normal
SGOT or SGPT less than 2.5 times normal
Creatinine no greater than 1.5 times normal
Creatinine clearance greater than 40 mL/min
Radioisotope glomerular filtration rate greater than 70 mL/min
Shortening fraction at least 27% by echocardiogram
Ejection fraction at least 50% by MUGA
No pathologic prolongation of QTc interval on 12-lead electrocardiogram
FEV_1/FVC greater than 60% by pulmonary function test
Pulse oximetry greater than 94%
No evidence of dyspnea at rest
No exercise intolerance
Adequate venous access
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No prior chemotherapy
At least 1 month since prior corticosteroids except prednisone for respiratory distress
No prior radiotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Southern California Permanente Medical Group	Downey	California	United States	90242
5	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
6	Loma Linda University Medical Center	Loma Linda	California	United States	92354
7	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
8	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
9	David Geffen School of Medicine at UCLA	Los Angeles	California	United States	90095
10	Children's Hospital Central California	Madera	California	United States	93636-8762
11	Kaiser Permanente-Oakland	Oakland	California	United States	94611
12	Children's Hospital of Orange County	Orange	California	United States	92868
13	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
14	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
15	Santa Barbara Cottage Hospital	Santa Barbara	California	United States	93102
16	Children's Hospital Colorado	Aurora	Colorado	United States	80045
17	Yale University	New Haven	Connecticut	United States	06520
18	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
19	Children's National Medical Center	Washington	District of Columbia	United States	20010
20	Broward Health Medical Center	Fort Lauderdale	Florida	United States	33316
21	Lee Memorial Health System	Fort Myers	Florida	United States	33901
22	University of Florida	Gainesville	Florida	United States	32610
23	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
24	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
25	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
26	Nicklaus Children's Hospital	Miami	Florida	United States	33155
27	Baptist Hospital of Miami	Miami	Florida	United States	33176
28	Florida Hospital Orlando	Orlando	Florida	United States	32803
29	Nemours Children's Clinic - Orlando	Orlando	Florida	United States	32806
30	All Children's Hospital	Saint Petersburg	Florida	United States	33701
31	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida	United States	33607
32	Saint Mary's Hospital	West Palm Beach	Florida	United States	33407
33	Georgia Regents University Medical Center	Augusta	Georgia	United States	30912
34	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
35	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
36	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
37	University of Illinois	Chicago	Illinois	United States	60612
38	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
39	Loyola University Medical Center	Maywood	Illinois	United States	60153
40	Advocate Lutheran General Hospital	Park Ridge	Illinois	United States	60068
41	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
42	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
43	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
44	Blank Children's Hospital	Des Moines	Iowa	United States	50309
45	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
46	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
47	Kosair Children's Hospital	Louisville	Kentucky	United States	40202
48	Tulane University Health Sciences Center	New Orleans	Louisiana	United States	70112
49	Children's Hospital New Orleans	New Orleans	Louisiana	United States	70118
50	Eastern Maine Medical Center	Bangor	Maine	United States	04401
51	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
52	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
53	Baystate Medical Center	Springfield	Massachusetts	United States	01199
54	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
55	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
56	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
57	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
58	Michigan State University Clinical Center	East Lansing	Michigan	United States	48824-7016
59	Hurley Medical Center	Flint	Michigan	United States	48502
60	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan	United States	49008
61	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
62	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
63	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota	United States	55455
64	Mayo Clinic	Rochester	Minnesota	United States	55905
65	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
66	University of Missouri - Ellis Fischel	Columbia	Missouri	United States	65212
67	The Childrens Mercy Hospital	Kansas City	Missouri	United States	64108
68	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri	United States	63104
69	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
70	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
71	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
72	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
73	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
74	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
75	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
76	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
77	Saint Joseph's Regional Medical Center	Paterson	New Jersey	United States	07503
78	Overlook Hospital	Summit	New Jersey	United States	07902
79	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
80	Albany Medical Center	Albany	New York	United States	12208
81	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490
82	Brooklyn Hospital Center	Brooklyn	New York	United States	11201
83	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
84	Winthrop University Hospital	Mineola	New York	United States	11501
