Brentuximab Vedotin and Combination Chemotherapy in Treating Children and Young Adults With Stage IIB, Stage IIIB, IVA, or IVB Hodgkin Lymphoma

Classic Hodgkin Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02166463
• Other study ID #: NCI-2014-01223
• Secondary ID: NCI-2014-01223s1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 19, 2015
• Est. completion date: September 22, 2024

Study information

• Verified date: November 2023
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 600
• Est. completion date: September 22, 2024
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 22 Years

Eligibility

Inclusion Criteria:

• 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
• 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

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

Related Conditions & MeSH terms

• 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
• Hodgkin Disease
• Lymphoma

Intervention

Biological:
• Bleomycin Sulfate
Given IV or SC

Drug:
• Brentuximab Vedotin
Given IV
• Cyclophosphamide
Given IV
• Doxorubicin Hydrochloride
Given IV
• Etoposide
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Methylprednisolone
Given IV

Other:
• Pharmacological Study
Correlative studies

Drug:
• Prednisone
Given PO

Other:
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Drug:
• Vincristine Sulfate
Given IV

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	Kingston Health Sciences Centre	Kingston	Ontario
Canada	Children's Hospital	London	Ontario
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec
Canada	The Montreal Children's Hospital of the MUHC	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)	Quebec
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Puerto Rico	HIMA San Pablo Oncologic Hospital	Caguas
Puerto Rico	San Jorge Children's Hospital	San Juan
Puerto Rico	University Pediatric Hospital	San Juan
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Mission Hospital	Asheville	North Carolina
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Augusta University Medical Center	Augusta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Walter Reed National Military Medical Center	Bethesda	Maryland
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Children's Hospital of Alabama	Birmingham	Alabama
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Tufts Children's Hospital	Boston	Massachusetts
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont and State Agricultural College	Burlington	Vermont
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Charleston Division	Charleston	West Virginia
United States	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	University of Virginia Cancer Center	Charlottesville	Virginia
United States	T C Thompson Children's Hospital	Chattanooga	Tennessee
United States	Lurie Children's Hospital-Chicago	Chicago	Illinois
United States	University of Chicago Comprehensive Cancer Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Columbia Regional	Columbia	Missouri
United States	Prisma Health Richland Hospital	Columbia	South Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Medical City Dallas Hospital	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Geisinger Medical Center	Danville	Pennsylvania
United States	Dayton Children's Hospital	Dayton	Ohio
United States	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado
United States	Blank Children's Hospital	Des Moines	Iowa
United States	Ascension Saint John Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Kaiser Permanente Downey Medical Center	Downey	California
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Michigan State University Clinical Center	East Lansing	Michigan
United States	El Paso Children's Hospital	El Paso	Texas
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Broadway Medical Center	Fargo	North Dakota
United States	Hurley Medical Center	Flint	Michigan
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin
United States	BI-LO Charities Children's Cancer Center	Greenville	South Carolina
United States	East Carolina University	Greenville	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Children's Hospital	Hershey	Pennsylvania
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Ascension Saint Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	Riley Hospital for Children	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Summerlin Hospital Medical Center	Las Vegas	Nevada
United States	Sunrise Hospital and Medical Center	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Miller Children's and Women's Hospital Long Beach	Long Beach	California
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Norton Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	UMC Cancer Center / UMC Health System	Lubbock	Texas
United States	Valley Children's Hospital	Madera	California
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	Banner Children's at Desert	Mesa	Arizona
United States	Miami Cancer Institute	Miami	Florida
United States	Nicklaus Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	NYU Winthrop Hospital	Mineola	New York
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	USA Health Strada Patient Care Center	Mobile	Alabama
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Morristown Medical Center	Morristown	New Jersey
United States	The Children's Hospital at TriStar Centennial	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Saint Peter's University Hospital	New Brunswick	New Jersey
United States	Yale University	New Haven	Connecticut
United States	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York
United States	Children's Hospital New Orleans	New Orleans	Louisiana
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	NYP/Weill Cornell Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois
United States	Kaiser Permanente-Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Arnold Palmer Hospital for Children	Orlando	Florida
United States	Nemours Children's Hospital	Orlando	Florida
United States	Advocate Children's Hospital-Park Ridge	Park Ridge	Illinois
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Nemours Children's Clinic - Pensacola	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Legacy Emanuel Children's Hospital	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Beaumont Children's Hospital-Royal Oak	Royal Oak	Michigan
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Children's Hospital of San Antonio	San Antonio	Texas
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Naval Medical Center -San Diego	San Diego	California
United States	Rady Children's Hospital - San Diego	San Diego	California
United States	Santa Barbara Cottage Hospital	Santa Barbara	California
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Seattle Children's Hospital	Seattle	Washington
United States	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Baystate Medical Center	Springfield	Massachusetts
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	Tampa	Florida
United States	Tampa General Hospital	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital	Toledo	Ohio
United States	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	Children's National Medical Center	Washington	District of Columbia
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Saint Mary's Hospital	West Palm Beach	Florida
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Childhood International Prognostic Score (CHIPS) Score	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
Other	Dose of Radiation Received by Normal Tissues Following Chemotherapy on Either Study Arm	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
Other	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	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
Other	Risk of Relapse Among RRL Subjects That Have at Least One Lesion That is Deauville 3 at PET 2	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
Other	Pharmacokinetic (PK) Analyses	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)
Primary	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.	Up to 48 months after the last enrollment
Secondary	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.	After 42 days of chemotherapy
Secondary	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.	From the enrollment of the patient to the time of analysis or the last follow-up; an average of 3.6 years.