Brentuximab vedotin och kombinationskemoterapi vid behandling av barn och unga vuxna med stadium IIB, stadium IIIB, IVA eller IVB Hodgkin lymfom
En randomiserad fas 3-studie av Brentuximab Vedotin (SGN-35) för nyligen diagnostiserat högrisk klassiskt Hodgkin-lymfom (cHL) hos barn och unga vuxna
This phase III trial studies brentuximab vedotin and combination chemotherapy to see how well they work compared to combination chemotherapy alone in treating children and young adults with stage IIB with bulk, stage IIIB, IVA, or IVB Hodgkin lymphoma. Combinations of biological substances in brentuximab vedotin may be able to carry cancer-killing substances directly to Hodgkin lymphoma cells. Chemotherapy drugs, such as doxorubicin hydrochloride, bleomycin sulfate, vincristine sulfate, etoposide, prednisone, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known if combination chemotherapy is more effective with or without brentuximab vedotin in treating children with high-risk Hodgkin lymphoma.
Studieöversikt
Status
Betingelser
Intervention / Behandling
- Övrig: Laboratory Biomarker Analysis
- Övrig: Quality-of-Life Assessment
- Läkemedel: Cyclophosphamide
- Läkemedel: Doxorubicin Hydrochloride
- Läkemedel: Prednisone
- Läkemedel: Vincristine Sulfate
- Övrig: Questionnaire Administration
- Läkemedel: Brentuximab Vedotin
- Läkemedel: Etoposide
- Övrig: Pharmacological Study
- Biologisk: Bleomycin Sulfate
- Läkemedel: Methylprednisolone
Detaljerad beskrivning
PRIMARY OBJECTIVE:
I. To assess the event free survival (EFS) of a novel regimen incorporating brentuximab vedotin (Bv; Adcetris) in the chemotherapy backbone of doxorubicin hydrochloride (doxorubicin) (Adriamycin), vincristine sulfate (vincristine), etoposide, prednisone and cyclophosphamide (Bv-AVEPC) in newly diagnosed high-risk classical Hodgkin lymphoma (cHL) compared to those treated with Adriamycin, bleomycin sulfate, vincristine sulfate, etoposide, prednisone, and cyclophosphamide (ABVE-PC).
SECONDARY OBJECTIVES:
I. To determine whether children/young adults with high-risk cHL treated with Bv-AVEPC have a higher rate of early response (determined by fludeoxyglucose F 18 [FDG]-positron emission tomography [PET]) and a reduction in protocol directed radiation therapy (RT) compared to those treated with ABVE-PC.
II. To compare the rate of neuropathy (>= grade 3) among patients treated on the Bv-AVEPC (experimental arm) to patients treated on the ABVE-PC (standard arm).
EXPLORATORY OBJECTIVES:
I. To validate and compare the Childhood Hodgkin International Prognostic Score (CHIPS) to conventional Ann Arbor stage (stages II B with bulk, III B, IV A or B) in predicting outcome in high-risk childhood cHL.
II. To determine the incidence of preferentially expressed antigen in melanoma (PRAME) and testis-specific antigens in Epstein-Barr virus (EBV)- cHL tumors and the incidence of EBV antigens (Epstein-Barr nuclear antigen 1 [EBNA1], Epstein-Barr virus latent membrane protein 1 [LMP1], large multifunctional peptidase 2 [LMP2]) in EBV+ cHL tumors, with the goal of developing strategies to integrate cellular therapy into treatment for newly diagnosed high-risk cHL. (Biology) III. To incorporate qualitative visual FDG-PET into response-directed treatment algorithms and explore quantitative FDG-PET and computed tomography (CT) definitions of tumor burden and response for incorporation into next generation pediatric cHL risk-stratification schemes, exploring the extension of these algorithms to young adults. (Imaging) IV. To evaluate the reduction in normal tissue irradiation associated with the current treatment approach compared to the volume of historic involved field radiation therapy (IFRT) fields. (Radiation Therapy) V. To evaluate EFS and patterns of relapse following protocol-specified RT utilization and treatment volumes. (Radiation Therapy) VI. To characterize the extent of chemotherapy induced peripheral neuropathy (CIPN), as reported by patients and parent proxies, through serial administration of the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTX). (Patient Reported Outcomes [PRO] of Peripheral Neuropathy and Health-Related Quality of Life) VII. To describe the Health-Related Quality of Life (HRQL) consequences of peripheral neuropathy over time by correlating total neuropathy scale scores with the individual items with the Child Health Ratings Inventories (CHRIs)-Global scale (e.g., physical health, pain, emotional functioning). (PRO of Peripheral Neuropathy and Health-Related Quality of Life) VIII. To perform a cross validation of the FACT-GOG-NTX with the Total Neuropathy Score-Pediatric Vincristine (TNS-PV) to determine the performance of both measures with the use of brentuximab vedotin in a limited institutional approach in children and adolescents with cHL. (PRO of Peripheral Neuropathy and Health-Related Quality of Life) IX. To assess the resource use and cost implications of Bv in combination with chemotherapy and radiotherapy (RT) for newly diagnosed high-risk cHL in children and young adults. (Economic) X. To estimate the risk of relapse among rapidly responding lesions (RRL) subjects that have at least one lesion that is Deauville 3 at PET 2. (Follow-up of Deauville score 3 lesions on FDG-PET imaging [confirmed by central imaging review]) XI. To characterize the pharmacokinetics of brentuximab vedotin in children < 13 years of age.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I (ABVE-PC): Patients receive doxorubicin hydrochloride intravenously (IV) over on days 1-2, bleomycin sulfate IV or subcutaneously (SC) on days 1 and 8, vincristine sulfate IV on days 1 and 8, etoposide IV on days 1-3, prednisone orally (PO) twice daily (BID) or methylprednisolone IV on days 1-7, and cyclophosphamide IV on days 1 and 2.