85	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
86	Mount Sinai Medical Center	New York	New York	United States	10029
87	Columbia University/Herbert Irving Cancer Center	New York	New York	United States	10032
88	Weill Medical College of Cornell University	New York	New York	United States	10065
89	University of Rochester	Rochester	New York	United States	14642
90	Stony Brook University Medical Center	Stony Brook	New York	United States	11794
91	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
92	New York Medical College	Valhalla	New York	United States	10595
93	Mission Hospital-Memorial Campus	Asheville	North Carolina	United States	28801
94	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
95	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
96	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
97	Duke University Medical Center	Durham	North Carolina	United States	27710
98	East Carolina University	Greenville	North Carolina	United States	27858
99	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
100	Sanford Medical Center-Fargo	Fargo	North Dakota	United States	58122
101	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
102	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
103	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
104	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
105	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
106	Dayton Children's Hospital	Dayton	Ohio	United States	45404
107	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
108	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
109	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma	United States	74136
110	Legacy Emanuel Hospital and Health Center	Portland	Oregon	United States	97227
111	Oregon Health and Science University	Portland	Oregon	United States	97239
112	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
113	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
114	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
115	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134
116	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
117	Rhode Island Hospital	Providence	Rhode Island	United States	02903
118	Medical University of South Carolina	Charleston	South Carolina	United States	29425
119	Palmetto Health Richland	Columbia	South Carolina	United States	29203
120	Greenville Cancer Treatment Center	Greenville	South Carolina	United States	29605
121	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
122	T C Thompson Children's Hospital	Chattanooga	Tennessee	United States	37403
123	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
124	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
125	Texas Tech University Health Science Center-Amarillo	Amarillo	Texas	United States	79106
126	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
127	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
128	Medical City Dallas Hospital	Dallas	Texas	United States	75230
129	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
130	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
131	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
132	M D Anderson Cancer Center	Houston	Texas	United States	77030
133	Covenant Children's Hospital	Lubbock	Texas	United States	79410
134	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
135	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
136	Scott and White Memorial Hospital	Temple	Texas	United States	76508
137	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
138	University of Vermont College of Medicine	Burlington	Vermont	United States	05405
139	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
140	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
141	Childrens Hospital-King's Daughters	Norfolk	Virginia	United States	23507
142	Naval Medical Center - Portsmouth	Portsmouth	Virginia	United States	23708-2197
143	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
144	Carilion Clinic Children's Hospital	Roanoke	Virginia	United States	24014
145	Seattle Children's Hospital	Seattle	Washington	United States	98105
146	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
147	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington	United States	98405
148	Madigan Army Medical Center	Tacoma	Washington	United States	98431
149	West Virginia University Charleston	Charleston	West Virginia	United States	25304
150	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
151	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
152	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
153	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
154	Royal Brisbane and Women's Hospital	Herston	Queensland	Australia	4029
155	Women's and Children's Hospital-Adelaide	North Adelaide	South Australia	Australia	5006
156	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6008
157	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
158	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
159	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
160	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
161	Janeway Child Health Centre	Saint John's	Newfoundland and Labrador	Canada	A1B 3V6
162	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
163	Chedoke Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8S 4L8
164	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 5P9
165	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
166	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
167	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
168	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
169	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
170	Centre Hospitalier Universitaire de Quebec	Quebec		Canada	G1V 4G2
171	Schneider Children's Medical Center of Israel	Petah Tikua		Israel	49202
172	Starship Children's Hospital	Grafton	Auckland	New Zealand	1145
173	Christchurch Hospital	Christchurch		New Zealand	8011
174	San Jorge Children's Hospital	San Juan		Puerto Rico	00912
175	Swiss Pediatric Oncology Group - Geneva	Geneva		Switzerland	1205

