Ann Arbor Stage IIB Hodgkin LymphomaPhase 3NCT02166463
Brentuximab Vedotin and Combination Chemotherapy in Treating Children and Young Adults With Stage IIB, Stage IIIB, IVA, or IVB Hodgkin Lymphoma
A Phase 3 study testing Bleomycin Sulfate, Brentuximab Vedotin and Cyclophosphamide in people with Ann Arbor Stage IIB Hodgkin Lymphoma and Ann Arbor Stage IIIB Hodgkin Lymphoma, run by National Cancer Institute (NCI) at 199 sites in 3 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 2 to 22 years
- Conditions the study is for
- Ann Arbor Stage IIB Hodgkin Lymphoma, Ann Arbor Stage IIIB Hodgkin Lymphoma, Ann Arbor Stage IVA Hodgkin Lymphoma
- What is being tested?
- Bleomycin Sulfate, Brentuximab Vedotin and Cyclophosphamide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 199 sitesin 3 countries
- Study dates
- 19 Mar 2015to 3 Oct 2026
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with newly diagnosed, pathologically confirmed cHL meeting one of the following Ann Arbor stages are eligible:
- Stage IIB with bulk
- Stage IIIB
- Stage IVA
- 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
Show all 19Show fewer
- 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
- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age (performed within 14 days prior to enrollment)
- 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)
- Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by radionuclide angiogram
- 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)
- 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
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Who cannot join
- 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
Trial locations and contacts
199 sites in 3 countries.
199 sites in 3 countries
United States182 sites
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308
Albany Medical Center
Albany, New York, 12208
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103
Providence Alaska Medical Center
Anchorage, Alaska, 99508
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109
Mission Hospital
Asheville, North Carolina, 28801
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329
Augusta University Medical Center
Augusta, Georgia, 30912
Children's Hospital Colorado
Aurora, Colorado, 80045
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
Eastern Maine Medical Center
Bangor, Maine, 04401
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600
Lehigh Valley Hospital - Muhlenberg
Bethlehem, Pennsylvania, 18017
Children's Hospital of Alabama
Birmingham, Alabama, 35233
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712
Tufts Children's Hospital
Boston, Massachusetts, 02111
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Vermont and State Agricultural College
Burlington, Vermont, 05405
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Medical University of South Carolina
Charleston, South Carolina, 29425
Vandalia Health/CAMC Institute for Academic Medicine
Charleston, West Virginia, 25304
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
T C Thompson Children's Hospital
Chattanooga, Tennessee, 37403
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611
University of Illinois
Chicago, Illinois, 60612
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Rainbow Babies and Childrens Hospital
Cleveland, Ohio, 44106
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Missouri Children's Hospital
Columbia, Missouri, 65212
Prisma Health Richland Hospital
Columbia, South Carolina, 29203
Nationwide Children's Hospital
Columbus, Ohio, 43205
Driscoll Children's Hospital
Corpus Christi, Texas, 78411
Medical City Dallas Hospital
Dallas, Texas, 75230
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390
Geisinger Medical Center
Danville, Pennsylvania, 17822
Dayton Children's Hospital
Dayton, Ohio, 45404
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218
Blank Children's Hospital
Des Moines, Iowa, 50309
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201
Henry Ford Health Saint John Hospital
Detroit, Michigan, 48236
Kaiser Permanente Downey Medical Center
Downey, California, 90242
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
Duke University Medical Center
Durham, North Carolina, 27710
Michigan State University
East Lansing, Michigan, 48823
El Paso Children's Hospital
El Paso, Texas, 79905
Inova Fairfax Hospital
Falls Church, Virginia, 22042
Sanford Broadway Medical Center
Fargo, North Dakota, 58122
Hurley Medical Center
Flint, Michigan, 48503
Broward Health Medical Center
Fort Lauderdale, Florida, 33316
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908
Cook Children's Medical Center
Fort Worth, Texas, 76104
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301
East Carolina University
Greenville, North Carolina, 27834
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Connecticut Children's Medical Center
Hartford, Connecticut, 06106
Penn State Children's Hospital
Hershey, Pennsylvania, 17033
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