ARM II (Bv-AVEPC): Patients receive brentuximab vedotin IV on day 1. Patients also receive doxorubicin hydrochloride, etoposide, prednisone or methylprednisolone, and cyclophosphamide as in Arm I and vincristine sulfate IV on day 8.
In both arms, treatment repeats every 21 days for 5 cycles in the absence of disease progression or unacceptable toxicity. Granulocyte simulating factor (GCSF) or equivalent is given on both arms.
After completion of study treatment, patients are followed up at 3, 6, 9, 12, 18, 24, 30, 36, and 48 months.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 3
Kontakter och platser
Studieorter
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Alabama
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Birmingham, Alabama, Förenta staterna, 35233
- Children's Hospital of Alabama
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Mobile, Alabama, Förenta staterna, 36604
- USA Health Strada Patient Care Center
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Alaska
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Anchorage, Alaska, Förenta staterna, 99508
- Providence Alaska Medical Center
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Arizona
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Mesa, Arizona, Förenta staterna, 85202
- Banner Children's at Desert
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Phoenix, Arizona, Förenta staterna, 85016
- Phoenix Childrens Hospital
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Tucson, Arizona, Förenta staterna, 85719
- Banner University Medical Center - Tucson
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Arkansas
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Little Rock, Arkansas, Förenta staterna, 72202-3591
- Arkansas Children's Hospital
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California
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Downey, California, Förenta staterna, 90242
- Kaiser Permanente Downey Medical Center
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Duarte, California, Förenta staterna, 91010
- City of Hope Comprehensive Cancer Center
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Loma Linda, California, Förenta staterna, 92354
- Loma Linda University Medical Center
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Long Beach, California, Förenta staterna, 90806
- Miller Children's and Women's Hospital Long Beach
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Los Angeles, California, Förenta staterna, 90048
- Cedars-Sinai Medical Center
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Los Angeles, California, Förenta staterna, 90027
- Children's Hospital Los Angeles
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Madera, California, Förenta staterna, 93636
- Valley Children's Hospital
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Oakland, California, Förenta staterna, 94611
- Kaiser Permanente-Oakland
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Orange, California, Förenta staterna, 92868
- Children's Hospital of Orange County
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Sacramento, California, Förenta staterna, 95816
- Sutter Medical Center Sacramento
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Sacramento, California, Förenta staterna, 95817
- University of California Davis Comprehensive Cancer Center
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San Diego, California, Förenta staterna, 92123
- Rady Children's Hospital - San Diego
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San Diego, California, Förenta staterna, 92134
- Naval Medical Center -San Diego
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Santa Barbara, California, Förenta staterna, 93102
- Santa Barbara Cottage Hospital
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Torrance, California, Förenta staterna, 90502
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
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Colorado
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Aurora, Colorado, Förenta staterna, 80045
- Children's Hospital Colorado
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Denver, Colorado, Förenta staterna, 80218
- Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
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Connecticut
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Hartford, Connecticut, Förenta staterna, 06106
- Connecticut Children's Medical Center
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New Haven, Connecticut, Förenta staterna, 06520
- Yale University
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Delaware
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Wilmington, Delaware, Förenta staterna, 19803
- Alfred I duPont Hospital for Children
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District of Columbia
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Washington D.C., District of Columbia, Förenta staterna, 20010
- Children's National Medical Center
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Washington D.C., District of Columbia, Förenta staterna, 20007
- MedStar Georgetown University Hospital
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Florida
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Fort Lauderdale, Florida, Förenta staterna, 33316
- Broward Health Medical Center
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Fort Myers, Florida, Förenta staterna, 33908
- Golisano Children's Hospital of Southwest Florida
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Gainesville, Florida, Förenta staterna, 32610
- UF Health Cancer Institute - Gainesville
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Hollywood, Florida, Förenta staterna, 33021
- Memorial Regional Hospital/Joe DiMaggio Children's Hospital
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Jacksonville, Florida, Förenta staterna, 32207
- Nemours Children's Clinic-Jacksonville
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Miami, Florida, Förenta staterna, 33155
- Nicklaus Children's Hospital
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Miami, Florida, Förenta staterna, 33136
- University of Miami Miller School of Medicine-Sylvester Cancer Center
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Miami, Florida, Förenta staterna, 33176
- Miami Cancer Institute
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Orlando, Florida, Förenta staterna, 32827
- Nemours Children's Hospital
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Orlando, Florida, Förenta staterna, 32803
- AdventHealth Orlando
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Orlando, Florida, Förenta staterna, 32806
- Arnold Palmer Hospital for Children
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Pensacola, Florida, Förenta staterna, 32504
- Nemours Children's Clinic - Pensacola
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St. Petersburg, Florida, Förenta staterna, 33701
- Johns Hopkins All Children's Hospital
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Tampa, Florida, Förenta staterna, 33606
- Tampa General Hospital
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Tampa, Florida, Förenta staterna, 33607
- Saint Joseph's Hospital/Children's Hospital-Tampa
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West Palm Beach, Florida, Förenta staterna, 33407
- Saint Mary's Medical Center
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Georgia
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Atlanta, Georgia, Förenta staterna, 30329
- Children's Healthcare of Atlanta - Arthur M Blank Hospital
