Clinical trial NCT00107198: Treating Young Patients With Newly Diagnosed, Low Stage, Lymphocyte Predominant Hodgkin Disease
Official title: Treatment of Children With Newly-Diagnosed Low Stage Lymphocyte Predominant Hodgkin Disease (LPHD)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Ann Arbor Stage I Childhood Hodgkin Lymphoma
Ann Arbor Stage II Childhood Hodgkin Lymphoma
Childhood Nodular Lymphocyte Predominant B-Cell Lymphoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-04-06
Enrollment: 188
Sex: ALL
Minimum age (years): 1
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This clinical trial is studying how well surgery and/or combination chemotherapy with or without radiation therapy or observation only work in treating young patients with newly diagnosed stage I or stage II lymphocyte predominant Hodgkin disease (LPHD). Surgery may be an effective treatment for LPHD. Drugs used in chemotherapy, such as doxorubicin, vincristine, prednisone, and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. Giving more than one drug (combination chemotherapy) with or without radiation therapy may kill more cancer cells.

Detailed description: PRIMARY OBJECTIVES:

I. To preserve the excellent cure rate in patients with lymphocyte predominant Hodgkin disease (LPHD) while employing a treatment strategy that minimizes the exposure to chemotherapy and radiation therapy in appropriate patients.

II. To estimate the proportion of stage I patients (with a single involved lymph node that is totally resected) who can be cured with surgery alone.

III. To estimate the proportions of stage I unresected, stage I resected (whose disease has recurred after observation), and stage II LPHD patients who can be cured with adriamycin (doxorubicin)/vincristine/prednisone/cyclophosphamide (AV-PC) x 3, with involved field radiation therapy (IFRT) for those who are not in a CR after chemotherapy.

IV. To reduce the potential for long-term toxicity of LPHD treatment.

OUTLINE: This is a pilot study.

Patients with stage IA disease who underwent confirmed complete resection of a single involved lymph node at diagnosis undergo observation only\*.

Patients with stage IA disease who underwent possible complete resection of a single involved lymph node at diagnosis undergo imaging at 6-7 weeks after surgery. Patients with a confirmed complete resection by imaging undergo observation only\*. Patients who do not demonstrate complete resection by imaging proceed to combination chemotherapy with or without radiotherapy.

Patients with stage IA disease who underwent a fine needle aspiration of a single involved lymph node OR an incomplete resection of a single involved lymph node at diagnosis may undergo a second surgery to achieve complete resection. Patients who undergo complete resection during the second surgery undergo imaging at 6-7 weeks after surgery. Patients with a confirmed complete resection by imaging undergo observation only\*. Patients who do not undergo a second surgery OR do not achieve complete resection with the second surgery proceed to combination chemotherapy with or without radiotherapy. Patients with stage IA disease with involvement of more than 1 lymph node OR stage IIA disease proceed directly to combination chemotherapy with or without radiotherapy.

NOTE: \*Patients with recurrent disease after observation only undergo biopsy and restaging and then proceed to combination chemotherapy with or without radiotherapy. (AS OF AMENDMENT #4, THE TREATMENT ARM FOR PATIENTS WHOSE CANCER RECURRED AFTER OBSERVATION ALONE IS NOW CLOSED)

COMBINATION CHEMOTHERAPY: Patients receive doxorubicin hydrochloride intravenously (IV) over 10-30 minutes and cyclophosphamide IV over 1 hour on day 1, vincristine IV over 1 minute on days 1 and 8, and prednisone orally (PO) or IV two or three times daily on days 1-7. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response (CR) after 3 courses of therapy proceed to follow-up. Patients who do not achieve a CR proceed to involved-field radiotherapy.

INVOLVED-FIELD RADIOTHERAPY (IFRT): Beginning within 3 weeks after completion of combination chemotherapy, patients undergo IFRT once daily, 5 days a week for 2.8 weeks (14 treatments).

