Skip to main content

Combination Chemotherapy with or without Rituximab in Treating Younger Patients with Stage III-IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia

Trial Status: Complete

This randomized phase II / III trial studies how well combination chemotherapy with or without rituximab works in treating younger patients with stage III-IV non-Hodgkin lymphoma or B-cell acute leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibody, such as rituximab, may block cancer growth in different ways by targeting certain cells. It is not yet known whether combination chemotherapy together with rituximab is more effective in treating patients with non-Hodgkin lymphoma or B-cell acute leukemia.

Inclusion Criteria

  • Histologically or cytologically proven B-cell malignancies; either Burkitt leukemia or B-AL (= Burkitt leukemia = L3-AL), or diffuse large B-cell NHL, or aggressive mature B-cell NHL non otherwise specified or specifiable (phase III) * Stage III with elevated LDH level (B-high) (LDH > twice the institutional upper limit of the adult normal values [> Nx2]), any stage IV, or B-AL (phase III)
  • Histolo-cytologically proven PMLBL (phase II) * PMLBL without central nervous system (CNS) involvement * Slides will be reviewed by the national pathology panel, but review is not mandatory before registration
  • Males and females of reproductive potential must agree to use an effective contraceptive method during the treatment, and after the end of treatment: during twelve months for women, taking into account the characteristics of rituximab and during five months for men, taking into account the characteristics of methotrexate
  • Complete initial work-up within 8 days prior to treatment that allows definite staging
  • Able to comply with scheduled follow-up and with management of toxicity
  • Signed informed consent from patients and/or their parents or legal guardians

Exclusion Criteria

  • Follicular lymphoma, Mucosa-Associated Lymphoid Tissue (MALT) and nodular marginal zone are not included into this therapeutic study
  • In phase II study (PMLBL) patients with CNS involvement are not eligible
  • Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive human immunodeficiency virus (HIV) serology
  • Evidence of pregnancy or lactation period
  • There will be no exclusion criteria based on organ function
  • Past or current anti-cancer treatment except corticosteroids of less than 7 days duration in total
  • Tumor cell negative for cluster of differentiation (CD)20 (absence of result due to technical problems in the presence of other characteristics suggestive of BL/DLBCL, including genetic and phenotypic features, is not an exclusion criteria)
  • Prior exposure to rituximab
  • Severe active viral infection, especially hepatitis B; severe infection (such as sepsis, pneumonia, etc.) should be clinically controlled at the time of randomization; contact the national co-investigator for further advice if necessary
  • Hepatitis B carrier status history of hepatitis B virus (HBV) or positive serology; a patient is considered as HBV carrier or to have (had) HBV infection in case of: * Unimmunized and hepatitis B surface antigen (HBsAg) and/or anti-HBs antibody and/or anti- HBc antibody positive, * Immunized and HBsAG and/or anti-HBc antibody positive ** Important note: for the phase III trial, a patient without a known history of hepatitis B could be randomized in the study if the serology results are not available at the time of the randomization; however, if the serology results are positive or not available at day 6 (the first day would be due to receive rituximab, if so randomized), the patient must be withdrawn from the study whatever the allocated treatment arm; the data center must be informed immediately; for the phase II trial, the hepatitis B serology results must be available before registration; in each case indicating a carrier status or history for hepatitis B infection, the patients must not receive rituximab, and therefore must not be included in the rituximab trials on any treatment arm; in case of high-risk patients, the recommendation is to treat these patients with the standard LMB regimen corresponding to the patient prognostic group; in the case of PMLBL the physician is left to choose the most appropriate therapy
  • Participation in another investigational drug clinical trial
  • Patients who, for any reason, are not able to comply with the national legislation

Alabama

Birmingham
Children's Hospital of Alabama
Status: CLOSED_TO_ACCRUAL
Contact: Alyssa Terry Reddy
Mobile
USA Health Strada Patient Care Center
Status: COMPLETED
Contact: Felicia Little Wilson
Phone: 251-665-8000

Arizona

Phoenix
Phoenix Childrens Hospital
Status: COMPLETED
Contact: Jessica Boklan
Phone: 602-546-0920

Arkansas

Little Rock
Arkansas Children's Hospital
Status: COMPLETED
Contact: David L. Becton
Phone: 501-364-7373
University of Arkansas for Medical Sciences
Status: CLOSED_TO_ACCRUAL
Contact: David L. Becton
Phone: 501-364-7373