Sponsors and Collaborators

Children's Oncology Group
National Cancer Institute (NCI)

Investigators

Principal Investigator: Debra Friedman, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Children's Oncology Group

ClinicalTrials.gov Identifier:

NCT00025259

Other Study ID Numbers:

AHOD0031
NCI-2011-02069
CDR0000068943
COG-AHOD0031
AHOD0031
AHOD0031
U10CA098543

First Posted:

Jan 27, 2003

Last Update Posted:

Apr 12, 2017

Last Verified:

May 1, 2016

Additional relevant MeSH terms:

Dexamethasone acetate

Liposomal doxorubicin

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	Arm I (Patients Off-therapy Before Callback-Induction Only)	Arm II (RER With CR [ABVE-PC, IFRT])	Arm III (RER With CR [ABVE-PC])	Arm IV (RER With Less Than CR [ABVE-PC, IFRT])	Arm V (RER With PD)	Arm VI (SER [DECA, ABVE-PC, IFRT])	Arm VII (SER [ABVE-PC, IFRT])
Arm/Group Description	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	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	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	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	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	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	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
Period Title: Overall Study
STARTED	52	381	382	571	42	153	153
COMPLETED	7	292	301	457	6	101	102
NOT COMPLETED	45	89	81	114	36	52	51

Baseline Characteristics

Arm/Group Title	Arm I (Patients Off-therapy Before Callback-Induction Only)	Arm II (RER With CR [ABVE-PC, IFRT])	Arm III (RER With CR [ABVE-PC])	Arm IV (RER With Less Than CR [ABVE-PC, IFRT])	Arm V (RER With PD)	Arm VI (SER [DECA, ABVE-PC, IFRT])	Arm VII (SER [ABVE-PC, IFRT])	Total
Arm/Group Description	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	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	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	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	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	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	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	Total of all reporting groups
Overall Participants	52	381	382	571	42	153	153	1734
Age (Count of Participants)
<=18 years	46 88.5%	363 95.3%	369 96.6%	540 94.6%	40 95.2%	143 93.5%	148 96.7%	1649 95.1%
Between 18 and 65 years	6 11.5%	18 4.7%	13 3.4%	31 5.4%	2 4.8%	10 6.5%	5 3.3%	85 4.9%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	16	14	14	15	15	15	15	15
Sex: Female, Male (Count of Participants)
Female	21 40.4%	177 46.5%	155 40.6%	288 50.4%	16 38.1%	81 52.9%	77 50.3%	815 47%
Male	31 59.6%	204 53.5%	227 59.4%	283 49.6%	26 61.9%	72 47.1%	76 49.7%	919 53%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 13.5%	71 18.6%	67 17.5%	74 13%	4 9.5%	22 14.4%	14 9.2%	259 14.9%
Not Hispanic or Latino	44 84.6%	293 76.9%	306 80.1%	487 85.3%	34 81%	127 83%	134 87.6%	1425 82.2%
Unknown or Not Reported	1 1.9%	17 4.5%	9 2.4%	10 1.8%	4 9.5%	4 2.6%	5 3.3%	50 2.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 0.3%	2 0.4%	0 0%	0 0%	1 0.7%	4 0.2%
Asian	1 1.9%	15 3.9%	12 3.1%	11 1.9%	1 2.4%	4 2.6%	6 3.9%	50 2.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	2 0.5%	2 0.4%	1 2.4%	1 0.7%	0 0%	6 0.3%
Black or African American	5 9.6%	45 11.8%	43 11.3%	67 11.7%	6 14.3%	14 9.2%	14 9.2%	194 11.2%
White	41 78.8%	290 76.1%	297 77.7%	444 77.8%	30 71.4%	122 79.7%	124 81%	1348 77.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	5 9.6%	31 8.1%	27 7.1%	45 7.9%	4 9.5%	12 7.8%	8 5.2%	132 7.6%
Region of Enrollment (participants) [Number]
New Zealand	1 1.9%	0 0%	0 0%	3 0.5%	0 0%	0 0%	0 0%	4 0.2%
Canada	8 15.4%	30 7.9%	45 11.8%	51 8.9%	1 2.4%	20 13.1%	20 13.1%	175 10.1%
United States	41 78.8%	333 87.4%	312 81.7%	491 86%	39 92.9%	125 81.7%	128 83.7%	1469 84.7%
Israel	0 0%	3 0.8%	1 0.3%	1 0.2%	0 0%	1 0.7%	0 0%	6 0.3%
Australia	0 0%	8 2.1%	13 3.4%	12 2.1%	0 0%	3 2%	4 2.6%	40 2.3%
Switzerland	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%	0 0%	1 0.1%
Kuwait	1 1.9%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.1%
France	0 0%	1 0.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 0.1%
Netherlands	0 0%	2 0.5%	9 2.4%	7 1.2%	1 2.4%	3 2%	0 0%	22 1.3%
Puerto Rico	1 1.9%	4 1%	2 0.5%	4 0.7%	0 0%	1 0.7%	1 0.7%	13 0.7%
Bermuda	0 0%	0 0%	0 0%	1 0.2%	0 0%	0 0%	0 0%	1 0.1%
French Polynesia	0 0%	0 0%	0 0%	0 0%	1 2.4%	0 0%	0 0%	1 0.1%

Outcome Measures

1. Primary Outcome

Title	Event-free Survival
Description	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.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
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).

Arm/Group Title	Arm I (Patients Off-therapy Before Callback-Induction Only)	Arm II (RER With CR [ABVE-PC, IFRT])	Arm III (RER With CR [ABVE-PC])	Arm IV (RER With Less Than CR [ABVE-PC, IFRT])	Arm V (RER With PD)	Arm VI (SER [DECA, ABVE-PC, IFRT])	Arm VII (SER [ABVE-PC, IFRT])
Arm/Group Description	All patients-off therapy before callback-Induction only	RER with Complete Response - IFRT (Standard Arm)	RER with Complete Response - no IFRT (Reduced Therapy Arm)	RER with less than Complete Response - IFRT	RER with Progressive Disease - Off Therapy	SER - randomized to DECAX2 + ABVE-PCX2 + IFRT	SER - randomized to ABVE-PCX2 + IFRT
Measure Participants	38	380	382	571	36	153	152
Number (95% Confidence Interval) [Probability of survival]	0.89	0.87	0.84	0.87	0.70	0.79	0.74

2. Secondary Outcome

Title	Disease Response Assessed by Modified RECIST Criteria
Description	Number of participants with complete response and very good partial response at the end of protocol therapy.
Time Frame	Protocol therapy: the overall duration of which is: (n=1527) an average of 137.1 days, median 133.0 days, interquartile range: 101.0, 164.0 days.

