Clinical trial NCT00059839: Comparison of Two Combination Chemotherapy Regimens With Either Vincristine or Vinblastine in Treating Patients With Advanced Anaplastic Large Cell Lymphoma
Official title: A Phase III Trial of Treatment of Advanced-Stage Anaplastic Large Cell Lymphoma (ALCL) With Standard APO (Doxorubicin, Prednisone, Vincristine) Versus Consolidation With a Regimen Including Vinblastine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma
Keywords: anaplastic large cell lymphoma
Lead sponsor: Children's Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-05-07
Enrollment: 129
Sex: ALL
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known if combination chemotherapy with vinblastine is more effective than combination chemotherapy with vincristine in treating advanced anaplastic large cell lymphoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens with either vinblastine or vincristine in treating patients who have newly diagnosed advanced anaplastic large cell lymphoma.

Detailed description: OBJECTIVES:

* Compare the efficacy of a consolidation chemotherapy regimen comprising doxorubicin and prednisone in combination with vincristine vs vinblastine, in terms of event-free survival, in patients with advanced anaplastic large cell lymphoma.
* Compare overall survival of patients treated with these regimens.
* Compare the toxic effects of these regimens in these patients.
* Correlate biological tumor characteristics and outcome in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study.

Patients are randomized at enrollment to receive either Standard APO regimen or a consolidation regimen including vinblastine (VBL).

* Induction therapy: All Patients receive doxorubicin IV over 15 minutes on days 1 and 22; vincristine IV on days 1, 8, 15, 22, and 29; oral prednisone 3 times daily on days 1-28; and intrathecal (IT) methotrexate on days 1, 8, and 22 (patients with central nervous system (CNS) disease at diagnosis receive additional methotrexate IT on days 15, 29, and 36).

Patients undergo restaging after Induction such that consolidation therapy is started on day 43. All patients with complete response (CR), complete response unconfirmed (CRu) or partial response (PR) proceed to Consolidation based on CT or MRI scans at the end of induction (week 6). All other patients will be removed from protocol therapy and will be followed until they meet the criteria for off study. Follow-up data will be required unless consent is withdrawn.

* Standard APO (Arm I): Patients receive course-specific regimens without vinblastine.

  * Courses 1-3: Patients receive doxorubicin IV over 15 minutes, vincristine IV, and methotrexate IT on day 1 and oral prednisone three times daily and oral mercaptopurine once daily on days 1-5.
  * Courses 4-5: Patients receive doxorubicin, vincristine, prednisone, and mercaptopurine as in courses 1-3.
  * Courses 6-15: Patients receive vincristine, prednisone, and mercaptopurine as in courses 1-3 and methotrexate IV on day 1.
* Consolidation with vinblastine (Arm II): Patients receive course-specific regimens including vinblastine.

  * Courses 1-3: Patients receive doxorubicin, methotrexate IT, prednisone, and mercaptopurine as in arm I and vinblastine IV over 1 minute on days 1, 8, and 15.
  * Courses 4-5: Patients receive doxorubicin, prednisone, and mercaptopurine as in arm I and vinblastine as in arm II (courses 1-3).
  * Courses 6-15: Patients receive prednisone and mercaptopurine as in arm I, vinblastine as in arm II (courses 1-3), and methotrexate IV on day 1.

In both arms and all courses, treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 200-250 patients (100-125 per treatment arm) will be accrued for this study within 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Newly diagnosed advanced anaplastic large cell lymphoma

  * Cluster of differentiation antigen 30 (CD30+)
  * Murphy stage III or IV
* No B-cell large cell lymphoma
* No disease limited to the skin (regardless of how wide-spread)

PATIENT CHARACTERISTICS:

Age

* Under 21

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* Not specified

Hepatic

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* Aspartate aminotransferase (AST) or alanine transaminase (ALT) less than 2.5 times ULN (unless due to lymphoma)

Renal

* Not specified

Cardiovascular

* Shortening fraction (SF) at least 27% by echocardiogram OR
* Ejection fraction (EF) at least 50% by radionuclide angiogram

