Comparison of Two Combination Chemotherapy Regimens With Either Vincristine or Vinblastine in Treating Patients With Advanced Anaplastic Large Cell Lymphoma

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: doxorubicin hydrochloride; Drug: vincristine sulfate; Drug: mercaptopurine; Drug: methotrexate; Drug: prednisone; Drug: vinblastine sulfate

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.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Institute for Cancer Research at Westmead Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Royal Children's Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6001
      • Princess Margaret Hospital for Children
• Canada
  • Quebec, Canada, G1V 4G2
    • Centre Hospitalier Universitaire de Quebec
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
    • Edmonton, Alberta, Canada, T6G 1Z2
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • Children's & Women's Hospital of British Columbia
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
      • Janeway Children's Health and Rehabilitation Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster Children's Hospital at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 2V7
      • Cancer Centre of Southeastern Ontario At Kingston General Hospital
    • London, Ontario, Canada, N6A 5W9
      • Children's Hospital of Western Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H3H 1P3
      • Montreal Children's Hospital at McGill University Health Center
    • Montreal, Quebec, Canada, H3T 1C5
      • Hopital Sainte Justine
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre at Pasqua Hospital
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre at the University of Saskatchewan
• Puerto Rico
  • Santurce, Puerto Rico, 00912
    • San Jorge Children's Hospital
• Switzerland
  • Bern, Switzerland, 3010
    • Swiss Pediatric Oncology Group Bern
  • Geneva, Switzerland, 1205
    • Swiss Pediatric Oncology Group Geneva
  • Lausanne, Switzerland, 1011
    • Swiss Pediatric Oncology Group Lausanne
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
  • Arizona
    • Phoenix, Arizona, United States, 85016-7710
      • Phoenix Children's Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Downey, California, United States, 90027
      • Southern California Permanente Medical Group
    • Loma Linda, California, United States, 92354
      • Loma Linda University Cancer Institute at Loma Linda University Medical Center
    • Madera, California, United States, 93638-8762
      • Children's Hospital Central California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Sacramento, California, United States, 95816
      • Sutter Cancer center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Center - Oakland
    • San Diego, California, United States, 92123-4282
      • Rady Children's Hospital - San Diego
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
    • Stanford, California, United States, 94305-5824
      • Stanford Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Center for Cancer and Blood Disorders
    • Denver, Colorado, United States, 80218
      • Presbyterian - St. Luke's Medical Center
  • Connecticut
    • Farmington, Connecticut, United States, 06360-2875
      • Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I. DuPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2970
      • Children's National Medical Center
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center Cancer Center
    • Fort Myers, Florida, United States, 33901
      • Lee Cancer Care of Lee Memorial Health System
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute at Memorial Regional Hospital
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center - Miami
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital
    • Miami, Florida, United States, 33176
      • Baptist-South Miami Regional Cancer Program
    • Orlando, Florida, United States, 32803-1273
      • Florida Hospital Cancer Institute at Florida Hospital Orlando
    • Orlando, Florida, United States, 32806
      • M.D. Anderson Cancer Center at Orlando
    • Pensacola, Florida, United States, 32504
      • Sacred Heart Cancer Center at Sacred Heart Hospital
    • St. Petersburg, Florida, United States, 33701
      • All Children's Hospital
    • Tampa, Florida, United States, 33607
      • St. Joseph's Cancer Institute at St. Joseph's Hospital
    • West Palm Beach, Florida, United States, 33407
      • Kaplan Cancer Center at St. Mary's Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
    • Augusta, Georgia, United States, 30912-3730
      • MBCCOP - Medical College of Georgia Cancer Center
    • Savannah, Georgia, United States, 31403-3089
      • Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Cancer Research Center of Hawaii
  • Idaho
    • Boise, Idaho, United States, 83712-6297
      • Mountain States Tumor Institute at St. Luke's Regional Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital - Chicago
    • Oak Lawn, Illinois, United States, 60453
      • Advocate Christ Medical Center
    • Park Ridge, Illinois, United States, 60068-1174
      • Advocate Lutheran General Cancer Care Center
    • Peoria, Illinois, United States, 61637
      • Saint Jude Midwest Affiliate
    • Springfield, Illinois, United States, 62794-9677
      • Simmons Cooper Cancer Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5289