Patients are followed every 3 months for 2 years, every 6 months for 3 years, annually for 5 years, and then every 5 years for 10 years.

Eligibility criteria: Inclusion Criteria:

* Patients with newly diagnosed, previously untreated, biopsy-proven lymphocyte predominant Hodgkin disease (LPHD) are eligible for this protocol as follows:

  * Diagnosis of LPHD must be made using the Revised European American Lymphoma (REAL)/World Health Organization (WHO) classification criteria and will be confirmed by rapid pathology central review
  * Clinical stages as follows:

    * Stage IA without bulk disease
    * Stage IIA without bulk disease
  * Patients with "B" symptoms or bulk disease are NOT eligible for this study
* Slides for rapid central pathology review must be sent to the Biopathology Center (BPC)
* Serum glutamic oxalo-acetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) \< 2.5 times upper limit of normal (ULN)
* Total bilirubin =\< 1.5 times ULN
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min
* Creatinine based on age/gender as follows:

  * No greater than 0.4 mg/dL (for patients 1 to 5 months of age)
  * No greater than 0.5 mg/dL (for patients 6 to 11 months of age)
  * No greater than 0.6 mg/dL (for patients 1 year of age)
  * No greater than 0.8 mg/dL (for patients 2 to 5 years of age)
  * No greater than 1.0 mg/dL (for patients 6 to 9 years of age)
  * No greater than 1.2 mg/dL (for patients 10 to 12 years of age)
  * No greater than 1.4 mg/dL (for female patients \>= 13 years of age)
  * No greater than 1.5 mg/dL (for male patients 13 to 15 years of age)
  * No greater than 1.7 mg/dL (for male patients \>= 16 years of age)
* Shortening fraction of \>= 27% by echocardiogram or ejection fraction of \>= 50% by multigated radionuclide angiogram (MUGA)
* Lactating females must agree that they will not breastfeed a child if they are to receive chemotherapy or radiation treatment\*
* Female patients of childbearing potential must have a negative pregnancy test if they are to receive chemotherapy or radiation treatment\*
* Males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method if they are to receive chemotherapy or radiation treatment\*
* Note: \*Pregnant or breastfeeding women with stage I, single involved lymph node and confirmed (by Quality Assurance Review Center \[QARC \]) total resection, are eligible for the observation arm only; no chemotherapy or radiation treatment will be administered to pregnant or breastfeeding women
* No prior chemotherapy
* More than 30 days since prior systemic corticosteroids
* No prior radiotherapy
* All patients and/or their parents or legal guardians must sign a written informed consent