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* Not specified

Endocrine therapy

* Prior steroids for management of a mediastinal mass allowed

Radiotherapy

* Prior limited-dose radiotherapy for a mediastinal mass allowed

Surgery

* Not specified

Primary outcomes:
measure: Event-free Survival (EFS)
timeFrame: From first enrollment up to 3 years.
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
state: Arkansas
city: Downey
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Cancer Institute at Loma Linda University Medical Center
state: California
city: Madera
country: United States
facility: Children's Hospital Central California
state: California
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Sacramento
country: United States
facility: Sutter Cancer Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Medical Center - Oakland
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 Helen Diller Family Comprehensive Cancer Center
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: Children's Hospital Center for Cancer and Blood Disorders
state: Colorado
city: Denver
country: United States
facility: Presbyterian - St. Luke's Medical Center
state: Colorado
city: Farmington
country: United States
facility: Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
state: Connecticut
city: Wilmington
country: United States
facility: Alfred I. duPont Hospital for Children
state: Delaware
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center Cancer Center
state: Florida
city: Fort Myers
country: United States
facility: Lee Cancer Care of Lee Memorial Health System
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center - Miami
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital
state: Florida
city: Miami
country: United States
facility: Baptist-South Miami Regional Cancer Program
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute at Florida Hospital Orlando
state: Florida
city: Orlando
country: United States
facility: M.D. Anderson Cancer Center at Orlando
state: Florida
city: Pensacola
country: United States
facility: Sacred Heart Cancer Center at Sacred Heart Hospital
state: Florida
city: St. Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Cancer Institute at St. Joseph's Hospital
state: Florida
city: West Palm Beach
country: United States
facility: Kaplan Cancer Center at St. Mary's Medical Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Augusta
country: United States
facility: MBCCOP - Medical College of Georgia Cancer Center
state: Georgia
city: Savannah
country: United States
facility: Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Honolulu
country: United States
facility: Cancer Research Center of Hawaii
state: Hawaii
city: Boise
country: United States
facility: Mountain States Tumor Institute at St. Luke's Regional Medical Center
state: Idaho
city: Chicago
country: United States
facility: Children's Memorial Hospital - Chicago
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Oak Lawn
country: United States
facility: Advocate Christ Medical Center
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Cancer Care Center
state: Illinois
city: Peoria
country: United States
facility: Saint Jude Midwest Affiliate
state: Illinois
city: Springfield
country: United States
facility: Simmons Cooper Cancer Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent Indianapolis Hospital
state: Indiana
city: Des Moines
country: United States
facility: Blank Children's Hospital
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: Alexandria
country: United States
facility: Tulane Cancer Center Office of Clinical Research
state: Louisiana
city: Baltimore
country: United States
facility: Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
state: Maryland
city: Boston
country: United States
facility: Floating Hospital for Children at Tufts - New England Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Regional Cancer Program at D'Amour Center for Cancer Care
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital at University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: CCOP - Kalamazoo
state: Michigan
city: Lansing
country: United States
facility: Breslin Cancer Center at Ingham Regional Medical Center
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota - Minneapolis
state: Minnesota
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Cancer Clinic
state: Mississippi
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Kansas City
country: United States
facility: Children's Mercy Hospital
state: Missouri
city: St. Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital
state: Nebraska
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Nevada Cancer Research Foundation
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center Cancer Center
state: New Jersey
city: Morristown
country: United States
facility: Overlook Hospital
state: New Jersey
city: New Brunswick
country: United States
facility: Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Hospital and Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Bronx
country: United States
facility: Albert Einstein Cancer Center at Albert Einstein College of Medicine
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: Schneider Children's Hospital
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Asheville
country: United States
facility: Mission Hospitals - Memorial Campus
state: North Carolina
city: Charlotte
country: United States
facility: Blumenthal Cancer Center at Carolinas Medical Center
state: North Carolina
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Greenville
country: United States
facility: Leo W. Jenkins Cancer Center at ECU Medical School
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Fargo
country: United States
facility: CCOP - MeritCare Hospital
state: North Dakota
city: Akron
country: United States
facility: Akron Children's Hospital
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 Children's Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Dayton
country: United States
facility: Children's Medical Center - Dayton
state: Ohio
city: Toledo
country: United States
facility: Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: Medical University of Ohio Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma University Cancer Institute
state: Oklahoma
city: Portland
country: United States
facility: Legacy Emanuel Hospital and Health Center and Children's Hospital
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University Cancer Institute
state: Oregon
city: Bethlehem
country: United States
facility: Lehigh Valley Hospital - Muhlenberg
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital Comprehensive Cancer Center
state: Rhode Island
city: Greenville
country: United States
facility: Greenville Hospital Cancer Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
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 Children's Hospital
state: Tennessee
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Amarillo
country: United States
facility: Texas Tech University Health Sciences Center School of Medicine - 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: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Houston
country: United States
facility: Baylor University Medical Center - Houston
state: Texas
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Lubbock
country: United States
facility: Covenant Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: San Antonio
country: United States
facility: Methodist Children's Hospital of South Texas
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Medical Center
state: Utah
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Carilion Medical Center for Children at Roanoke Community Hospital
state: Virginia
city: Seattle
country: United States
facility: Children's Hospital and Regional Medical Center - Seattle
state: Washington
city: Spokane
country: United States
facility: Providence Cancer Center at Sacred Heart Medical Center
state: Washington
city: Tacoma
country: United States
facility: Mary Bridge Children's Hospital and Health Center - Tacoma
state: Washington
city: Charleston
country: United States
facility: West Virginia University Health Sciences Center - Charleston
state: West Virginia
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Midwest Children's Cancer Center at Children's Hospital of Wisconsin
state: Wisconsin
city: Westmead
country: Australia
facility: Westmead Institute for Cancer Research at Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Children's Hospital
state: Queensland
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: Children's & Women's Hospital of British Columbia
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: St. John's
country: Canada
facility: Janeway Children's Health and Rehabilitation 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: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: Children's Hospital of Western Ontario
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: Montreal Children's Hospital at McGill University Health Center
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sainte Justine
state: Quebec
city: Regina
country: Canada
facility: Allan Blair Cancer Centre at Pasqua Hospital
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre at the University of Saskatchewan
state: Saskatchewan
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
city: Santurce
country: Puerto Rico
facility: San Jorge Children's Hospital
city: Bern
country: Switzerland
facility: Swiss Pediatric Oncology Group Bern
city: Geneva
country: Switzerland
facility: Swiss Pediatric Oncology Group Geneva
city: Lausanne
country: Switzerland
facility: Swiss Pediatric Oncology Group Lausanne
Study officials:
affiliation: Medical University of South Carolina
name: Jacqueline Kraveka, DO
role: STUDY_CHAIR
References:
citation: Alexander S, Kraveka JM, Weitzman S, Lowe E, Smith L, Lynch JC, Chang M, Kinney MC, Perkins SL, Laver J, Gross TG, Weinstein H. Advanced stage anaplastic large cell lymphoma in children and adolescents: results of ANHL0131, a randomized phase III trial of APO versus a modified regimen with vinblastine: a report from the children's oncology group. Pediatr Blood Cancer. 2014 Dec;61(12):2236-42. doi: 10.1002/pbc.25187. Epub 2014 Aug 23.