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

Stage IV Childhood Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00025259
• Other study ID #: AHOD0031
• Secondary ID: NCI-2011-02069CD
• Status: Completed
• Phase: Phase 3
• First received: October 11, 2001
• Last updated: May 27, 2016
• Start date: September 2002

Study information

• Verified date: May 2016
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Description:

OBJECTIVES:

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

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

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

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

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

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

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

OUTLINE: This is a randomized, multicenter study.

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

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

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

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

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

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

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

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

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

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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1734
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

Inclusion Criteria:

• Patients with newly diagnosed, pathologically confirmed Hodgkin disease (all histologies) are eligible for this protocol if they meet the following clinical stage guidelines:

• All Stage IB regardless of bulk disease

• All Stage IIB regardless of bulk disease

• Stage IA only with bulk disease

• Stage IIA only with bulk disease

• All Stage IAE, IIAE regardless of bulk disease

• All Stage IIIA, IIIAE, IIIAS, IIIAE+S regardless of bulk disease

• All Stage IVA, IVAE regardless of bulk disease

• May not be staged by laparotomy alone

• Surgically staged patients must also have presurgical staging

• Bilirubin no greater than 1.5 times normal

• SGOT or SGPT less than 2.5 times normal

• Creatinine no greater than 1.5 times normal

• Creatinine clearance greater than 40 mL/min

• Radioisotope glomerular filtration rate greater than 70 mL/min

• Shortening fraction at least 27% by echocardiogram

• Ejection fraction at least 50% by MUGA

• No pathologic prolongation of QTc interval on 12-lead electrocardiogram

• FEV_1/FVC greater than 60% by pulmonary function test

• Pulse oximetry greater than 94%

• No evidence of dyspnea at rest

• No exercise intolerance

• Adequate venous access

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No prior chemotherapy

• At least 1 month since prior corticosteroids except prednisone for respiratory distress

• No prior radiotherapy

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Childhood Lymphocyte-Depleted Classical Hodgkin Lymphoma
• Childhood Mixed Cellularity Classical Hodgkin Lymphoma
• Childhood Nodular Lymphocyte Predominant Hodgkin Lymphoma
• Childhood Nodular Sclerosis Classical Hodgkin Lymphoma
• Hodgkin Disease
• Lymphoma
• Stage I Childhood Hodgkin Lymphoma
• Stage II Childhood Hodgkin Lymphoma
• Stage III Childhood Hodgkin Lymphoma
• Stage IV Childhood Hodgkin Lymphoma

Intervention

Biological:
• Bleomycin Sulfate
Given IV or SC

Drug:
• Cisplatin
Given IV
• Cyclophosphamide
Given IV
• Cytarabine
Given IV
• Dexamethasone
Given IV
• Doxorubicin Hydrochloride
Given IV
• Etoposide
Given IV

Biological:
• Filgrastim
Given SC

Radiation:
• Involved-Field Radiation Therapy
Undergo IFRT

Drug:
• Prednisone
Given orally
• Vincristine Sulfate Liposome
Given IV

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Women's and Children's Hospital-Adelaide	North Adelaide	South Australia
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Chedoke Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Janeway Child Health Centre	Saint John's	Newfoundland and Labrador
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
Israel	Schneider Children's Medical Center of Israel	Petah Tikua
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Starship Children's Hospital	Grafton	Auckland
Puerto Rico	San Jorge Children's Hospital	San Juan
Switzerland	Swiss Pediatric Oncology Group - Geneva	Geneva
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	Texas Tech University Health Science Center-Amarillo	Amarillo	Texas
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Mission Hospital-Memorial Campus	Asheville	North Carolina
United States	Georgia Regents 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	Eastern Maine Medical Center	Bangor	Maine
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Brooklyn Hospital Center	Brooklyn	New York
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of Vermont College of Medicine	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	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	Palmetto Health Richland	Columbia	South Carolina
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
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	Blank Children's Hospital	Des Moines	Iowa
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Southern California Permanente Medical Group	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	Inova Fairfax Hospital	Falls Church	Virginia
United States	Sanford Medical Center-Fargo	Fargo	North Dakota
United States	Hurley Medical Center	Flint	Michigan
United States	Broward Health Medical Center	Fort Lauderdale	Florida
United States	Lee Memorial Health System	Fort Myers	Florida
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	University of Florida	Gainesville	Florida
United States	Saint Vincent Hospital	Green Bay	Wisconsin
United States	East Carolina University	Greenville	North Carolina
United States	Greenville Cancer Treatment Center	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida
United States	University of Hawaii Cancer Center	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	Indiana University/Melvin and Bren Simon Cancer Center	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	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan
United States	The Childrens Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of Kentucky/Markey Cancer Center	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Children's Hospital Central California	Madera	California
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Loyola University Medical Center	Maywood	Illinois
United States	Baptist Hospital of Miami	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	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Winthrop University 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	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	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	Columbia University/Herbert Irving Cancer Center	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Childrens Hospital-King's Daughters	Norfolk	Virginia
United States	Kaiser Permanente-Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	Florida Hospital Orlando	Orlando	Florida
United States	Nemours Children's Clinic - Orlando	Orlando	Florida
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
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 Hospital and Health Center	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Naval Medical Center - Portsmouth	Portsmouth	Virginia
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia
United States	Carilion Clinic Children's Hospital	Roanoke	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Cardinal Glennon Children's Medical Center	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Hospital	Salt Lake City	Utah
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	Rady Children's Hospital - San Diego	San Diego	California
United States	Santa Barbara Cottage Hospital	Santa Barbara	California
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	Overlook Hospital	Summit	New Jersey
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	Scott and White Memorial Hospital	Temple	Texas
United States	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio
United States	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	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	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Israel,  New Zealand,  Puerto Rico,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free survival defined as the time to treatment failure (disease progression, disease recurrence, biopsy positive residual after completion of all protocol therapy), occurrence of a second malignant neoplasm, or death from any cause		From study entry assessed up to 5 years	No
Secondary	Disease response assessed by modified RECIST criteria		Up to 5 years	No
Secondary	Incidence of Grade 3 or 4 non-hematologic toxicity that doesn't respond to treatment within 7 days despite recommended therapy modification assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0		Up to 5 years	Yes
Secondary	Overall survival		Up to 5 years	No