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Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia
This study has been completed.
First Received: April 7, 2003   Last Updated: February 6, 2009   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00058461
  Purpose

RATIONALE: Chemotherapy drugs, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining ifosfamide, carboplatin, and etoposide with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well rituximab together with ifosfamide, carboplatin, and etoposide works in treating young patients with recurrent or refractory non-Hodgkin's lymphoma or acute lymphoblastic leukemia.


Condition Intervention Phase
Leukemia
Lymphoma
Biological: filgrastim
Biological: rituximab
Drug: carboplatin
Drug: cytarabine
Drug: etoposide
Drug: ifosfamide
Drug: methotrexate
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Study Of Rituximab And ICE Chemotherapy In Children With Recurrent/Refractory B-Cell (CD20+) Non-Hodgkin Lymphoma And B-Cell Acute Lymphoblastic Leukemia

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response [ Designated as safety issue: No ]
  • Relapse-free survival rate [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Mobilization [ Designated as safety issue: No ]
  • Time course of engraftment [ Designated as safety issue: No ]

Study Start Date: November 2003
Detailed Description:

OBJECTIVES:

  • Determine the response of pediatric patients with relapsed or refractory B-cell non-Hodgkin's lymphoma or acute lymphoblastic leukemia treated with ifosfamide, carboplatin, and etoposide combined with rituximab.
  • Determine the relapse-free survival rate of patients treated with this regimen.
  • Determine the toxicity profile of this regimen in these patients, specifically the frequency of therapy delays between courses due to prolonged grade IV hematologic toxicity.
  • Determine whether this regimen plus filgrastim (G-CSF) will result in mobilization of greater than 2 X 10^6/kg peripheral blood stem cells (CD34+ cells, PBSC) in at least 80% of patients for whom peripheral stem cell collection is performed.
  • Determine the time course of engraftment for patients who undergo peripheral stem cell transplantation after collection of stem cells using this mobilization regimen.

OUTLINE: This is a multicenter study. Patients are stratified by disease (B-cell large cell lymphoma or atypical precursor B-cell lmphoblastic lymphoma vs small non-cleaved cell lymphoma or B-cell acute lymphoblastic leukemia).

Patients receive ifosfamide IV over 2 hours and etoposide IV over 1 hour on days 3-5, rituximab IV on days 1 and 3, and carboplatin IV over 1 hour on day 3. Patients receive filgrastim (G-CSF) subcutaneously once daily beginning on day 6 and continuing until blood counts recover.

Patients also receive intrathecal (IT) chemotherapy comprising methotrexate and cytarabine. Patients with B-cell large cell lymphoma and negative CSF cytology receive IT chemotherapy on day 3 of the first course only. Patients with small non-cleaved cell lymphoma or B-cell acute lymphoblastic leukemia and negative CSF cytology receive IT chemotherapy on day 3. All patients with positive CSF cytology receive IT chemotherapy on days 3, 10, and 17 of the first and second courses. Treatment repeats every 23 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 42-82 patients (21-41 per disease stratum) will be accrued for this study within 2-4 years.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed B-cell non-Hodgkin's lymphoma OR acute lymphoblastic leukemia

    • CD20+ (confirmed by flow cytometry of tumor tissue, involved marrow, or CD20 immunostaining)
    • The following histologies are generally CD20+ and are eligible:

      • Diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, or follicular lymphoma, grade III (rare), documented by flow cytometry or appropriate immunohistochemistry, any stage
      • Burkitt's lymphoma or atypical Burkitt's/Burkitt-like lymphoma, any stage
      • B-cell acute lymphoblastic leukemia, with FABL3 morphology and/or demonstration of surface immunoglobin by flow cytometry
      • Atypical precursor B-cell lymphoblastic lymphoma or other unusual histologies that are CD20+
  • Measurable disease by clinical, radiographic, or histologic criteria
  • Must be in first or later recurrence or have disease that is primarily refractory to conventional therapy
  • No isolated CNS disease

PATIENT CHARACTERISTICS:

Age

  • 21 or under when diagnosed with recurrent or refractory disease

Performance status

  • ECOG 0-2

Life expectancy

  • At least 2 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,000/mm^3*
  • Platelet count ≥ 100,000/mm^3 (transfusion independent)*
  • Hemoglobin ≥ 10.0 g/dL (RBC transfusion allowed)* NOTE: *Patients with B-cell acute lymphoblastic leukemia and lymphoma involving bone marrow who have granulocytopenia, anemia, and/or thrombocytopenia are eligible but are not evaluable for hematologic toxicity