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Augusta, Georgia, Förenta staterna, 30912
- Augusta University Medical Center
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Savannah, Georgia, Förenta staterna, 31404
- Memorial Health University Medical Center
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Hawaii
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Honolulu, Hawaii, Förenta staterna, 96826
- Kapiolani Medical Center for Women and Children
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Idaho
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Boise, Idaho, Förenta staterna, 83712
- Saint Luke's Cancer Institute - Boise
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Illinois
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Chicago, Illinois, Förenta staterna, 60637
- University of Chicago Comprehensive Cancer Center
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Chicago, Illinois, Förenta staterna, 60612
- University of Illinois
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Chicago, Illinois, Förenta staterna, 60611
- Lurie Children's Hospital-Chicago
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Maywood, Illinois, Förenta staterna, 60153
- Loyola University Medical Center
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Oak Lawn, Illinois, Förenta staterna, 60453
- Advocate Children's Hospital-Oak Lawn
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Park Ridge, Illinois, Förenta staterna, 60068
- Advocate Children's Hospital-Park Ridge
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Peoria, Illinois, Förenta staterna, 61637
- OSF Children's Hospital of Illinois
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Springfield, Illinois, Förenta staterna, 62702
- Southern Illinois University School of Medicine
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Indiana
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Indianapolis, Indiana, Förenta staterna, 46202
- Riley Hospital for Children
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Indianapolis, Indiana, Förenta staterna, 46260
- Ascension Saint Vincent Indianapolis Hospital
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Iowa
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Des Moines, Iowa, Förenta staterna, 50309
- Blank Children's Hospital
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Iowa City, Iowa, Förenta staterna, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Kentucky
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Lexington, Kentucky, Förenta staterna, 40536
- University of Kentucky/Markey Cancer Center
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Louisville, Kentucky, Förenta staterna, 40202
- Norton Children's Hospital
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Louisiana
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New Orleans, Louisiana, Förenta staterna, 70121
- Ochsner Medical Center Jefferson
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New Orleans, Louisiana, Förenta staterna, 70118
- Children's Hospital New Orleans
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Maine
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Bangor, Maine, Förenta staterna, 04401
- Eastern Maine Medical Center
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Maryland
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Baltimore, Maryland, Förenta staterna, 21287
- Johns Hopkins University/Sidney Kimmel Cancer Center
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Baltimore, Maryland, Förenta staterna, 21215
- Sinai Hospital of Baltimore
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Baltimore, Maryland, Förenta staterna, 21201
- University of Maryland/Greenebaum Cancer Center
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Bethesda, Maryland, Förenta staterna, 20889-5600
- Walter Reed National Military Medical Center
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Massachusetts
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Boston, Massachusetts, Förenta staterna, 02111
- Tufts Children's Hospital
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Springfield, Massachusetts, Förenta staterna, 01199
- Baystate Medical Center
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Worcester, Massachusetts, Förenta staterna, 01655
- UMass Memorial Medical Center - University Campus
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Michigan
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Ann Arbor, Michigan, Förenta staterna, 48109
- C S Mott Children's Hospital
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Detroit, Michigan, Förenta staterna, 48201
- Wayne State University/Karmanos Cancer Institute
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Detroit, Michigan, Förenta staterna, 48236
- Henry Ford Health Saint John Hospital
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East Lansing, Michigan, Förenta staterna, 48823
- Michigan State University
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Flint, Michigan, Förenta staterna, 48503
- Hurley Medical Center
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Grand Rapids, Michigan, Förenta staterna, 49503
- Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
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Kalamazoo, Michigan, Förenta staterna, 49007
- Bronson Methodist Hospital
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Royal Oak, Michigan, Förenta staterna, 48073
- Corewell Health Children's
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Minnesota
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Minneapolis, Minnesota, Förenta staterna, 55404
- Children's Hospitals and Clinics of Minnesota - Minneapolis
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Minneapolis, Minnesota, Förenta staterna, 55455
- University of Minnesota/Masonic Cancer Center
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Rochester, Minnesota, Förenta staterna, 55905
- Mayo Clinic in Rochester
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Mississippi
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Jackson, Mississippi, Förenta staterna, 39216
- University of Mississippi Medical Center
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Missouri
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Columbia, Missouri, Förenta staterna, 65212
- University of Missouri Children's Hospital
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Kansas City, Missouri, Förenta staterna, 64108
- Children's Mercy Hospitals and Clinics
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St Louis, Missouri, Förenta staterna, 63110
- Washington University School of Medicine
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St Louis, Missouri, Förenta staterna, 63141
- Mercy Hospital Saint Louis
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St Louis, Missouri, Förenta staterna, 63104
- Cardinal Glennon Children's Medical Center
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Nebraska
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Omaha, Nebraska, Förenta staterna, 68198
- University of Nebraska Medical Center
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Omaha, Nebraska, Förenta staterna, 68114
- Children's Hospital and Medical Center of Omaha
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Nevada
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Las Vegas, Nevada, Förenta staterna, 89144
- Summerlin Hospital Medical Center
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Las Vegas, Nevada, Förenta staterna, 89109
- Sunrise Hospital and Medical Center