      • Indiana University Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent Indianapolis Hospital
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Blank Children's Hospital
    • Iowa City, Iowa, United States, 52242-1002
      • Holden Comprehensive Cancer Center at University of Iowa
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
    • Louisville, Kentucky, United States, 40232
      • Kosair Children's Hospital
  • Louisiana
    • Alexandria, Louisiana, United States, 71315-3198
      • Tulane Cancer Center Office of Clinical Research
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02111
      • Floating Hospital for Children at Tufts - New England Medical Center
    • Springfield, Massachusetts, United States, 01199-0001
      • Baystate Regional Cancer Program at D'Amour Center for Cancer Care
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0286
      • C.S. Mott Children's Hospital at University of Michigan Medical Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Grand Rapids, Michigan, United States, 49503-2560
      • Butterworth Hospital at Spectrum Health
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Kalamazoo, Michigan, United States, 49007-5381
      • CCOP - Kalamazoo
    • Lansing, Michigan, United States, 48910
      • Breslin Cancer Center at Ingham Regional Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota - Minneapolis
    • Minneapolis, Minnesota, United States, 55455
      • Masonic Cancer Center at University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216-4505
      • University of Mississippi Cancer Clinic
  • Missouri
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center at University of Missouri - Columbia
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
    • St. Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68114-4113
      • Children's Hospital
    • Omaha, Nebraska, United States, 68198-6805
      • UNMC Eppley Cancer Center at the University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89109-2306
      • CCOP - Nevada Cancer Research Foundation
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center Cancer Center
    • Morristown, New Jersey, United States, 07962
      • Overlook Hospital
    • New Brunswick, New Jersey, United States, 08903
      • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Medical Center
    • Paterson, New Jersey, United States, 07503
      • St. Joseph's Hospital and Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Center
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein Cancer Center at Albert Einstein College of Medicine
    • Brooklyn, New York, United States, 11201-5493
      • Brooklyn Hospital Center
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • New Hyde Park, New York, United States, 11040
      • Schneider Children's Hospital
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University Hospital
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospitals - Memorial Campus
    • Charlotte, North Carolina, United States, 28232-2861
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Cancer Center at Presbyterian Hospital
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Greenville, North Carolina, United States, 27835-6028
      • Leo W. Jenkins Cancer Center at ECU Medical School
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • CCOP - MeritCare Hospital
  • Ohio
    • Akron, Ohio, United States, 44308-1062
      • Akron Children's Hospital
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106-5000
      • Rainbow Babies and Children's Hospital
    • Columbus, Ohio, United States, 43205-2696
      • Nationwide Children's Hospital
    • Dayton, Ohio, United States, 45404-1815
      • Children's Medical Center - Dayton
    • Toledo, Ohio, United States, 43606
      • Toledo Hospital
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Hospital and Health Center and Children's Hospital
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health and Science University Cancer Institute
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • Danville, Pennsylvania, United States, 17822-0001
      • Geisinger Cancer Institute at Geisinger Health
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Cancer Institute at Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19134-1095
      • St. Christopher's Hospital for Children
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital Comprehensive Cancer Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital Cancer Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Cancer Center at Sanford USD Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • T.C. Thompson Children's Hospital
    • Knoxville, Tennessee, United States, 37901
      • East Tennessee Children's Hospital
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children'S Research Hospital
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech University Health Sciences Center School of Medicine - Amarillo
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center of Central Texas
    • Corpus Christi, Texas, United States, 78411
      • Driscoll Children's Hospital
    • Dallas, Texas, United States, 75230
      • Medical City Dallas Hospital
    • Dallas, Texas, United States, 75390
      • Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center - Fort Worth