Outcome Measure Data

Analysis Population Description
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).

Arm/Group Title	Arm I (Patients Off-therapy Before Callback-Induction Only)	Arm II (RER With CR [ABVE-PC, IFRT])	Arm III (RER With CR [ABVE-PC])	Arm IV (RER With Less Than CR [ABVE-PC, IFRT])	Arm V (RER With PD)	Arm VI (SER [DECA, ABVE-PC, IFRT])	Arm VII (SER [ABVE-PC, IFRT])
Arm/Group Description	All patients-off therapy before callback-Induction only	RER with Complete Response - IFRT (Standard Arm)	RER with Complete Response - no IFRT ( Reduced Therapy Arm)	RER with less than Complete Response - IFRT	RER with Progressive Disease - Off Therapy	SER - randomized to DECAX2 + ABVE-PCX2 + IFRT	SER - randomized to ABVE-PCX2 + IFRT
Measure Participants	38	380	382	571	36	153	152
Number [Number of participants]	5 9.6%	370 97.1%	380 99.5%	538 94.2%	29 69%	105 68.6%	100 65.4%

3. Secondary Outcome

Title	Grade 3 or 4 Non-hematologic Toxicity
Description	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.
Time Frame	Protocol therapy: the overall duration of which is: (n=1684) an average of 137.3 days, median 133.0 days, interquartile range: 101.0, 164.0 days.

Outcome Measure Data

Analysis Population Description
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).

Arm/Group Title	Arm I (Patients Off-therapy Before Callback-Induction Only)	Arm II (RER With CR [ABVE-PC, IFRT])	Arm III (RER With CR [ABVE-PC])	Arm IV (RER With Less Than CR [ABVE-PC, IFRT])	Arm V (RER With PD)	Arm VI (SER [DECA, ABVE-PC, IFRT])	Arm VII (SER [ABVE-PC, IFRT])
Arm/Group Description	All patients-off therapy before callback-Induction only	RER with Complete Response - IFRT (Standard Arm)	RER with Complete Response - no IFRT ( Reduced Therapy Arm)	RER with less than Complete Response - IFRT	RER with Progressive Disease - Off Therapy	SER - randomized to DECAX2 + ABVE-PCX2 + IFRT	SER - randomized to ABVE-PCX2 + IFRT
Measure Participants	38	380	382	571	36	153	152
Number [Number of participants]	10 19.2%	153 40.2%	130 34%	216 37.8%	11 26.2%	62 40.5%	45 29.4%

4. Secondary Outcome

Title	Overall Survival
Description	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.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description
Arm V (RER with PD), has been excluded as there were no deaths observed by the Time Frame of 5 years. 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).

Arm/Group Title	Arm I (Patients Off-therapy Before Callback-Induction Only)	Arm II (RER With CR [ABVE-PC, IFRT])	Arm III (RER With CR [ABVE-PC])	Arm IV (RER With Less Than CR [ABVE-PC, IFRT])	Arm VI (SER [DECA, ABVE-PC, IFRT])	Arm VII (SER [ABVE-PC, IFRT])
Arm/Group Description	All patients-off therapy before callback-Induction only	RER with Complete Response - IFRT (Standard Arm)	RER with Complete Response - no IFRT ( Reduced Therapy Arm)	RER with less than Complete Response - IFRT	SER - randomized to DECAX2 + ABVE-PCX2 + IFRT	SER - randomized to ABVE-PCX2 + IFRT
Measure Participants	38	380	382	571	153	152
Number (95% Confidence Interval) [Probability of survival]	0.93	0.98	0.98	0.98	0.96	0.93

Adverse Events

	Arm I (Patients Off-therapy Before Callback-Induction Only)		Arm II (RER With CR [ABVE-PC, IFRT])		Arm III (RER With CR [ABVE-PC])		Arm IV (RER With Less Than CR [ABVE-PC, IFRT])		Arm V (RER With PD)		Arm VI (SER [DECA, ABVE-PC, IFRT])		Arm VII (SER [ABVE-PC, IFRT])
Time Frame
Adverse Event Reporting Description	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).