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Las Vegas, Nevada, Förenta staterna, 89135
- Alliance for Childhood Diseases/Cure 4 the Kids Foundation
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Las Vegas, Nevada, Förenta staterna, 89102
- University Medical Center of Southern Nevada
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New Hampshire
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Lebanon, New Hampshire, Förenta staterna, 03756
- Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
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New Jersey
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Hackensack, New Jersey, Förenta staterna, 07601
- Hackensack University Medical Center
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Morristown, New Jersey, Förenta staterna, 07960
- Morristown Medical Center
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New Brunswick, New Jersey, Förenta staterna, 08901
- Saint Peter's University Hospital
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New Brunswick, New Jersey, Förenta staterna, 08903
- Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
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Newark, New Jersey, Förenta staterna, 07112
- Newark Beth Israel Medical Center
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Paterson, New Jersey, Förenta staterna, 07503
- Saint Joseph's Regional Medical Center
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New Mexico
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Albuquerque, New Mexico, Förenta staterna, 87106
- University of New Mexico Cancer Center
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New York
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Albany, New York, Förenta staterna, 12208
- Albany Medical Center
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Buffalo, New York, Förenta staterna, 14263
- Roswell Park Cancer Institute
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Mineola, New York, Förenta staterna, 11501
- NYU Langone Hospital - Long Island
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New Hyde Park, New York, Förenta staterna, 11040
- The Steven and Alexandra Cohen Children's Medical Center of New York
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New York, New York, Förenta staterna, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Förenta staterna, 10029
- Mount Sinai Hospital
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New York, New York, Förenta staterna, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
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New York, New York, Förenta staterna, 10065
- NYP/Weill Cornell Medical Center
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New York, New York, Förenta staterna, 10016
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
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Rochester, New York, Förenta staterna, 14642
- University of Rochester
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Stony Brook, New York, Förenta staterna, 11794
- Stony Brook University Medical Center
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Syracuse, New York, Förenta staterna, 13210
- State University of New York Upstate Medical University
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The Bronx, New York, Förenta staterna, 10467
- Montefiore Medical Center - Moses Campus
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North Carolina
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Asheville, North Carolina, Förenta staterna, 28801
- Mission Hospital
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Chapel Hill, North Carolina, Förenta staterna, 27599
- UNC Lineberger Comprehensive Cancer Center
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Charlotte, North Carolina, Förenta staterna, 28203
- Carolinas Medical Center/Levine Cancer Institute
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Charlotte, North Carolina, Förenta staterna, 28204
- Novant Health Presbyterian Medical Center
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Durham, North Carolina, Förenta staterna, 27710
- Duke University Medical Center
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Greenville, North Carolina, Förenta staterna, 27834
- East Carolina University
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Winston-Salem, North Carolina, Förenta staterna, 27157
- Wake Forest University Health Sciences
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North Dakota
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Fargo, North Dakota, Förenta staterna, 58122
- Sanford Broadway Medical Center
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Ohio
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Akron, Ohio, Förenta staterna, 44308
- Children's Hospital Medical Center of Akron
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Cincinnati, Ohio, Förenta staterna, 45229
- Cincinnati Children's Hospital Medical Center
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Cleveland, Ohio, Förenta staterna, 44195
- Cleveland Clinic Foundation
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Cleveland, Ohio, Förenta staterna, 44106
- Rainbow Babies and Childrens Hospital
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Columbus, Ohio, Förenta staterna, 43205
- Nationwide Children's Hospital
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Dayton, Ohio, Förenta staterna, 45404
- Dayton Children's Hospital
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Toledo, Ohio, Förenta staterna, 43606
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
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Oklahoma
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Oklahoma City, Oklahoma, Förenta staterna, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Portland, Oregon, Förenta staterna, 97239
- Oregon Health and Science University
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Portland, Oregon, Förenta staterna, 97227
- Legacy Emanuel Children's Hospital
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Pennsylvania
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Allentown, Pennsylvania, Förenta staterna, 18103
- Lehigh Valley Hospital-Cedar Crest
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Bethlehem, Pennsylvania, Förenta staterna, 18017
- Lehigh Valley Hospital - Muhlenberg
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Danville, Pennsylvania, Förenta staterna, 17822
- Geisinger Medical Center
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Hershey, Pennsylvania, Förenta staterna, 17033
- Penn State Children's Hospital
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Philadelphia, Pennsylvania, Förenta staterna, 19104
- Children's Hospital of Philadelphia
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Philadelphia, Pennsylvania, Förenta staterna, 19134
- Saint Christopher's Hospital for Children
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Pittsburgh, Pennsylvania, Förenta staterna, 15224
- Children's Hospital of Pittsburgh of UPMC
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Rhode Island
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Providence, Rhode Island, Förenta staterna, 02903
- Rhode Island Hospital
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South Carolina
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Charleston, South Carolina, Förenta staterna, 29425
- Medical University of South Carolina
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Columbia, South Carolina, Förenta staterna, 29203
- Prisma Health Richland Hospital