California

Downey
Kaiser Permanente Downey Medical Center
Status: COMPLETED
Contact: Robert Michael Cooper
Phone: 626-564-3455
Duarte
City of Hope Comprehensive Cancer Center
Status: COMPLETED
Contact: Theresa Marie Harned
Phone: 626-564-3455
Loma Linda
Loma Linda University Medical Center
Status: COMPLETED
Contact: Albert Kheradpour
Phone: 909-558-3375
Long Beach
Miller Children's and Women's Hospital Long Beach
Status: COMPLETED
Contact: Pamela Helen-heilge Kempert
Phone: 562-933-5600
Los Angeles
Cedars Sinai Medical Center
Status: COMPLETED
Contact: Fataneh (Fae) Majlessipour
Phone: 310-423-8965
Children's Hospital Los Angeles
Status: COMPLETED
Contact: Leo Mascarenhas
Phone: 323-361-4110
Oakland
Kaiser Permanente-Oakland
Status: COMPLETED
Contact: Steven K. Bergstrom
Phone: 626-564-3455
UCSF Benioff Children's Hospital Oakland
Status: COMPLETED
Contact: Carla Barbara Golden
Phone: 510-450-7600
Orange
Children's Hospital of Orange County
Status: COMPLETED
Contact: Violet Shen
Phone: 714-997-3000
Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: COMPLETED
Contact: Neyssa Maria Marina
Phone: 650-498-7061
Sacramento
Sutter Medical Center Sacramento
Status: COMPLETED
Contact: Yung Soon Yim
Phone: 415-209-2686
University of California Davis Comprehensive Cancer Center
Status: COMPLETED
Contact: Marcio Henrique Malogolowkin
Phone: 916-734-3089
San Diego
Rady Children's Hospital - San Diego
Status: COMPLETED
Contact: William D. Roberts
Phone: 858-966-5934
San Francisco
UCSF Medical Center-Mission Bay
Status: COMPLETED
Contact: Michelle Lynn Hermiston
Phone: 877-827-3222
UCSF Medical Center-Parnassus
Status: CLOSED_TO_ACCRUAL
Contact: Michelle Lynn Hermiston
Phone: 877-827-3222
Torrance
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Status: COMPLETED
Contact: Joseph L. Lasky
Phone: 888-662-8252

Colorado

Aurora
Children's Hospital Colorado
Status: COMPLETED
Contact: Kelly Wilson Maloney
Phone: 720-777-6672
Denver
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Status: COMPLETED
Contact: Jennifer Jocelyn Clark
Phone: 866-775-6246

Connecticut

Hartford
Connecticut Children's Medical Center
Status: COMPLETED
Contact: Michael Scott Isakoff
Phone: 860-545-9981
New Haven
Yale University
Status: COMPLETED
Contact: Nina Singh Kadan-Lottick
Phone: 203-785-5702

Delaware

Wilmington
Alfred I duPont Hospital for Children
Status: COMPLETED
Contact: Jeffrey H. Schwartz
Phone: 904-697-3529

District of Columbia

Washington
Children's National Medical Center
Status: COMPLETED
Contact: Jeffrey Stuart Dome
Phone: 202-884-2549
MedStar Georgetown University Hospital
Status: COMPLETED
Contact: Aziza Tahir Shad
Phone: 202-444-0381

Florida

Fort Myers
Golisano Children's Hospital of Southwest Florida
Status: COMPLETED
Contact: Emad K. Salman
Phone: 239-343-5333
Lee Memorial Health System
Status: CLOSED_TO_ACCRUAL
Contact: Emad K. Salman
Phone: 239-343-5333
Gainesville
University of Florida Health Science Center - Gainesville
Status: COMPLETED
Contact: William Birdsall Slayton
Phone: 352-273-8675
Hollywood
Memorial Regional Hospital / Joe DiMaggio Children's Hospital
Status: COMPLETED
Contact: Iftikhar Hanif
Phone: 954-265-2234
Jacksonville
Nemours Children's Clinic-Jacksonville
Status: COMPLETED
Contact: Jeffrey H. Schwartz
Phone: 904-697-3529
Miami
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: COMPLETED
Contact: Julio Cesar Barredo
Phone: 866-574-5124
Orlando
AdventHealth Orlando
Status: COMPLETED
Contact: Fouad M. Hajjar
Phone: 407-303-5623
Arnold Palmer Hospital for Children
Status: COMPLETED
Contact: Vincent Ferdinando Giusti
Phone: 321-841-7246
Nemours Children's Hospital
Status: COMPLETED
Contact: Jeffrey H. Schwartz
Phone: 904-697-3529
Orlando Health Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Vincent Ferdinando Giusti
Phone: 321-841-7246
Pensacola
Nemours Children's Clinic - Pensacola
Status: COMPLETED
Contact: Jeffrey H. Schwartz
Phone: 904-697-3529
Saint Petersburg
Johns Hopkins All Children's Hospital
Status: COMPLETED
Contact: Gregory Alan Hale
Phone: 727-767-2423
Tampa
Tampa General Hospital
Status: COMPLETED
Contact: Cameron K. Tebbi
Phone: 800-882-4123
West Palm Beach
Saint Mary's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Narayana Gowda