UT MD Anderson Cancer Center
Houston, Texas, 77030
Riley Hospital for Children
Indianapolis, Indiana, 46202
Ascension Saint Vincent Indianapolis Hospital
Indianapolis, Indiana, 46260
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108
East Tennessee Childrens Hospital
Knoxville, Tennessee, 37916
University Medical Center of Southern Nevada
Las Vegas, Nevada, 89102
Sunrise Hospital and Medical Center
Las Vegas, Nevada, 89109
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591
Loma Linda University Medical Center
Loma Linda, California, 92354
Miller Children's and Women's Hospital Long Beach
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Norton Children's Hospital
Louisville, Kentucky, 40202
Covenant Children's Hospital
Lubbock, Texas, 79410
UMC Cancer Center / UMC Health System
Lubbock, Texas, 79415
Valley Children's Hospital
Madera, California, 93636
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449
Loyola University Medical Center
Maywood, Illinois, 60153
Banner Children's at Desert
Mesa, Arizona, 85202
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Nicklaus Children's Hospital
Miami, Florida, 33155
Miami Cancer Institute
Miami, Florida, 33176
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
NYU Langone Hospital - Long Island
Mineola, New York, 11501
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, 55404
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455
USA Health Strada Patient Care Center
Mobile, Alabama, 36604
West Virginia University Healthcare
Morgantown, West Virginia, 26506
Morristown Medical Center
Morristown, New Jersey, 07960
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232
Saint Peter's University Hospital
New Brunswick, New Jersey, 08901
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903
Yale University
New Haven, Connecticut, 06520
The Steven and Alexandra Cohen Children's Medical Center of New York
New Hyde Park, New York, 11040
Children's Hospital New Orleans
New Orleans, Louisiana, 70118
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016
Mount Sinai Hospital
New York, New York, 10029
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
NYP/Weill Cornell Medical Center
New York, New York, 10065
Newark Beth Israel Medical Center
Newark, New Jersey, 07112
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507
Advocate Children's Hospital-Oak Lawn
Oak Lawn, Illinois, 60453
Kaiser Permanente-Oakland
Oakland, California, 94611
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114
University of Nebraska Medical Center
Omaha, Nebraska, 68198
Children's Hospital of Orange County
Orange, California, 92868
AdventHealth Orlando
Orlando, Florida, 32803
Arnold Palmer Hospital for Children
Orlando, Florida, 32806
Nemours Children's Hospital
Orlando, Florida, 32827
Advocate Children's Hospital-Park Ridge
Park Ridge, Illinois, 60068
Saint Joseph's Regional Medical Center
Paterson, New Jersey, 07503
Nemours Children's Clinic - Pensacola
Pensacola, Florida, 32504
OSF Children's Hospital of Illinois
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134
Phoenix Childrens Hospital
Phoenix, Arizona, 85016
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Oregon Health and Science University
Portland, Oregon, 97239
Rhode Island Hospital
Providence, Rhode Island, 02903
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
University of Rochester
Rochester, New York, 14642
Corewell Health Children's
Royal Oak, Michigan, 48073
Sutter Medical Center Sacramento
Sacramento, California, 95816
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Primary Children's Hospital
Salt Lake City, Utah, 84113
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Methodist Children's Hospital of South Texas
San Antonio, Texas, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
Rady Children's Hospital - San Diego
San Diego, California, 92123
Naval Medical Center -San Diego
San Diego, California, 92134
Santa Barbara Cottage Hospital
Santa Barbara, California, 93102
Memorial Health University Medical Center
Savannah, Georgia, 31404
Seattle Children's Hospital
Seattle, Washington, 98105
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204
Southern Illinois University School of Medicine
Springfield, Illinois, 62702
Baystate Medical Center
Springfield, Massachusetts, 01199
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104
Washington University School of Medicine
St Louis, Missouri, 63110
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701
Stony Brook University Medical Center
Stony Brook, New York, 11794
State University of New York Upstate Medical University
Syracuse, New York, 13210
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405
Madigan Army Medical Center
Tacoma, Washington, 98431
Tampa General Hospital
Tampa, Florida, 33606
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607
Scott and White Memorial Hospital
Temple, Texas, 76508
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467
ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