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Greenville, South Carolina, Förenta staterna, 29605
- BI-LO Charities Children's Cancer Center
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South Dakota
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Sioux Falls, South Dakota, Förenta staterna, 57117-5134
- Sanford USD Medical Center - Sioux Falls
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Tennessee
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Chattanooga, Tennessee, Förenta staterna, 37403
- T C Thompson Children's Hospital
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Knoxville, Tennessee, Förenta staterna, 37916
- East Tennessee Childrens Hospital
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Nashville, Tennessee, Förenta staterna, 37232
- Vanderbilt University/Ingram Cancer Center
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Nashville, Tennessee, Förenta staterna, 37203
- The Children's Hospital at TriStar Centennial
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Texas
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Austin, Texas, Förenta staterna, 78723
- Dell Children's Medical Center of Central Texas
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Corpus Christi, Texas, Förenta staterna, 78411
- Driscoll Children's Hospital
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Dallas, Texas, Förenta staterna, 75390
- UT Southwestern/Simmons Cancer Center-Dallas
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Dallas, Texas, Förenta staterna, 75230
- Medical City Dallas Hospital
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El Paso, Texas, Förenta staterna, 79905
- El Paso Children's Hospital
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Fort Worth, Texas, Förenta staterna, 76104
- Cook Children's Medical Center
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Houston, Texas, Förenta staterna, 77030
- UT MD Anderson Cancer Center
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Houston, Texas, Förenta staterna, 77030
- Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
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Lubbock, Texas, Förenta staterna, 79410
- Covenant Children's Hospital
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Lubbock, Texas, Förenta staterna, 79415
- UMC Cancer Center / UMC Health System
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San Antonio, Texas, Förenta staterna, 78229
- University of Texas Health Science Center at San Antonio
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San Antonio, Texas, Förenta staterna, 78207
- Children's Hospital of San Antonio
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San Antonio, Texas, Förenta staterna, 78229
- Methodist Children's Hospital of South Texas
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Temple, Texas, Förenta staterna, 76508
- Scott and White Memorial Hospital
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Utah
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Salt Lake City, Utah, Förenta staterna, 84113
- Primary Children's Hospital
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Vermont
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Burlington, Vermont, Förenta staterna, 05405
- University of Vermont and State Agricultural College
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Virginia
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Charlottesville, Virginia, Förenta staterna, 22908
- University of Virginia Cancer Center
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Falls Church, Virginia, Förenta staterna, 22042
- Inova Fairfax Hospital
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Norfolk, Virginia, Förenta staterna, 23507
- Children's Hospital of The King's Daughters
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Richmond, Virginia, Förenta staterna, 23298
- VCU Massey Comprehensive Cancer Center
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Washington
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Seattle, Washington, Förenta staterna, 98105
- Seattle Children's Hospital
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Spokane, Washington, Förenta staterna, 99204
- Providence Sacred Heart Medical Center and Children's Hospital
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Tacoma, Washington, Förenta staterna, 98405
- Mary Bridge Children's Hospital and Health Center
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Tacoma, Washington, Förenta staterna, 98431
- Madigan Army Medical Center
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West Virginia
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Charleston, West Virginia, Förenta staterna, 25304
- Vandalia Health/CAMC Institute for Academic Medicine
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Morgantown, West Virginia, Förenta staterna, 26506
- West Virginia University Healthcare
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Wisconsin
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Green Bay, Wisconsin, Förenta staterna, 54301
- Saint Vincent Hospital Cancer Center Green Bay
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Madison, Wisconsin, Förenta staterna, 53792
- University of Wisconsin Carbone Cancer Center - University Hospital
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Marshfield, Wisconsin, Förenta staterna, 54449
- Marshfield Medical Center-Marshfield
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Milwaukee, Wisconsin, Förenta staterna, 53226
- Children's Hospital of Wisconsin
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Québec, Kanada, G1V 4G2
- CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
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Alberta
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Calgary, Alberta, Kanada, T3B 6A8
- Alberta Children's Hospital
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Edmonton, Alberta, Kanada, T6G 2B7
- University of Alberta Hospital
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British Columbia
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Vancouver, British Columbia, Kanada, V6H 3V4
- British Columbia Children's Hospital
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Manitoba
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Winnipeg, Manitoba, Kanada, R3E 0V9
- CancerCare Manitoba
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Nova Scotia
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Halifax, Nova Scotia, Kanada, B3K 6R8
- IWK Health Centre
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Ontario
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Hamilton, Ontario, Kanada, L8N 3Z5
- McMaster Children's Hospital at Hamilton Health Sciences
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Kingston, Ontario, Kanada, K7L 2V7
- Kingston Health Sciences Centre
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London, Ontario, Kanada, N6A 5W9
- Children's Hospital
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Ottawa, Ontario, Kanada, K1H 8L1
- Children's Hospital of Eastern Ontario
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Toronto, Ontario, Kanada, M5G 1X8
- Hospital for Sick Children
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Quebec
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Montreal, Quebec, Kanada, H3H 1P3
- The Montreal Children's Hospital of the MUHC
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Montreal, Quebec, Kanada, H3T 1C5
- Centre Hospitalier Universitaire Sainte-Justine
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Saskatchewan