Hepatic

  • Bilirubin ≤ 1.5 times normal
  • ALT < 2.5 times normal

Renal

  • No chronic renal insufficiency

    • Renal insufficiency allowed provided it is secondary to tumor lysis syndrome

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after study treatment
  • HIV negative
  • No active uncontrolled infection
  • Seizure disorder allowed if well controlled with anticonvulsants
  • No CNS toxicity greater than grade II

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • At least 24 hours since prior growth factor(s)
  • At least 60 days since prior biologic (antineoplastic) therapy
  • Prior stem cell transplantation allowed provided the following criteria are met:

    • More than 60 days since transplantation
    • Hematopoietic lab value requirements are met (See Hematopoietic)
    • No evidence of graft-versus-host disease (if post-allogeneic transplantation)
  • Prior monoclonal antibody therapy allowed (including rituximab)
  • No other concurrent immunomodulating agents

Chemotherapy

  • More than 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas)
  • No other concurrent chemotherapy

Endocrine therapy

  • No concurrent steroids (except for rituximab infusion-related symptoms)

Radiotherapy

  • At least 2 weeks since prior local palliative radiotherapy (small port)
  • At least 6 weeks since prior substantial bone marrow radiotherapy
  • At least 6 months since prior craniospinal radiotherapy or radiotherapy to 50% or more of the pelvis
  • Concurrent radiotherapy to localized painful, airway-compromising, or other acute organ-threatening lesions allowed provided at least 1 measurable lesion is not irradiated

Surgery

  • Not specified

Other

  • Recovered from prior therapy
  • No concurrent participation in another phase II study
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00058461