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: COMPLETED
Contact: Glen Lew
Phone: 404-785-1112
Augusta
Augusta University Medical Center
Status: COMPLETED
Contact: Colleen H. McDonough
Phone: 706-721-1663
Savannah
Memorial Health University Medical Center
Status: COMPLETED
Contact: J. Martin Johnston
Phone: 912-350-8568

Hawaii

Honolulu
Kapiolani Medical Center for Women and Children
Status: COMPLETED
Contact: Robert W. Wilkinson
Phone: 808-983-6090
University of Hawaii Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Robert W. Wilkinson
Phone: 808-983-6090

Idaho

Boise
Saint Luke's Cancer Institute - Boise
Status: COMPLETED
Contact: Eugenia Chang
Phone: 800-845-4624

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: COMPLETED
Contact: Joanna Lynn Weinstein
Phone: 773-880-4562
University of Illinois
Status: COMPLETED
Contact: Mary Lou Schmidt
Phone: 312-355-3046
Maywood
Loyola University Medical Center
Status: COMPLETED
Contact: Eugene Suh
Phone: 708-226-4357
Oak Lawn
Advocate Children's Hospital-Oak Lawn
Status: COMPLETED
Contact: Rebecca Erin McFall
Phone: 847-723-7570
Peoria
Saint Jude Midwest Affiliate
Status: COMPLETED
Contact: Karen Sofia Fernandez
Phone: 309-655-3258
Springfield
Southern Illinois University School of Medicine
Status: COMPLETED
Contact: Gregory P. Brandt
Phone: 217-545-7929

Indiana

Indianapolis
Riley Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Robert J. Fallon
Phone: 800-248-1199
Saint Vincent Hospital and Health Care Center
Status: COMPLETED
Contact: Bassem I. Razzouk
Phone: 317-338-2194

Iowa

Des Moines
Blank Children's Hospital
Status: COMPLETED
Contact: Wendy Leigh Woods-Swafford
Phone: 515-241-6729
Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: COMPLETED
Contact: Ayman Aly El-Sheikh
Phone: 800-237-1225

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: COMPLETED
Contact: Lars Martin Wagner
Phone: 859-257-3379
Louisville
Norton Children's Hospital
Status: COMPLETED
Contact: Kenneth G. Lucas
Phone: 866-530-5516

Louisiana

New Orleans
Children's Hospital New Orleans
Status: COMPLETED
Contact: Lolie C. Yu
Phone: 504-894-5377
Ochsner Medical Center Jefferson
Status: COMPLETED
Contact: Craig Lotterman
Phone: 888-562-4763

Maine

Scarborough
Maine Children's Cancer Program
Status: CLOSED_TO_ACCRUAL
Contact: Aaron Robert Weiss

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: COMPLETED
Contact: Kenneth J. Cohen
Phone: 410-955-8804
Sinai Hospital of Baltimore
Status: COMPLETED
Contact: Joseph M. Wiley
Phone: 410-601-6120
University of Maryland / Greenebaum Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Teresa Anne York
Phone: 800-888-8823
Bethesda
Walter Reed National Military Medical Center
Status: COMPLETED
Contact: Anne Benedicta Warwick
Phone: 301-319-2100

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: COMPLETED
Contact: Suzanne Shusterman
Phone: 877-442-3324
Massachusetts General Hospital Cancer Center
Status: COMPLETED
Contact: Suzanne Shusterman
Phone: 877-442-3324
Tufts Children's Hospital
Status: COMPLETED
Contact: Michael J. Kelly
Phone: 617-636-5000
Springfield
Baystate Medical Center
Status: COMPLETED
Contact: Joanna G. Luty
Phone: 413-794-3565
Worcester
UMass Memorial Medical Center - University Campus
Status: COMPLETED
Contact: Christopher P. Keuker
Phone: 508-856-3216

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: COMPLETED
Contact: Rajen Mody
Phone: 800-865-1125
Detroit
Ascension Saint John Hospital
Status: COMPLETED
Contact: Hadi Sawaf
Phone: 313-343-3166
Wayne State University / Karmanos Cancer Institute
Status: COMPLETED
Contact: Meret Henry
Phone: 313-576-9363
East Lansing
Michigan State University Clinical Center
Status: COMPLETED
Contact: Renuka Gera
Phone: 517-975-9547
Grand Rapids
Helen DeVos Children's Hospital at Spectrum Health
Status: COMPLETED
Contact: David Scott Dickens
Phone: 616-267-1925