Arm/Group Title	Arm I (Patients Off-therapy Before Callback-Induction Only)		Arm II (RER With CR [ABVE-PC, IFRT])		Arm III (RER With CR [ABVE-PC])		Arm IV (RER With Less Than CR [ABVE-PC, IFRT])		Arm V (RER With PD)		Arm VI (SER [DECA, ABVE-PC, IFRT])		Arm VII (SER [ABVE-PC, IFRT])
Arm/Group Description	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		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		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		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		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		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		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
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Patients Off-therapy Before Callback-Induction Only)		Arm II (RER With CR [ABVE-PC, IFRT])		Arm III (RER With CR [ABVE-PC])		Arm IV (RER With Less Than CR [ABVE-PC, IFRT])		Arm V (RER With PD)		Arm VI (SER [DECA, ABVE-PC, IFRT])		Arm VII (SER [ABVE-PC, IFRT])
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/38 (2.6%)		2/380 (0.5%)		1/382 (0.3%)		5/571 (0.9%)		1/36 (2.8%)		2/153 (1.3%)		1/152 (0.7%)
Blood and lymphatic system disorders
Anemia	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Blood and lymphatic system disorders - Other, specify	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Febrile neutropenia	0/38 (0%)	0	1/380 (0.3%)	1	1/382 (0.3%)	1	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Gastrointestinal disorders
Diarrhea	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Nausea	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Vomiting	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Immune system disorders
Anaphylaxis	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	2/571 (0.4%)	2	1/36 (2.8%)	1	0/153 (0%)	0	1/152 (0.7%)	1
Investigations
Blood antidiuretic hormone abnormal	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Lymphocyte count decreased	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Neutrophil count decreased	0/38 (0%)	0	2/380 (0.5%)	2	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Platelet count decreased	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
White blood cell decreased	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	2/571 (0.4%)	2	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Nervous system disorders
Peripheral motor neuropathy	1/38 (2.6%)	1	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Hypoxia	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Patients Off-therapy Before Callback-Induction Only)		Arm II (RER With CR [ABVE-PC, IFRT])		Arm III (RER With CR [ABVE-PC])		Arm IV (RER With Less Than CR [ABVE-PC, IFRT])		Arm V (RER With PD)		Arm VI (SER [DECA, ABVE-PC, IFRT])		Arm VII (SER [ABVE-PC, IFRT])
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/38 (60.5%)		341/380 (89.7%)		334/382 (87.4%)		497/571 (87%)		26/36 (72.2%)		135/153 (88.2%)		133/152 (87.5%)
Blood and lymphatic system disorders
Anemia	4/38 (10.5%)	4	196/380 (51.6%)	196	162/382 (42.4%)	162	245/571 (42.9%)	245	12/36 (33.3%)	12	85/153 (55.6%)	85	63/152 (41.4%)	63
Blood and lymphatic system disorders - Other, specify	1/38 (2.6%)	1	50/380 (13.2%)	50	35/382 (9.2%)	35	57/571 (10%)	57	0/36 (0%)	0	31/153 (20.3%)	31	20/152 (13.2%)	20
Disseminated intravascular coagulation	1/38 (2.6%)	1	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Febrile neutropenia	5/38 (13.2%)	5	111/380 (29.2%)	111	99/382 (25.9%)	99	128/571 (22.4%)	128	3/36 (8.3%)	3	45/153 (29.4%)	45	31/152 (20.4%)	31
Cardiac disorders
Cardiac disorders - Other, specify	2/38 (5.3%)	2	1/380 (0.3%)	1	2/382 (0.5%)	2	1/571 (0.2%)	1	0/36 (0%)	0	3/153 (2%)	3	0/152 (0%)	0
Left ventricular systolic dysfunction	1/38 (2.6%)	1	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Sinus tachycardia	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	2/571 (0.4%)	2	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Supraventricular tachycardia	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Ear and labyrinth disorders
Hearing impaired	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Endocrine disorders
Endocrine disorders - Other, specify	0/38 (0%)	0	0/380 (0%)	0	1/382 (0.3%)	1	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Eye disorders