Primary outcomes:
measure: Failure-free Survival (FFS)
timeFrame: At 5 years
Secondary outcomes:
measure: Event-free Survival
timeFrame: At 5 years
measure: Cure by Surgery Alone in Stage I Resected Patients
timeFrame: At 2 years
measure: Cure by AV-PC x 3 or AV-PC x 3 + IFRT for Stage I Unresected, Stage I Resected Whose Disease Recurred, and Stage II Patients
timeFrame: At 5 years
measure: Grade 3 or 4 Toxicity
timeFrame: Any time during chemoradiotherapy, up to the end of 3-cycles of AV-PC induction. Each cycle is 21 days.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Tucson
country: United States
facility: Banner University Medical Center - Tucson
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Downey
country: United States
facility: Kaiser Permanente Downey Medical Center
state: California
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Long Beach
country: United States
facility: Miller Children's and Women's Hospital Long Beach
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Oakland
country: United States
facility: Kaiser Permanente-Oakland
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Sacramento
country: United States
facility: Sutter Medical Center Sacramento
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Mount Zion
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center-Parnassus
state: California
city: Torrance
country: United States
facility: Harbor-University of California at Los Angeles Medical Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Denver
country: United States
facility: Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
state: Colorado
city: Farmington
country: United States
facility: University of Connecticut
state: Connecticut
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Myers
country: United States
facility: Lee Memorial Health System
state: Florida
city: Gainesville
country: United States
facility: University of Florida Health Science Center - Gainesville
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital/Joe DiMaggio Children's Hospital
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic-Jacksonville
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine-Sylvester Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Orlando
country: United States
facility: Arnold Palmer Hospital for Children
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Clinic - Orlando
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Pensacola
country: United States
facility: Sacred Heart Hospital
state: Florida
city: Saint Petersburg
country: United States
facility: Johns Hopkins All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: Saint Joseph's Hospital/Children's Hospital-Tampa
state: Florida
city: West Palm Beach
country: United States
facility: Saint Mary's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Savannah
country: United States
facility: Memorial Health University Medical Center
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Chicago
country: United States
facility: Lurie Children's Hospital-Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Children's Hospital-Oak Lawn
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Children's Hospital-Park Ridge
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Peoria
country: United States
facility: Saint Jude Midwest Affiliate
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University School of Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University/Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa/Holden Comprehensive Cancer Center
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky/Markey Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Children's Hospital
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: Sinai Hospital of Baltimore
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University/Sidney Kimmel Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: C S Mott Children's Hospital
state: Michigan
city: Detroit
country: United States
facility: Wayne State University/Karmanos Cancer Institute
state: Michigan
city: East Lansing
country: United States
facility: Michigan State University Clinical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Butterworth Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Bronson Methodist Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: Kalamazoo Center for Medical Studies
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota/Masonic Cancer Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital and Medical Center of Omaha
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Saint Peter's University Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
state: New Jersey
city: Paterson
country: United States
facility: Saint Joseph's Regional Medical Center
state: New Jersey
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Campus
state: New York
city: Brooklyn
country: United States
facility: Brooklyn Hospital Center
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New Hyde Park
country: United States
facility: The Steven and Alexandra Cohen Children's Medical Center of New York
state: New York
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas Medical Center/Levine Cancer Institute
state: North Carolina
city: Charlotte
country: United States
facility: Novant Health Presbyterian Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Akron
country: United States
facility: Children's Hospital Medical Center of Akron
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Childrens Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Dayton Children's Hospital
state: Ohio
city: Toledo
country: United States
facility: ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Portland
country: United States
facility: Legacy Emanuel Children's Hospital
state: Oregon
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Children's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Columbia
country: United States
facility: Prisma Health Richland Hospital
state: South Carolina
city: Greenville
country: United States
facility: BI-LO Charities Children's Cancer Center
state: South Carolina
city: Greenville
country: United States
facility: Greenville Cancer Treatment Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Chattanooga
country: United States
facility: T C Thompson Children's Hospital
state: Tennessee
city: Knoxville
country: United States
facility: East Tennessee Childrens Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University Health Sciences Center-Amarillo
state: Texas
city: Austin
country: United States
facility: Dell Children's Medical Center of Central Texas
state: Texas
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: Medical City Dallas Hospital
state: Texas
city: Dallas
country: United States
facility: UT Southwestern/Simmons Cancer Center-Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Covenant Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Burlington
country: United States
facility: University of Vermont and State Agricultural College
state: Vermont
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center and Children's Hospital
state: Washington
city: Charleston
country: United States
facility: West Virginia University Charleston Division
state: West Virginia
city: Huntington
country: United States
facility: Cabell-Huntington Hospital
state: West Virginia
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: North Adelaide
country: Australia
facility: Women's and Children's Hospital-Adelaide
state: South Australia
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John's
country: Canada
facility: Janeway Child Health Centre
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Children's Hospital at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Kingston Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier Universitaire Sainte-Justine
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
city: Quebec
country: Canada
facility: CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
city: Petah Tikua
country: Israel
facility: Schneider Children's Medical Center of Israel
city: Grafton
country: New Zealand
facility: Starship Children's Hospital
state: Auckland
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: San Juan
country: Puerto Rico
facility: San Jorge Children's Hospital
Study officials:
affiliation: Children's Oncology Group
name: Burton E Appel
role: PRINCIPAL_INVESTIGATOR
References: