Treating Young Patients With Newly Diagnosed, Low Stage, Lymphocyte Predominant Hodgkin Disease

Ann Arbor Stage I Childhood Hodgkin Lymphoma Clinical Trial

Official title:

Treatment of Children With Newly-Diagnosed Low Stage Lymphocyte Predominant Hodgkin Disease (LPHD)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00107198
• Other study ID #: AHOD03P1
• Secondary ID: NCI-2009-00376AH
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 2, 2006
• Est. completion date: December 31, 2030

Study information

• Verified date: August 2023
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 188
• Est. completion date: December 31, 2030
• Est. primary completion date: October 6, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 21 Years

Eligibility

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

Related Conditions & MeSH terms

• Ann Arbor Stage I Childhood Hodgkin Lymphoma
• Ann Arbor Stage II Childhood Hodgkin Lymphoma
• Hodgkin Disease
• Lymphoma

Intervention

Procedure:
• Conventional Surgery
Undergo surgery

Drug:
• Cyclophosphamide
Given IV
• Doxorubicin Hydrochloride
Given IV
• Prednisone
Given IV or PO

Radiation:
• Radiation Therapy
Undergo IFRT

Drug:
• Vincristine Sulfate
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
Australia	The Children's Hospital at Westmead	Westmead	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
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	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
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 Sciences Center-Amarillo	Amarillo	Texas
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Emory University Hospital/Winship Cancer Institute	Atlanta	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	Children's Hospital of Alabama	Birmingham	Alabama
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
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 and State Agricultural College	Burlington	Vermont
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North 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	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	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	Dayton Children's Hospital	Dayton	Ohio
United States	Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center	Denver	Colorado
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	Inova Fairfax Hospital	Falls Church	Virginia
United States	University of Connecticut	Farmington	Connecticut
United States	Hurley Medical Center	Flint	Michigan
United States	Lee Memorial Health System	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	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan
United States	BI-LO Charities Children's Cancer Center	Greenville	South Carolina
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	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Children's Hospital	Hershey	Pennsylvania
United States	Penn State Milton S Hershey Medical Center	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	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	Cabell-Huntington Hospital	Huntington	West Virginia
United States	Indiana University/Melvin and Bren Simon Cancer Center	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	Kalamazoo Center for Medical Studies	Kalamazoo	Michigan
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
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	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Miller Children's and Women's Hospital Long Beach	Long Beach	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	Miami Cancer Institute	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	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota/Masonic Cancer Center	Minneapolis	Minnesota
United States	Morristown Medical Center	Morristown	New Jersey
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	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
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	UCSF Benioff Children's Hospital 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 Clinic - Orlando	Orlando	Florida
United States	Nemours Children's Hospital	Orlando	Florida
United States	Orlando Health Cancer Institute	Orlando	Florida
United States	Advocate Children's Hospital-Park Ridge	Park Ridge	Illinois
United States	Advocate Lutheran General Hospital	Park Ridge	Illinois
United States	Saint Joseph's Regional Medical Center	Paterson	New Jersey
United States	Sacred Heart Hospital	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	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	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Sutter Medical Center Sacramento	Sacramento	California
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	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	UCSF Medical Center-Mount Zion	San Francisco	California
United States	UCSF Medical Center-Parnassus	San Francisco	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	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Overlook Hospital	Summit	New Jersey
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Saint Joseph's Hospital/Children's Hospital-Tampa	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	Harbor-University of California at Los Angeles Medical Center	Torrance	California
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	New York Medical College	Valhalla	New York
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

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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure-free Survival (FFS)	The time to a treatment (strategy) failure, where failure includes one of the following occurrences as a first event: disseminated disease (> Stage I/II) progression or recurrence at any time, local disease progression or recurrence anytime during or after treatment with AV-PC +/- IFRT, occurrence of a second malignant neoplasm, death from any cause.	At 5 years
Secondary	Event-free Survival	Failure includes one of the following occurrences as a first event: relapse/progression or second malignancy from enrollment.	At 5 years
Secondary	Cure by Surgery Alone in Stage I Resected Patients	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.	At 2 years
Secondary	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	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 AV-PC x 3, with IFRT for those who are not in a CR after chemotherapy.	At 5 years
Secondary	Grade 3 or 4 Toxicity		Any time during chemoradiotherapy, up to the end of 3-cycles of AV-PC induction. Each cycle is 21 days.