Toledo, Ohio, 43606
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502
Banner University Medical Center - Tucson
Tucson, Arizona, 85719
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Saint Mary's Medical Center
West Palm Beach, Florida, 33407
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
UMass Memorial Medical Center - University Campus
Worcester, Massachusetts, 01655
Canada14 sites
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5
Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
Children's Hospital
London, Ontario, N6A 5W9
The Montreal Children's Hospital of the MUHC
Montreal, Quebec, H3H 1P3
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, S7N 4H4
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9
Puerto Rico3 sites
HIMA San Pablo Oncologic Hospital
Caguas, 00726
San Jorge Children's Hospital
San Juan, 00912
University Pediatric Hospital
San Juan, 00926
About this study
Official title: A Randomized Phase 3 Study of Brentuximab Vedotin (SGN-35) for Newly Diagnosed High-Risk Classical Hodgkin Lymphoma (cHL) in Children and Young Adults
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- Conditions
- Ann Arbor Stage IIB Hodgkin Lymphoma, Ann Arbor Stage IIIB Hodgkin Lymphoma, Ann Arbor Stage IVA Hodgkin Lymphoma, Ann Arbor Stage IVB Hodgkin Lymphoma, Childhood Hodgkin Lymphoma, Classic Hodgkin Lymphoma
- Being tested
- Bleomycin Sulfate, Brentuximab Vedotin, Cyclophosphamide, Doxorubicin Hydrochloride, Etoposide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bleomycin SulfateBiological
Also called Blanoxan, BleMomycine, Blenoxane, Bleo-cell
Given IV or SC
Brentuximab VedotinDrug
Also called ADC SGN-35, Adcetris, Anti-CD30 Antibody-Drug Conjugate SGN-35, Anti-CD30 Monoclonal Antibody-MMAE SGN-35
Given IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518
Given IV
Also called 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
Given IV
EtoposideDrug
Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar
Given IV
Laboratory Biomarker AnalysisOther
Correlative studies
Also called Adlone, Caberdelta M, DepMedalone, Depo Moderin
Given IV
Correlative studies
PrednisoneDrug
Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I (ABVE-PC) | Active comparator | 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. Receives: Biological: Bleomycin Sulfate; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Etoposide; Other: Laboratory Biomarker Analysis; Drug: Methylprednisolone; Other: Pharmacological Study; Drug: Prednisone; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Vincristine Sulfate |
| ARM II (Bv-AVEPC) | Experimental | 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. Receives: Drug: Brentuximab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin Hydrochloride; Drug: Etoposide; Other: Laboratory Biomarker Analysis; Drug: Methylprednisolone; Other: Pharmacological Study; Drug: Prednisone; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Vincristine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event Free Survival (EFS), Where Events Include Disease Progression or Relapse, Second Malignancy, or Death
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.
Measured: Up to 48 months after the last enrollment
Secondary outcomes (2)
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
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.
Measured: After 42 days of chemotherapy
Percentages of Patients Experiencing Grade 3+ Peripheral Neuropathy Assessed by Modified Balis Scale
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.
Measured: From the enrollment of the patient to the time of analysis or the last follow-up; an average of 3.6 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2014 (estimated)
- Study start19 Mar 2015
- Primary completion31 Dec 2021
- Study completion3 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Ann Arbor Stage IIB Hodgkin LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 600 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sharon M Castellino, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02166463
- Sponsor's protocol ID
- NCI-2014-01223
- Other IDs
- NCI-2014-01223, s15-00950, AHOD1331, AHOD1331, U10CA180886
- Status last verified
- Jun 2026
- First submitted
- 16 Jun 2014
- Last updated
- 1 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 40990939Williams 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.
PubMed 40700618Tie 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.
PubMed 39969278Pabari 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.
PubMed 39058968Williams 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.
PubMed 39058966Parsons 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.
PubMed 37947987Castellino 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.
PubMed 37505794Hoppe 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.
PubMed 36868525Castellino 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.
PubMed 36322844