Blurred vision	0/38 (0%)	0	0/380 (0%)	0	1/382 (0.3%)	1	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Eye disorders - Other, specify	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/38 (5.3%)	2	4/380 (1.1%)	4	6/382 (1.6%)	6	12/571 (2.1%)	12	0/36 (0%)	0	1/153 (0.7%)	1	1/152 (0.7%)	1
Anal fistula	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Ascites	1/38 (2.6%)	1	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Colitis	1/38 (2.6%)	1	3/380 (0.8%)	3	0/382 (0%)	0	5/571 (0.9%)	5	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Constipation	0/38 (0%)	0	4/380 (1.1%)	4	4/382 (1%)	4	2/571 (0.4%)	2	1/36 (2.8%)	1	1/153 (0.7%)	1	0/152 (0%)	0
Diarrhea	1/38 (2.6%)	1	2/380 (0.5%)	2	2/382 (0.5%)	2	9/571 (1.6%)	9	0/36 (0%)	0	3/153 (2%)	3	0/152 (0%)	0
Dyspepsia	0/38 (0%)	0	2/380 (0.5%)	2	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Dysphagia	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Esophagitis	0/38 (0%)	0	2/380 (0.5%)	2	2/382 (0.5%)	2	2/571 (0.4%)	2	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Gastric hemorrhage	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Gastrointestinal disorders - Other, specify	1/38 (2.6%)	1	1/380 (0.3%)	1	0/382 (0%)	0	2/571 (0.4%)	2	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Ileus	0/38 (0%)	0	3/380 (0.8%)	3	2/382 (0.5%)	2	3/571 (0.5%)	3	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Lower gastrointestinal hemorrhage	1/38 (2.6%)	1	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Mucositis oral	0/38 (0%)	0	20/380 (5.3%)	20	9/382 (2.4%)	9	25/571 (4.4%)	25	1/36 (2.8%)	1	10/153 (6.5%)	10	2/152 (1.3%)	2
Nausea	1/38 (2.6%)	1	6/380 (1.6%)	6	5/382 (1.3%)	5	21/571 (3.7%)	21	0/36 (0%)	0	6/153 (3.9%)	6	2/152 (1.3%)	2
Pancreatitis	0/38 (0%)	0	2/380 (0.5%)	2	1/382 (0.3%)	1	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Rectal hemorrhage	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	1/152 (0.7%)	1
Rectal pain	0/38 (0%)	0	2/380 (0.5%)	2	0/382 (0%)	0	2/571 (0.4%)	2	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Typhlitis	3/38 (7.9%)	3	4/380 (1.1%)	4	3/382 (0.8%)	3	7/571 (1.2%)	7	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Vomiting	1/38 (2.6%)	1	6/380 (1.6%)	6	9/382 (2.4%)	9	19/571 (3.3%)	19	0/36 (0%)	0	9/153 (5.9%)	9	3/152 (2%)	3
General disorders
Chills	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Fatigue	1/38 (2.6%)	1	1/380 (0.3%)	1	1/382 (0.3%)	1	3/571 (0.5%)	3	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Fever	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	5/571 (0.9%)	5	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
General disorders and administration site conditions - Other, specify	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Non-cardiac chest pain	0/38 (0%)	0	1/380 (0.3%)	1	1/382 (0.3%)	1	1/571 (0.2%)	1	0/36 (0%)	0	2/153 (1.3%)	2	0/152 (0%)	0
Pain	0/38 (0%)	0	4/380 (1.1%)	4	4/382 (1%)	4	13/571 (2.3%)	13	0/36 (0%)	0	2/153 (1.3%)	2	0/152 (0%)	0
Immune system disorders
Anaphylaxis	1/38 (2.6%)	1	14/380 (3.7%)	14	8/382 (2.1%)	8	20/571 (3.5%)	20	1/36 (2.8%)	1	4/153 (2.6%)	4	6/152 (3.9%)	6
Immune system disorders - Other, specify	0/38 (0%)	0	1/380 (0.3%)	1	2/382 (0.5%)	2	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Infections and infestations
Catheter related infection	3/38 (7.9%)	3	14/380 (3.7%)	14	13/382 (3.4%)	13	17/571 (3%)	17	1/36 (2.8%)	1	3/153 (2%)	3	4/152 (2.6%)	4
Infections and infestations - Other, specify	4/38 (10.5%)	4	71/380 (18.7%)	71	61/382 (16%)	61	79/571 (13.8%)	79	6/36 (16.7%)	6	26/153 (17%)	26	16/152 (10.5%)	16
Wound infection	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	2/153 (1.3%)	2	0/152 (0%)	0
Investigations
Activated partial thromboplastin time prolonged	1/38 (2.6%)	1	2/380 (0.5%)	2	0/382 (0%)	0	2/571 (0.4%)	2	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Alanine aminotransferase increased	0/38 (0%)	0	1/380 (0.3%)	1	1/382 (0.3%)	1	5/571 (0.9%)	5	0/36 (0%)	0	1/153 (0.7%)	1	2/152 (1.3%)	2