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Saskatoon, Saskatchewan, Kanada, S7N 4H4
- Saskatoon Cancer Centre
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Caguas, Puerto Rico, 00726
- HIMA San Pablo Oncologic Hospital
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San Juan, Puerto Rico, 00926
- University Pediatric Hospital
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San Juan, Puerto Rico, 00912
- San Jorge Children's Hospital
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
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Patients with newly diagnosed, pathologically confirmed cHL meeting one of the following Ann Arbor stages are eligible:
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Stage IIB with bulk
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Stage IIIB
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Stage IVA
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Stage IVB
- If study eligibility by staging is uncertain, consultation with Imaging and Radiation Oncology Core (IROC) Rhode Island (RI) may be obtained prior to study enrollment
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Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (performed within 14 days prior to enrollment):
- 2 to < 6 years: male 0.8 mg/dL, female 0.8 mg/dL
- 6 to < 10 years: male 1 mg/dL, female 1 mg/dL
- 10 to < 13 years: male 1.2 mg/dL, female 1.2 mg/dL
- 13 to < 16 years: male 1.5 mg/dL, female 1.4 mg/dL
- >= 16 years: male 1.7 mg/dL, female 1.4 mg/dL
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Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (performed within 14 days prior to enrollment)
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Serum glutamic oxaloacetic transaminase (SGOT) (aspartate transaminase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine transaminase [ALT]) < 2.5 x upper limit of normal (ULN) for age (performed within 14 days prior to enrollment)
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Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram
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Forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), unless due to large mediastinal mass from Hodgkin lymphoma (HL)
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For children who are unable to cooperate for PFTs, the criteria are: no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry reading of > 92% on room air
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All patients and/or their parents or legal guardians must sign a written informed consent
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All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
- Patients with nodular lymphocyte-predominant HL
- Patients with an immunodeficiency that existed prior to diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and children on current systemic immunosuppressive agents are not eligible
- Patients who are pregnant; (since fetal toxicities and teratogenic effects have been noted for several of the study drugs, a negative pregnancy test is required for female patients of childbearing potential)
- Lactating females who plan to breastfeed
- Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation and for 30 days after the last dose of chemotherapy
- Patients known to be positive for human immunodeficiency virus (HIV) are not eligible
- Patients who have received any previous chemotherapy or radiation therapy are not eligible
- Patients who received systemic corticosteroids within 28 days of enrollment on this protocol, except as specified, are not eligible
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Enda
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Aktiv komparator: Arm I (ABVE-PC)
Patients receive doxorubicin hydrochloride IV over on days 1-2, bleomycin sulfate IV or SC on days 1 and 8, vincristine sulfate IV on days 1 and 8, etoposide IV on days 1-3, prednisone orally PO BID or methylprednisolone IV on days 1-7, and cyclophosphamide IV on days 1 and 2. Treatment repeats every 21 days for 5 cycles in the absence of disease progression or unacceptable toxicity. |
Correlative studies Ancillary studies
Andra namn:
Given IV
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Given IV
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Given PO
Andra namn:
Given IV
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Ancillary studies Given IV
Andra namn:
Correlative studies Given IV or SC
Andra namn:
Given IV
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Experimentell: ARM II (Bv-AVEPC)
Patients receive brentuximab vedotin IV on day 1. Patients also receive doxorubicin hydrochloride, etoposide, prednisone or methylprednisolone, and cyclophosphamide as in Arm I and vincristine sulfate IV on day 8. Treatment repeats every 21 days for 5 cycles in the absence of disease progression or unacceptable toxicity. |
Correlative studies Ancillary studies
Andra namn:
Given IV
Andra namn:
Given IV
Andra namn:
Given PO
Andra namn:
Given IV
Andra namn:
Ancillary studies Given IV
Andra namn:
Given IV
Andra namn:
Correlative studies Given IV
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Event Free Survival (EFS), Where Events Include Disease Progression or Relapse, Second Malignancy, or Death
Tidsram: Up to 48 months after the last enrollment
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Primary analysis will be based 1-sided log rank test comparison of EFS curves between the 2 randomized arms per intention-to-treat principle. Progression is defined as an ≥50% increase of in the product of the perpendicular diameters of any of the involved nodes or nodal masses or focal organ lesions in sites that were persistently PET positive; or recurrent PET positive lesions (Deauville 4, 5) in sites that had previously been PET negative regardless of change of size, as was the development of new PET avid measurable lesion(s) >1.5cm in any axis, or new sites of assessable disease. Relapse is defined in patients who achieved a prior CR but subsequently has an increase of ≥50% of the PPD in prior nodal or extranodal sites in a recurrently PET positive lesion(s), or the development of new measurable lesion(s) >1.5cm in any axis, or new sites of assessable disease. Second malignancy is defined based on report of a cancer that is not considered to be classic Hodgkin Lymphoma. |
Up to 48 months after the last enrollment
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Percentages of Patients With Early Response Defined as no Slow Responding Lesions (SRL) and no Progressive Disease (PD) at Any Disease Sites Determined by Positron Emission Tomography (PET) Per Deauville Criteria Through Central Review
Tidsram: After 42 days of chemotherapy
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The percentages of patients (with available PET scan) with no SRL and no PD will be compared between the two randomized arms to see if brentuximab vedotin in the chemotherapy backbone of doxorubicin hydrochloride, vincristine sulfate, etoposide, prednisone and cyclophosphamide (Bv-AVEPC) arm has a higher rate of early response compared to doxorubicin hydrochloride, bleomycin sulfate, vincristine sulfate, etoposide, prednisone, and cyclophosphamide (ABVE-PC) arm. Two-sample Z test of proportions at 1-sided alpha level of 0.05 will be used for these comparisons. |
After 42 days of chemotherapy
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Percentages of Patients Experiencing Grade 3+ Peripheral Neuropathy Assessed by Modified Balis Scale
Tidsram: From the enrollment of the patient to the time of analysis or the last follow-up; an average of 3.6 years.