Minnesota

Minneapolis
Children's Hospitals and Clinics of Minnesota - Minneapolis
Status: CLOSED_TO_ACCRUAL
Contact: Michael Kerr Richards
Phone: 612-813-5193
Rochester
Mayo Clinic in Rochester
Status: COMPLETED
Contact: Paul John Galardy
Phone: 507-538-7623

Mississippi

Jackson
University of Mississippi Medical Center
Status: COMPLETED
Contact: Gail Cranshaw Megason
Phone: 601-815-6700

Missouri

Columbia
Columbia Regional
Status: COMPLETED
Contact: Thomas Ward Loew
Phone: 573-882-7440
University of Missouri - Ellis Fischel
Status: WITHDRAWN
Contact: Thomas Ward Loew
Phone: 573-882-7440
Kansas City
Children's Mercy Hospitals and Clinics
Status: COMPLETED
Contact: Maxine Lorraine Hetherington
Phone: 816-234-3265
Saint Louis
Mercy Hospital Saint Louis
Status: COMPLETED
Contact: Bethany Graham Sleckman
Phone: 913-948-5588
Washington University School of Medicine
Status: COMPLETED
Contact: Robert J. Hayashi
Phone: 800-600-3606

Nebraska

Omaha
Children's Hospital and Medical Center of Omaha
Status: COMPLETED
Contact: Minnie Abromowitch
Phone: 402-955-3949
University of Nebraska Medical Center
Status: COMPLETED
Contact: Minnie Abromowitch
Phone: 402-955-3949

Nevada

Las Vegas
Alliance for Childhood Diseases / Cure 4 the Kids Foundation
Status: COMPLETED
Contact: Jonathan Bernstein
Phone: 702-384-0013
Nevada Cancer Research Foundation NCORP
Status: CLOSED_TO_ACCRUAL
Contact: Nik Farahana Nik Abdul Rashid
Phone: 702-384-0013
University Medical Center of Southern Nevada
Status: COMPLETED
Contact: Jonathan Bernstein
Phone: 702-384-0013

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: COMPLETED
Contact: Sara Chaffee
Phone: 800-639-6918

New Jersey

Hackensack
Hackensack University Medical Center
Status: COMPLETED
Contact: Burton Eliot Appel
Phone: 201-996-2879
Morristown
Morristown Medical Center
Status: COMPLETED
Contact: Steven Lon Halpern
Phone: 973-971-5900
New Brunswick
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
Status: COMPLETED
Contact: Richard A. Drachtman
Phone: 732-235-8675
Newark
Newark Beth Israel Medical Center
Status: COMPLETED
Contact: Peri Kamalakar
Phone: 973-926-7230
Paterson
Saint Joseph's Regional Medical Center
Status: COMPLETED
Contact: Mary Ann Bonilla
Phone: 973-754-2909

New Mexico

Albuquerque
University of New Mexico Cancer Center
Status: COMPLETED
Contact: Koh B. Boayue
Phone: 505-272-6972

New York

Albany
Albany Medical Center
Status: COMPLETED
Contact: Vikramjit Singh Kanwar
Phone: 518-262-3368
Bronx
Montefiore Medical Center - Moses Campus
Status: COMPLETED
Contact: Peter David Cole
Phone: 718-904-2730
Buffalo
Roswell Park Cancer Institute
Status: COMPLETED
Contact: Martin Louis Brecher
Phone: 877-275-7724
Mineola
NYU Winthrop Hospital
Status: COMPLETED
Contact: Mark E. Weinblatt
Phone: 866-946-8476
New York
Mount Sinai Hospital
Status: COMPLETED
Contact: Birte Wistinghausen
Phone: 212-824-7320
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: COMPLETED
Contact: Alice Lee
Phone: 212-305-8615
NYP / Weill Cornell Medical Center
Status: COMPLETED
Contact: Lisa Giulino Roth
Phone: 212-746-1848
Syracuse
State University of New York Upstate Medical University
Status: COMPLETED
Contact: Karol Hicks Kerr
Phone: 315-464-5476

North Carolina

Asheville
Mission Hospital
Status: COMPLETED
Contact: Douglas James Scothorn
Phone: 828-213-4150
Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: COMPLETED
Contact: Stuart Harrison Gold
Phone: 877-668-0683
Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: COMPLETED
Contact: Joel A. Kaplan
Phone: 704-355-2884
Novant Health Presbyterian Medical Center
Status: COMPLETED
Contact: Paulette Charese Bryant
Phone: 704-384-5369
Durham
Duke University Medical Center
Status: COMPLETED
Contact: Susan G. Kreissman
Phone: 888-275-3853
Winston-Salem
Wake Forest University Health Sciences
Status: COMPLETED
Contact: Thomas Bennett Russell
Phone: 336-713-6771