    • Houston, Texas, United States, 77030-4009
      • M. D. Anderson Cancer Center at University of Texas
    • Houston, Texas, United States, 77030-2399
      • Baylor University Medical Center - Houston
    • Lubbock, Texas, United States, 79410
      • Covenant Children's Hospital
    • San Antonio, Texas, United States, 78229-3993
      • Methodist Children's Hospital of South Texas
    • San Antonio, Texas, United States, 78207
      • University of Texas Health Science Center at San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84113-1100
      • Primary Children's Medical Center
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care - University Health Center Campus
  • Virginia
    • Norfolk, Virginia, United States, 23507-1971
      • Children's Hospital of The King's Daughters
    • Richmond, Virginia, United States, 23298-0037
      • Virginia Commonwealth University Massey Cancer Center
    • Roanoke, Virginia, United States, 24014
      • Carilion Medical Center for Children at Roanoke Community Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Children's Hospital and Regional Medical Center - Seattle
    • Spokane, Washington, United States, 99220-2555
      • Providence Cancer Center at Sacred Heart Medical Center
    • Tacoma, Washington, United States, 98405
      • Mary Bridge Children's Hospital and Health Center - Tacoma
  • West Virginia
    • Charleston, West Virginia, United States, 25302
      • West Virginia University Health Sciences Center - Charleston
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54307-3508
      • St. Vincent Hospital Regional Cancer Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center
    • Milwaukee, Wisconsin, United States, 53226
      • Midwest Children's Cancer Center at Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 20 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard APO with Vincristine (Arm I ); In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV over 15 minutes, vincristine sulfate (1.5 mg/m2 (maximum dose 2 mg)) IV, and methotrexate intrathecally (age-adjusted dosing) (IT) on day 1 and oral prednisone (40 mg/m2/day) three times daily and oral mercaptopurine (225 mg/m2) once daily on days 1-5. In courses 4 and 5, patients receive doxorubicin (30 mg/m2), vincristine sulfate (1.5 mg/m2 (Maximum dose 2 mg)), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3. In courses 6-15, patients receive vincristine sulfate (1.5 mg/m2), prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in courses 1-3 and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.	Drug: doxorubicin hydrochloride; Given IV; Drug: vincristine sulfate; Given IV; Drug: mercaptopurine; Given by mouth; Drug: methotrexate; Given IV and intrathecally; Drug: prednisone; Given by mouth
Experimental: Consolidation with Vinblastine; In courses 1-3, patients receive doxorubicin hydrochloride (30 mg/m2) IV, methotrexate (age adjusted dosing) IT, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) IV over 1 minute on days 1, 8, and 15. In courses 4 and 5, patients receive doxorubicin hydrochloride (30 mg/m2) IV, prednisone (120 mg/m2/day), and mercaptopurine (225 mg/m2) as in arm I and vinblastine sulfate (4 mg/m2) as in arm II (courses 1-3). In courses 6-15, patients receive prednisone (120 mg/m2/day) and mercaptopurine (225 mg/m2) as in arm I, vinblastine sulfate (4 mg/m2) IV as in arm II (courses 1-3), and methotrexate (60 mg/m2) IV on day 1. Treatment repeats every 21 days for up to 15 courses in the absence of disease progression or unacceptable toxicity.	Drug: doxorubicin hydrochloride; Given IV; Drug: mercaptopurine; Given by mouth; Drug: methotrexate; Given IV and intrathecally; Drug: prednisone; Given by mouth; Drug: vinblastine sulfate; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free Survival (EFS)	Percentage of EFS patients. This is measured as the time from study entry until disease progression, disease recurrence, occurrence of a second malignant neoplasm, or death from any cause. To measure Event Free Survival, repeated one-sided logrank tests will be performed The upper critical values are based on the one-sided alpha-spending functions of t2 (alpha=0.05) and the lower critical values are based on testing the alternative hypothesis at 0.005 level.	From first enrollment up to 3 years.

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Jacqueline Kraveka, DO, Medical University of South Carolina

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2003
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: May 6, 2003
• First Submitted That Met QC Criteria: May 6, 2003
• First Posted (Estimate): May 7, 2003

Study Record Updates

• Last Update Posted (Estimate): September 22, 2014
• Last Update Submitted That Met QC Criteria: September 10, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: anaplastic large cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma; Lymphoma, Large-Cell, Anaplastic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Antibiotics, Antineoplastic; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Prednisone; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Mercaptopurine; Vinblastine
• Other Study ID Numbers: ANHL0131; CDR0000298777 (Other Identifier: Clinical Trials.gov); COG-ANHL0131 (Other Identifier: Children's Oncology Group)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No