Aspartate aminotransferase increased	0/38 (0%)	0	0/380 (0%)	0	1/382 (0.3%)	1	2/571 (0.4%)	2	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Blood antidiuretic hormone abnormal	0/38 (0%)	0	0/380 (0%)	0	1/382 (0.3%)	1	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Blood bilirubin increased	1/38 (2.6%)	1	0/380 (0%)	0	0/382 (0%)	0	3/571 (0.5%)	3	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Carbon monoxide diffusing capacity decreased	2/38 (5.3%)	2	11/380 (2.9%)	11	3/382 (0.8%)	3	11/571 (1.9%)	11	0/36 (0%)	0	3/153 (2%)	3	0/152 (0%)	0
Cardiac troponin I increased	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Fibrinogen decreased	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Forced expiratory volume decreased	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
INR increased	0/38 (0%)	0	3/380 (0.8%)	3	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Investigations - Other, specify	0/38 (0%)	0	1/380 (0.3%)	1	1/382 (0.3%)	1	0/571 (0%)	0	0/36 (0%)	0	2/153 (1.3%)	2	0/152 (0%)	0
Lipase increased	0/38 (0%)	0	0/380 (0%)	0	1/382 (0.3%)	1	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Lymphocyte count decreased	2/38 (5.3%)	2	14/380 (3.7%)	14	19/382 (5%)	19	53/571 (9.3%)	53	1/36 (2.8%)	1	24/153 (15.7%)	24	17/152 (11.2%)	17
Neutrophil count decreased	17/38 (44.7%)	17	319/380 (83.9%)	319	307/382 (80.4%)	307	449/571 (78.6%)	449	20/36 (55.6%)	20	126/153 (82.4%)	126	116/152 (76.3%)	116
Platelet count decreased	3/38 (7.9%)	3	152/380 (40%)	152	119/382 (31.2%)	119	167/571 (29.2%)	167	5/36 (13.9%)	5	98/153 (64.1%)	98	55/152 (36.2%)	55
Serum amylase increased	1/38 (2.6%)	1	1/380 (0.3%)	1	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Weight loss	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
White blood cell decreased	5/38 (13.2%)	5	71/380 (18.7%)	71	69/382 (18.1%)	69	126/571 (22.1%)	126	1/36 (2.8%)	1	50/153 (32.7%)	50	31/152 (20.4%)	31
Metabolism and nutrition disorders
Acidosis	1/38 (2.6%)	1	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	1/152 (0.7%)	1
Anorexia	1/38 (2.6%)	1	4/380 (1.1%)	4	1/382 (0.3%)	1	0/571 (0%)	0	0/36 (0%)	0	3/153 (2%)	3	0/152 (0%)	0
Dehydration	0/38 (0%)	0	3/380 (0.8%)	3	10/382 (2.6%)	10	9/571 (1.6%)	9	0/36 (0%)	0	2/153 (1.3%)	2	2/152 (1.3%)	2
Hypercalcemia	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Hyperglycemia	1/38 (2.6%)	1	7/380 (1.8%)	7	5/382 (1.3%)	5	4/571 (0.7%)	4	1/36 (2.8%)	1	8/153 (5.2%)	8	1/152 (0.7%)	1
Hyperkalemia	0/38 (0%)	0	2/380 (0.5%)	2	0/382 (0%)	0	3/571 (0.5%)	3	0/36 (0%)	0	3/153 (2%)	3	1/152 (0.7%)	1
Hyperuricemia	0/38 (0%)	0	0/380 (0%)	0	1/382 (0.3%)	1	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Hypoalbuminemia	1/38 (2.6%)	1	2/380 (0.5%)	2	2/382 (0.5%)	2	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Hypocalcemia	1/38 (2.6%)	1	4/380 (1.1%)	4	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Hypoglycemia	0/38 (0%)	0	1/380 (0.3%)	1	1/382 (0.3%)	1	3/571 (0.5%)	3	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Hypokalemia	2/38 (5.3%)	2	12/380 (3.2%)	12	7/382 (1.8%)	7	17/571 (3%)	17	0/36 (0%)	0	5/153 (3.3%)	5	1/152 (0.7%)	1
Hypomagnesemia	0/38 (0%)	0	0/380 (0%)	0	1/382 (0.3%)	1	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Hyponatremia	1/38 (2.6%)	1	7/380 (1.8%)	7	4/382 (1%)	4	9/571 (1.6%)	9	0/36 (0%)	0	2/153 (1.3%)	2	1/152 (0.7%)	1
Hypophosphatemia	0/38 (0%)	0	2/380 (0.5%)	2	2/382 (0.5%)	2	5/571 (0.9%)	5	0/36 (0%)	0	3/153 (2%)	3	0/152 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	2/571 (0.4%)	2	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Arthritis	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Bone pain	0/38 (0%)	0	0/380 (0%)	0	3/382 (0.8%)	3	7/571 (1.2%)	7	0/36 (0%)	0	0/153 (0%)	0	4/152 (2.6%)	4
Generalized muscle weakness	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Musculoskeletal and connective tissue disorder - Other, specify	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	2/571 (0.4%)	2	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Myalgia	0/38 (0%)	0	0/380 (0%)	0	2/382 (0.5%)	2	4/571 (0.7%)	4	0/36 (0%)	0	1/153 (0.7%)	1	1/152 (0.7%)	1
Myositis	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Nervous system disorders
Dizziness	0/38 (0%)	0	1/380 (0.3%)	1	2/382 (0.5%)	2	2/571 (0.4%)	2	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Headache	0/38 (0%)	0	4/380 (1.1%)	4	3/382 (0.8%)	3	6/571 (1.1%)	6	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Nervous system disorders - Other, specify	0/38 (0%)	0	0/380 (0%)	0	1/382 (0.3%)	1	2/571 (0.4%)	2	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Neuralgia	0/38 (0%)	0	7/380 (1.8%)	7	3/382 (0.8%)	3	6/571 (1.1%)	6	0/36 (0%)	0	1/153 (0.7%)	1	1/152 (0.7%)	1