Ohio

Akron
Children's Hospital Medical Center of Akron
Status: COMPLETED
Contact: Steven J. Kuerbitz
Phone: 330-543-3193
Cincinnati
Cincinnati Children's Hospital Medical Center
Status: COMPLETED
Contact: John Peter Perentesis
Phone: 513-636-2799
Cleveland
Cleveland Clinic Foundation
Status: COMPLETED
Contact: Aron Flagg
Phone: 866-223-8100
Rainbow Babies and Childrens Hospital
Status: COMPLETED
Contact: Yousif (Joe) H. Matloub
Phone: 216-844-5437
Columbus
Nationwide Children's Hospital
Status: COMPLETED
Contact: Mark Anthony Ranalli
Phone: 614-722-2708
Dayton
Dayton Children's Hospital
Status: COMPLETED
Contact: Ayman Aly El-Sheikh
Phone: 800-237-1225
Toledo
Mercy Children's Hospital
Status: COMPLETED
Contact: Rama Jasty
Phone: 419-251-8210

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: COMPLETED
Contact: Rene Y McNall-Knapp
Phone: 405-271-4272

Oregon

Portland
Legacy Emanuel Children's Hospital
Status: COMPLETED
Contact: Janice Faye Olson
Phone: 503-413-2560
Oregon Health and Science University
Status: COMPLETED
Contact: Linda Claudette Stork
Phone: 503-494-1080

Pennsylvania

Bethlehem
Lehigh Valley Hospital - Muhlenberg
Status: COMPLETED
Contact: Philip M. Monteleone
Phone: 484-884-2201
Danville
Geisinger Medical Center
Status: COMPLETED
Contact: Jagadeesh Ramdas
Phone: 570-271-5251
Hershey
Penn State Children's Hospital
Status: COMPLETED
Contact: Lisa MacNabb McGregor
Phone: 717-531-6012
Philadelphia
Children's Hospital of Philadelphia
Status: COMPLETED
Contact: Anne Fitzpatrick Reilly
Phone: 215-590-2810
Saint Christopher's Hospital for Children
Status: COMPLETED
Contact: Akash Nahar
Phone: 215-427-8991
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: COMPLETED
Contact: Peter H. Shaw
Phone: 412-692-5573

Rhode Island

Providence
Rhode Island Hospital
Status: COMPLETED
Contact: Jennifer J. Greene Welch
Phone: 401-444-1488

South Carolina

Charleston
Medical University of South Carolina
Status: COMPLETED
Contact: Jacqueline M. Kraveka
Phone: 843-792-9321
Columbia
Prisma Health Richland Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Ronnie W. Neuberg
Phone: 803-434-3680
Greenville
BI-LO Charities Children's Cancer Center
Status: COMPLETED
Contact: Nichole Leigh Bryant
Phone: 864-241-6251

South Dakota

Sioux Falls
Sanford USD Medical Center - Sioux Falls
Status: COMPLETED
Contact: Kayelyn Jean Wagner
Phone: 605-328-1367

Tennessee

Chattanooga
T C Thompson Children's Hospital
Status: COMPLETED
Contact: Manoo G. Bhakta
Phone: 423-778-7289
Knoxville
East Tennessee Childrens Hospital
Status: COMPLETED
Contact: Ray C. Pais
Phone: 865-541-8266
Nashville
Vanderbilt University / Ingram Cancer Center
Status: COMPLETED
Contact: Debra L Friedman
Phone: 800-811-8480

Texas

Austin
Dell Children's Medical Center of Central Texas
Status: COMPLETED
Contact: Amy Fowler Tellinghuisen
Phone: 214-648-7097
Corpus Christi
Driscoll Children's Hospital
Status: COMPLETED
Contact: M. Cris Johnson
Phone: 361-694-5311
Dallas
Medical City Dallas Hospital
Status: COMPLETED
Contact: Stanton Carl Goldman
Phone: 972-566-5588
UT Southwestern / Simmons Cancer Center-Dallas
Status: COMPLETED
Contact: Martha Marie Pacheco
Phone: 214-648-7097
El Paso
El Paso Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Lisa Louise Rubin Hartman
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: COMPLETED
Contact: Kala Y. Kamdar
Phone: 713-798-1354
Lubbock
Covenant Children's Hospital
Status: COMPLETED
Contact: Latha Prasannan
Phone: 806-725-8000
San Antonio
Children's Hospital of San Antonio
Status: CLOSED_TO_ACCRUAL
Contact: Timothy C. Griffin
Phone: 800-248-1199
Methodist Children's Hospital of South Texas
Status: CLOSED_TO_ACCRUAL
Contact: Gerardo Quezada
Temple
Scott and White Memorial Hospital
Status: COMPLETED
Contact: Guy Howard Grayson
Phone: 254-724-5407