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The percentages of patients experiencing grade 3+ peripheral neuropathy assessed by the treating clinician using the modified Balis scale. The "Modified Balis scale of Pediatric Neuropathy" allows clinicians to assign a score for sensory or motor neuropathy symptoms separately. Scores range from 1 to 4 with 1 being the least symptomatic state and 4 indicating a severe debility. The percentages of patients (with a score >/=3) will be compared between the 2 arms by two-sample Z test at 1-sided alpha level of 0.05. |
From the enrollment of the patient to the time of analysis or the last follow-up; an average of 3.6 years.
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Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Childhood International Prognostic Score (CHIPS) Score
Tidsram: Baseline
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CHIPS will be computed for all patients and summarized by descriptive statistics. Will examine the association between CHIPS and early response by cross-tabulations and Chi-square tests within each arm separately, as well as logistic regression model where early response is the outcome variable and CHIPS the predictor variable combining the 2 arms with adjustment for randomized chemotherapy. |
Baseline
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Dose of Radiation Received by Normal Tissues Following Chemotherapy on Either Study Arm
Tidsram: Up to 48 months
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Descriptive statistics will be used to summarize RT doses received by normal tissues on this study. Two-sample t-test will be used to compare the doses received on this study to those on prior studies. |
Up to 48 months
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Efficacy of Involved Site Radiotherapy (ISRT) by Analyzing the Event-free Survival of Patients Treated With Response-adapted ISRT and by Evaluating Patterns of Relapse Following ISRT
Tidsram: Up to 3 years
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EFS for patients on each arm as well as those receiving ISRT or those with slow early response (SER) on each arm will be estimated. One-sample log rank test will be used to compare the observed EFS to the assumed baseline of 82% at 3 years to see if the observed EFS is significantly lower than the projection in these subsets. |
Up to 3 years
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Risk of Relapse Among RRL Subjects That Have at Least One Lesion That is Deauville 3 at PET 2
Tidsram: Up to 48 months after the last enrollment
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The risk of relapse for cases that are RRL, but have Deauville 3 lesions, will be compared to those that are classified as complete metabolic response at PET2 with solely Deauville 1 or 2 lesions with K-sample test. |
Up to 48 months after the last enrollment
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Pharmacokinetic (PK) Analyses
Tidsram: Pre-dose and end of infusion on day 1, days 2, 3, 8, and 15 of cycle 4 and pre-dose on day 1 and day 22 of cycle 5 (each cycle = 21 days)
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PK concentration time profile will be evaluated. |
Pre-dose and end of infusion on day 1, days 2, 3, 8, and 15 of cycle 4 and pre-dose on day 1 and day 22 of cycle 5 (each cycle = 21 days)
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Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: Sharon M Castellino, Children's Oncology Group
Publikationer och användbara länkar
Allmänna publikationer
- Castellino SM, Pei Q, Parsons SK, Hodgson D, McCarten K, Horton T, Cho S, Wu Y, Punnett A, Dave H, Henderson TO, Hoppe BS, Charpentier AM, Keller FG, Kelly KM. Brentuximab Vedotin with Chemotherapy in Pediatric High-Risk Hodgkin's Lymphoma. N Engl J Med. 2022 Nov 3;387(18):1649-1660. doi: 10.1056/NEJMoa2206660.
- Castellino SM, Giulino-Roth L, Harker-Murray P, Kahn JM, Forlenza C, Cho S, Hoppe B, Parsons SK, Kelly KM; COG Hodgkin Lymphoma Committee. Children's Oncology Group's 2023 blueprint for research: Hodgkin lymphoma. Pediatr Blood Cancer. 2023 Sep;70 Suppl 6(Suppl 6):e30580. doi: 10.1002/pbc.30580. Epub 2023 Jul 28.