Peripheral motor neuropathy	0/38 (0%)	0	1/380 (0.3%)	1	3/382 (0.8%)	3	8/571 (1.4%)	8	1/36 (2.8%)	1	0/153 (0%)	0	0/152 (0%)	0
Peripheral sensory neuropathy	0/38 (0%)	0	1/380 (0.3%)	1	5/382 (1.3%)	5	4/571 (0.7%)	4	1/36 (2.8%)	1	1/153 (0.7%)	1	0/152 (0%)	0
Pyramidal tract syndrome	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Seizure	0/38 (0%)	0	0/380 (0%)	0	2/382 (0.5%)	2	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Syncope	0/38 (0%)	0	5/380 (1.3%)	5	5/382 (1.3%)	5	7/571 (1.2%)	7	0/36 (0%)	0	2/153 (1.3%)	2	1/152 (0.7%)	1
Vasovagal reaction	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Psychiatric disorders
Anxiety	0/38 (0%)	0	0/380 (0%)	0	1/382 (0.3%)	1	3/571 (0.5%)	3	0/36 (0%)	0	1/153 (0.7%)	1	2/152 (1.3%)	2
Depression	0/38 (0%)	0	1/380 (0.3%)	1	2/382 (0.5%)	2	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Insomnia	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	2/571 (0.4%)	2	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Personality change	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	3/571 (0.5%)	3	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Psychosis	0/38 (0%)	0	1/380 (0.3%)	1	1/382 (0.3%)	1	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Reproductive system and breast disorders
Irregular menstruation	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Vaginal hemorrhage	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Dyspnea	1/38 (2.6%)	1	2/380 (0.5%)	2	3/382 (0.8%)	3	5/571 (0.9%)	5	0/36 (0%)	0	1/153 (0.7%)	1	1/152 (0.7%)	1
Epistaxis	0/38 (0%)	0	2/380 (0.5%)	2	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	0/152 (0%)	0
Hypoxia	0/38 (0%)	0	3/380 (0.8%)	3	2/382 (0.5%)	2	4/571 (0.7%)	4	0/36 (0%)	0	1/153 (0.7%)	1	1/152 (0.7%)	1
Pleural effusion	2/38 (5.3%)	2	2/380 (0.5%)	2	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Pleuritic pain	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Respiratory, thoracic and mediastinal disorders - Other, specify	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Skin and subcutaneous tissue disorders
Pruritus	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Rash maculo-papular	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	1/571 (0.2%)	1	0/36 (0%)	0	1/153 (0.7%)	1	0/152 (0%)	0
Skin and subcutaneous tissue disorders - Other, specify	0/38 (0%)	0	1/380 (0.3%)	1	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	0/153 (0%)	0	1/152 (0.7%)	1
Vascular disorders
Hypertension	0/38 (0%)	0	1/380 (0.3%)	1	2/382 (0.5%)	2	3/571 (0.5%)	3	0/36 (0%)	0	1/153 (0.7%)	1	1/152 (0.7%)	1
Hypotension	2/38 (5.3%)	2	11/380 (2.9%)	11	8/382 (2.1%)	8	13/571 (2.3%)	13	0/36 (0%)	0	2/153 (1.3%)	2	2/152 (1.3%)	2
Thromboembolic event	0/38 (0%)	0	7/380 (1.8%)	7	2/382 (0.5%)	2	14/571 (2.5%)	14	0/36 (0%)	0	3/153 (2%)	3	3/152 (2%)	3
Vascular disorders - Other, specify	0/38 (0%)	0	0/380 (0%)	0	0/382 (0%)	0	0/571 (0%)	0	0/36 (0%)	0	2/153 (1.3%)	2	0/152 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Must obtain prior approval.

Results Point of Contact

Name/Title	Results Reporting Coordinator
Organization	Children's Oncology Group
Phone	626-447-0064
Email	resultsreportingcoordinator@childrensoncologygroup.org

Responsible Party:

Children's Oncology Group

ClinicalTrials.gov Identifier:

NCT00025259

Other Study ID Numbers:

AHOD0031
NCI-2011-02069
CDR0000068943
COG-AHOD0031
AHOD0031
AHOD0031
U10CA098543

First Posted:

Jan 27, 2003

Last Update Posted:

Apr 12, 2017

Last Verified:

May 1, 2016

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

Study Details

Study Description

Brief Summary

Detailed Description

OBJECTIVES:

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

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Inclusion Criteria:

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Locations

Sponsors and Collaborators

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Study Results

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Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

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Results Point of Contact