Utah

Salt Lake City
Primary Children's Hospital
Status: COMPLETED
Contact: Phillip Evan Barnette
Phone: 801-585-5270

Virginia

Charlottesville
University of Virginia Cancer Center
Status: COMPLETED
Contact: Kimberly Panter Dunsmore
Phone: 434-243-6322
Falls Church
Inova Fairfax Hospital
Status: COMPLETED
Contact: Marshall A. Schorin
Phone: 703-208-6650
Norfolk
Children's Hospital of The King's Daughters
Status: COMPLETED
Contact: Eric Jeffrey Lowe
Phone: 757-668-7243
Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: COMPLETED
Contact: Gita Vasers Massey
Phone: 804-628-1939

Washington

Seattle
Seattle Children's Hospital
Status: COMPLETED
Contact: Douglas S. Hawkins
Phone: 866-987-2000
Spokane
Providence Sacred Heart Medical Center and Children's Hospital
Status: COMPLETED
Contact: Judy L. Felgenhauer
Phone: 800-228-6618
Tacoma
Madigan Army Medical Center
Status: COMPLETED
Contact: Melissa Anne Forouhar
Phone: 253-968-0129
Mary Bridge Children's Hospital and Health Center
Status: COMPLETED
Contact: Robert G. Irwin
Phone: 800-552-1419

Wisconsin

Green Bay
Saint Vincent Hospital Cancer Center Green Bay
Status: COMPLETED
Contact: John Robert Hill
Phone: 920-433-8889
Madison
University of Wisconsin Hospital and Clinics
Status: COMPLETED
Contact: Kenneth Brian De Santes
Phone: 715-422-7718
Marshfield
Marshfield Medical Center-Marshfield
Status: COMPLETED
Contact: Michael John McManus
Phone: 715-389-4457
Milwaukee
Children's Hospital of Wisconsin
Status: COMPLETED
Contact: Michael Edward Kelly
Phone: 414-805-4380

Manitoba

Winnipeg
CancerCare Manitoba
Status: COMPLETED
Contact: Rochelle Avis Yanofsky
Phone: 866-561-1026

Newfoundland and Labrador

Saint John's
Janeway Child Health Centre
Status: COMPLETED
Contact: Lisa Anne Goodyear
Phone: 866-722-1126

Ontario

Hamilton
McMaster Children's Hospital at Hamilton Health Sciences
Status: COMPLETED
Contact: Carol A. Portwine
Phone: 905-521-2100extn74595
Kingston
Kingston Health Sciences Centre
Status: COMPLETED
Contact: Mariana Pradier Silva
Phone: 613-544-2630
Ottawa
Children's Hospital of Eastern Ontario
Status: COMPLETED
Contact: Jacqueline Mary Lewis Halton
Phone: 613-738-3931
Toronto
Hospital for Sick Children
Status: COMPLETED
Contact: Sarah Weeks Alexander
Phone: 416-813-7654extn2027

Quebec

Montreal
Centre Hospitalier Universitaire Sainte-Justine
Status: COMPLETED
Contact: Yvan Samson
Phone: 514-345-4931
The Montreal Children's Hospital of the MUHC
Status: COMPLETED
Contact: Sharon Barbara Abish
Phone: 514-412-4445
Quebec
Centre Hospitalier Universitaire de Quebec
Status: COMPLETED
Contact: Bruno Michon
Phone: 418-525-4444

Saskatchewan

Regina
Allan Blair Cancer Centre
Status: CLOSED_TO_ACCRUAL
Contact: Mansoor Mohammad Haq
Phone: 306-766-2213
Saskatoon
Saskatoon Cancer Centre
Status: COMPLETED
Contact: Christopher Mpofu
Phone: 306-655-2914

Australia

Herston
Royal Children's Hospital-Brisbane
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-823-5923
Hunter Regional Mail Centre
John Hunter Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Elizabeth Louise Hesketh
Parkville
Royal Children's Hospital
Status: COMPLETED
Contact: Francoise Marie Mechinaud
Perth
Princess Margaret Hospital for Children
Status: COMPLETED
Contact: Catherine Helen Cole
Phone: (08) 9340 8222
Randwick
Sydney Children's Hospital
Status: COMPLETED
Contact: Draga Barbaric
Phone: (02) 9382-1721
South Brisbane
Queensland Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Christopher James Fraser
Westmead
The Children's Hospital at Westmead
Status: COMPLETED
Contact: Geoffrey Brian McCowage
Phone: 61-2-9845 1400