- Tie X, Shin M, Lee C, Perlman SB, Huemann Z, Weisman AJ, Castellino SM, Kelly KM, McCarten KM, Alazraki AL, Hu J, Cho SY, Bradshaw TJ. Automatic Quantification of Serial PET/CT Images for Pediatric Hodgkin Lymphoma Using a Longitudinally Aware Segmentation Network. Radiol Artif Intell. 2025 May;7(3):e240229. doi: 10.1148/ryai.240229.
- Pabari R, McCarten K, Flerlage J, Lai H, Mauz-Korholz C, Dieckmann K, Palese M, Kaste S, Castellino SM, Kelly KM, Stoevesandt D, Kurch L. Hodgkin lymphoma involving the extra-axial CNS: an AHOD1331, PHL-C1, and PHL-C2 report from the COG and EuroNet-PHL. Blood Adv. 2024 Sep 24;8(18):4856-4865. doi: 10.1182/bloodadvances.2023012346.
- Williams AM, Rodday AM, Pei Q, Henderson TO, Keller FG, Punnett A, Kelly KM, Castellino SM, Parsons SK. Longitudinal Health-Related Quality of Life Among Patients With High-Risk Pediatric Hodgkin Lymphoma Treated on the Children's Oncology Group AHOD 1331 Study. J Clin Oncol. 2024 Oct;42(28):3330-3338. doi: 10.1200/JCO.24.00038. Epub 2024 Jul 26.
- Parsons SK, Rodday AM, Pei Q, Keller FG, Wu Y, Henderson TO, Cella D, Kelly KM, Castellino SM. Performance of the FACT-GOG-Ntx to assess chemotherapy-induced peripheral neuropathy (CIPN) in pediatric high risk Hodgkin lymphoma: report from the Children's Oncology Group AHOD 1331 study. J Patient Rep Outcomes. 2023 Nov 10;7(1):113. doi: 10.1186/s41687-023-00653-0.
- Hoppe BS, McCarten KM, Pei Q, Kessel S, Alazraki A, Mhlanga JC, Lai HA, Eutsler E, Hodgson DC, Roberts KB, Charpentier AM, Keller FG, Voss SD, Wu Y, Cho SY, Kelly KM, Castellino SM. Importance of Central Imaging Review in a Pediatric Hodgkin Lymphoma Trial Using Positron Emission Tomography Response Adapted Radiation Therapy. Int J Radiat Oncol Biol Phys. 2023 Aug 1;116(5):1025-1030. doi: 10.1016/j.ijrobp.2023.02.020. Epub 2023 Mar 2.
- Williams AM, Rodday AM, Renfro LA, Wu Y, Henderson TO, Keller FG, Punnett A, Hodgson D, Kelly KM, Castellino SM, Parsons SK. Group-based trajectories of health-related quality of life among pediatric patients with high-risk Hodgkin lymphoma. J Natl Cancer Inst. 2025 Oct 1;117(10):2112-2119. doi: 10.1093/jnci/djaf197.
- Toner K, Renfro LA, Dave H, Pezzella G, Pei Q, Giulino-Roth L, Horton T, Keller FG, Kelly KM, Castellino SM, Bollard CM. Tumor-specific immune responses and biomarkers in pediatric patients with high-risk Hodgkin lymphoma. Blood Adv. 2026 Jan 13;10(1):183-191. doi: 10.1182/bloodadvances.2025016797.
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Beräknad)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Beräknad)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Peptider
- Aminosyror, peptider och proteiner
- Oligopeptider
- Proteiner
- Organiska kemikalier
- Heterocykliska föreningar
- Heterocykliska föreningar, 2-ring
- Heterocykliska föreningar, smältring
- Kolväten
- Kolväten, cykliska
- Kolhydrater
- Alkaloider
- Podofyllotoxin
- Tetrahydronaftaler
- Naftalar
- Polycykliska aromatiska kolväten
- Kolväten, aromatisk
- Polycykliska föreningar
- Glukosider
- Glykosider
- Förenad
- Antikroppar, monoklonal, humaniserad
- Antikroppar, monoklonal
- Antikroppar
- Immunglobuliner
- Immunoproteiner
- Blodproteiner
- Serumglobuliner
- Globuliner
- Graviditet
- Graviditet
- Steroider
- Fusion-ringföreningar
- Fosforamidsen
- Kväve senapsföreningar
- Senapsföreningar
- Kolväten, halogenerad
- Fosforamider
- Organofosforföreningar
- Graviditet
- Gravidioder
- Vinca alkaloider
- Secologanin tryptaminalkaloider
- Indolalkaloider
- Indolizidiner
- Indoliziner
- Anthracykliner
- Naftakener
- Aminoglykosider
- Glykokonjugat
- Daunorubicin
- Glykopeptider
- Prednisolon
- Brentuximab Vedotin
- Prednison
- Cyklofosfamid
- Etoposid
- Doxorubicin
- Vincristine
- Metylprednisolon
- Bleomycin
- deltacortene
- prednyliden
- exifon
- Medrol veriderm
Andra studie-ID-nummer
- NCI-2014-01223
- U10CA180886 (U.S.S. NIH-anslag/kontrakt)
- NCI-2014-01223 (Registeridentifierare: CTRP (Clinical Trial Reporting Program))
- s15-00950
- AHOD1331 (Annan identifierare: CTEP)
- AHOD1331 (Annan identifierare: Children's Oncology Group)
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