PRIMARY OBJECTIVES:

I. For the patients with advanced stage B-cell non-Hodgkin lymphoma (NHL)/Burkitt acute leukemia (B-AL) (stage III and lactate dehydrogenase (LDH) > twice the institutional upper limit of the adult normal values (Nx2), any stage IV or B-AL), to test whether adding 6 injections of rituximab to standard Lymphome Malin B (LMB) chemotherapy regimen, improves the event-free survival (EFS) compared with LMB chemotherapy alone. (Phase III)

II. For patients with primary mediastinal large B-cell lymphoma (PMLBL), to evaluate the EFS following treatment with the regimen dose-adjusted etoposide, prednisone, vincristine sulfate, cyclophosphamide, doxorubicin hydrochloride (DA-EPOCH)-rituximab. (Phase II)

SECONDARY OBJECTIVES:

I. To study the complete remission (CR) rate and the overall survival (OS).

II. To evaluate safety on all study arms including toxic deaths, adverse events recorded using the National Cancer Institute (NCI)-Common Terminology Criteria (CTC) version (V)4 (non hematological toxicity grade >= 3, infections grade 3 to 5), cardiac toxicity (CTC grade 2-5 and evolution of left ventricular ejection fraction and left ventricular shortening fraction), number of days with platelets transfusion, intensive care unit admission and number of days with red cells transfusion, rituximab infusion reactions.

III. To study the rate of patients with immunoglobulin (Ig) (G, A, and M) levels abnormally low and lymphocyte count abnormally low at 1 year and until 5-year follow-up, and to study the need for immunoglobulin infusions, and levels of post (previous and re-) vaccination antibodies at 1 year.

IV. To study long term (at least 5 years) risks of the use of rituximab plus chemotherapy compared with LMB chemotherapy alone in children and adolescents with advanced stage B-NHL/B-AL (all events related [certain and probable] to therapy). (Phase III)

V. To study the long term risk of DA-EPOCH-R regimen, especially the cardiac risk related to doxorubicin given at higher dose than usual in children, but infused over 96 hours (i.e., evaluation of CTC grade 2-5 and evolution of left ventricular ejection fraction and left ventricular shortening fraction). (Phase II)

TERTIARY OBJECTIVES:

I. To obtain data on positron emission tomography (PET)-computed tomography (CT) scan in childhood pediatric B-cell NHL. (Exploratory)

II. To evaluate the potential prognostic value of Minimal Disseminated Disease (MDD) and Minimal Residual disease (MRD) in correlation with outcome. (Exploratory - Phase III)

III. To perform an economic study comparing the cost-effectiveness ratio between 2 therapeutic strategies: LMB chemotherapy with versus LMB chemotherapy without rituximab. (Exploratory - Phase III)

IV. To characterize the pharmacokinetics of rituximab in combination with LMB chemotherapy in a subset of patients. (Exploratory - Phase III)

OUTLINE:

Phase II (patients with PMLBL): Patients receive rituximab intravenously (IV) on day 1; prednisone orally (PO) twice daily (BID) or IV on day on days 1-5; etoposide IV continuously on days 1-4; doxorubicin hydrochloride IV continuously on days 1-4; vincristine sulfate IV continuously on days 1-4; and cyclophosphamide IV on day 5. Patients also receive filgrastim subcutaneously (SC) once daily (QD) beginning on day 6 until blood count recovers. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Phase III:

Group I (pre-phase central nervous system [CNS]-negative, cerebral spinal fluid [CSF]-negative): Patients receive vincristine sulfate IV on day 1; cyclophosphamide IV over 15 minutes on day 1; prednisone PO BID or methylprednisolone IV on days 1-7; methotrexate intrathecally (IT) and hydrocortisone IT on day 1. Patients are randomized to 1 of 2 treatment arms.

Arm I (R-COPADM induction therapy): Beginning 8 days later, patients receive rituximab IV on day 1; vincristine sulfate IV on day 1; prednisone PO BID or methylprednisolone IV on days 1-5; methotrexate IV over 3 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cyclophosphamide IV over 15 minutes on days 2-4; doxorubicin hydrochloride over 1 hour on day 2; and methotrexate IT and hydrocortisone IT on days 2 and 6. Treatment repeats every 18-21 days for 2 courses. Consolidation therapy (R-COPADM): Patients receive rituximab IV on day 1; methotrexate IV over 3 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cytarabine IV continuously on days 2-6; methotrexate IT on day 2; hydrocortisone IT on days 2 and 7; and cytarabine IT on day 7. Treatment repeats every 21 days for 2 courses.

Arm II (COPADM induction therapy): Beginning 8 days later, patients receive vincristine sulfate, prednisone or methylprednisolone, methotrexate, leucovorin calcium, cyclophosphamide, doxorubicin, methotrexate IT, and hydrocortisone IT as in arm I. Treatment repeats every 18-21 days for 2 courses.

Consolidation therapy (COPADM): Patients receive methotrexate IV over 3 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cytarabine IV over 12 hours on days 2-6; methotrexate IT on day 2; hydrocortisone IT on days 2 and 7; and cytarabine IT on day 7. Treatment repeats every 21 days for 2 courses.

Group II (pre-phase B-AL, CNS-negative OR CNS-positive, CSF-negative OR CSF-positive): Patients receive vincristine sulfate IV on day 1; cyclophosphamide IV over 15 minutes on day 1; prednisone PO BID or methylprednisolone IV on days 1-7; methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1, 3, and 5; and leucovorin calcium PO BID on days 2 and 4. Patients are randomized to 1 of 2 treatment arms.

Arm III (R-COPADM induction therapy): Patients receive rituximab IV on days -2 (course 1) and 1; vincristine sulfate IV on day 1; prednisone PO or methylprednisolone IV on days 1-5; high-dose methotrexate IV over 4 hours* on day 1; leucovorin calcium PO every 6 hours on days 2-4; cyclophosphamide IV over 15 minutes on days 2-4; doxorubicin hydrochloride IV on day 2; and methotrexate IT, hydrocortisone IT, and cytarabine IT on days 2, 4, and 6. Treatment repeats every 21 days for 2 courses.

NOTE: *During the second course, patients with CSF-positive disease receive high-dose methotrexate IV over 24 hours (instead of 4 hours).

Consolidation therapy (R-COPADM): Patients receive rituximab IV on day 1; hydrocortisone IT and methotrexate IT on day 1; cytarabine IV over 12 hours on days 1-5; high-dose cytarabine IV over 3 hours on day 2-5; and etoposide IV over 2 hours on days 2-5. If CSF-positive, patients receive high-dose methotrexate IV over 24 hours on day 18, methotrexate IT, hydrocortisone IT, and cytarabine IT on day 19, and leucovorin calcium PO every 6 hours on days 19-21. Treatment repeats every 21 days for 2 courses.

Maintenance therapy (R-COPADM): Patients receive vincristine sulfate IV on day 1; prednisone PO or methylprednisolone IV on days 1-5; high-dose methotrexate IV over 4 hours on day 1; leucovorin calcium PO every 6 hours on days 2-4; cyclophosphamide IV over 15 minutes on days 2-3; doxorubicin hydrochloride over 1 hour on day 2; and methotrexate IT, hydrocortisone IT, and cytarabine IT on day 2. Beginning 28 days later, patients receive cytarabine subcutaneously (SC) every 12 hours on days 1-5 and etoposide IV over 90 minutes on days 1-3.

Arm IV (COPADM induction therapy): Patients receive vincristine sulfate, prednisone or methylprednisolone, high-dose methotrexate*, leucovorin calcium, cyclophosphamide, doxorubicin hydrochloride, and methotrexate, hydrocortisone, and cytarabine IT as in arm III. NOTE: *Patients with CSF-positive disease receive high-dose methotrexate IV over 24 hours (instead of 4 hours).

Consolidation therapy (COPADM): Patients receive hydrocortisone and methotrexate IT, cytarabine, high-dose cytarabine, and etoposide as in arm III consolidation therapy.

Maintenance therapy (COPADM): Patients receive vincristine sulfate, prednisone or methylprednisolone, high-dose methotrexate*, leucovorin calcium, cyclophosphamide, doxorubicin hydrochloride, methotrexate IT, hydrocortisone IT, cytarabine IT, cytarabine SC, and etoposide as in arm III maintenance therapy.

NOTE: *Patients with CSF-positive disease receive high-dose methotrexate IV over 24 hours.

After completion of study treatment, patients are followed up for 5 years.

Trial Phase Phase II/III

Trial Type Treatment

Lead Organization
Children's Oncology Group

Principal Investigator
Thomas Gene Gross

  • Primary ID ANHL1131
  • Secondary IDs NCI-2012-01963, NCT01595048, 2010-019224-31, CDR0000732604, IGR2009/1593, NCT01516567
  • Clinicaltrials.gov ID NCT01516580