  Hide Study Locations
Locations
United States, Alabama
Comprehensive Cancer Center at University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016-7710
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Children's Hospital and Health Center - San Diego
San Diego, California, United States, 92123-4282
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Kaiser Permanente Medical Center - Oakland
Sacramento, California, United States, 95825
Children's Hospital Central California
Madera, California, United States, 93638-8762
Southern California Permanente Medical Group
Downey, California, United States, 90242-2814
Stanford Cancer Center at Stanford University Medical Center
Stanford, California, United States, 94305
United States, Connecticut
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
Farmington, Connecticut, United States, 06360-2875
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19899
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010-2970
United States, Florida
All Children's Hospital
St. Petersburg, Florida, United States, 33701
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, United States, 32803-1273
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States, 33407
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, United States, 33901
Miami Children's Hospital
Miami, Florida, United States, 33155
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
Sacred Heart Cancer Center at Sacred Heart Hospital
Pensacola, Florida, United States, 32504
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States, 33607
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
United States, Georgia
Emory University Hospital - Atlanta
Atlanta, Georgia, United States, 30322
MBCCOP-Medical College of Georgia Cancer Center
Augusta, Georgia, United States, 30912-3730
United States, Hawaii
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States, 95813
United States, Idaho
St. Luke's Mountain States Tumor Institute - Boise
Boise, Idaho, United States, 83712-6297
United States, Illinois
Saint Jude Midwest Affiliate
Peoria, Illinois, United States, 61637
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62794-9620
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
St. Vincent Indianapolis Hospital
Indianapolis, Indiana, United States, 46260
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1083
United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
United States, Kentucky
Kosair Children's Hospital
Louisville, Kentucky, United States, 40232
Markey Cancer Center at University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536-0293
United States, Louisiana
Ochsner Cancer Institute at Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
Tulane Cancer Center
Alexandria, Louisiana, United States, 71315-3198
United States, Maine
CancerCare of Maine at Eastern Maine Medial Center
Bangor, Maine, United States, 04401
Maine Children's Cancer Program
Scarborough, Maine, United States, 04074-9308
United States, Maryland
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States, 21215
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Breslin Cancer Center at Ingham Regional Medical Center
Lansing, Michigan, United States, 48910
C.S. Mott Children's Hospital at University of Michigan
Ann Arbor, Michigan, United States, 48109-0238
Hurley Medical Center
Flint, Michigan, United States, 48503
Spectrum Health Cancer Care - Butterworth Campus
Grand Rapids, Michigan, United States, 49503-2560
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States, 48236
United States, Minnesota
Children's Hospital of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
Fairview University Medical Center - University Campus
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Siteman Cancer Center at Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, Nevada
Sunrise Hospital and Medical Center
Las Vegas, Nevada, United States, 89109-2306
United States, New Jersey
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
Newark Beth Israel Medical Center
Newark, New Jersey, United States, 07112
St. Barnabas Medical Center
Livingston, New Jersey, United States, 07039
United States, New Mexico
University of New Mexico Cancer Research and Treatment Center
Albuquerque, New Mexico, United States, 87131-5636
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Brooklyn Hospital Center
Brooklyn, New York, United States, 11201-5493
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
New York Medical College
Valhalla, New York, United States, 10595
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
Schneider Children's Hospital
New Hyde Park, New York, United States, 11040
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
Winthrop University Hospital
Mineola, New York, United States, 11501
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233-3549
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308-1062
Children's Medical Center - Dayton
Dayton, Ohio, United States, 45404-1815
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195-5217
Columbus Children's Hospital
Columbus, Ohio, United States, 43205-2696
Medical College of Ohio Cancer Institute
Toledo, Ohio, United States, 43614
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106-5000
Tod Children's Hospital - Forum Health
Youngstown, Ohio, United States, 44501
Toledo Hospital
Toledo, Ohio, United States, 43606
United States, Oklahoma
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Institute of Oncology at Vilnius University
Portland, Oregon, United States, 97227
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-9786
Geisinger Medical Center
Danville, Pennsylvania, United States, 17822-0001
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
United States, Rhode Island
Comprehensive Cancer Center at Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, South Carolina
Greenville Hospital System Cancer Center
Greenville, South Carolina, United States, 29605
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, South Dakota
Sioux Valley Hospital and University of South Dakota Medical Center
Sioux Falls, South Dakota, United States, 57117-5039
United States, Tennessee
East Tennessee Children's Hospital
Knoxville, Tennessee, United States, 37916
East Tennessee State University Cancer Center at Johnson City Medical Center
Johnson City, Tennessee, United States, 37604
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6310
United States, Texas
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
Children's Hospital of Austin
Austin, Texas, United States, 78701
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229-3993
Covenant Children's Hospital
Lubbock, Texas, United States, 79410
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104-9958
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Texas Tech University Health Sciences Center School of Medicine
Amarillo, Texas, United States, 79106
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113-1100
United States, Virginia
Massey Cancer Center at Virginia Commonwealth University
Richmond, Virginia, United States, 23298-0037
Children's Hospital of the King's Daughters
Norfolk, Virginia, United States, 23507-1971
INOVA Fairfax Hospital
Fairfax, Virginia, United States, 22031
Carilion Cancer Center of Western Virginia
Roanoke, Virginia, United States, 24029
United States, Washington
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States, 98105
Madigan Army Medical Center - Tacoma
Tacoma, Washington, United States, 98431
United States, West Virginia
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
Charleston, West Virginia, United States, 25302
United States, Wisconsin
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States, 54307-3508
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Australia, New South Wales
Prince of Wales Private Hospital
Randwick, New South Wales, Australia, 2031
Australia, Queensland
Royal Children's Hospital
Herston, Brisbane, Queensland, Australia, 4029
Australia, South Australia
Women's and Children's Hospital
North Adelaide, South Australia, Australia, 5006
Australia, Western Australia
Princess Margaret Hospital for Children
Perth, Western Australia, Australia, 6001
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T2T 5C7
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Children's & Women's Hospital of British Columbia
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3K 6R8
Canada, Ontario
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 3N6
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Canada, Quebec
Centre Hospitalier Universitaire de Quebec
Ste-Foy, Quebec, Canada, G1V 4G2
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada, H3H 1P3
Canada, Saskatchewan
Allan Blair Cancer Centre at Pasqua Hospital
Regina, Saskatchewan, Canada, S4T 7T1
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Timothy C. Griffin, MD Cook Children's Medical Center - Fort Worth
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000298751, COG-ANHL0121
Study First Received: April 7, 2003
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00058461     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute lymphoblastic leukemia
recurrent childhood large cell lymphoma
B-cell childhood acute lymphoblastic leukemia
childhood diffuse large cell lymphoma
recurrent childhood small noncleaved cell lymphoma
childhood immunoblastic large cell lymphoma
L3 childhood acute lymphoblastic leukemia
recurrent childhood lymphoblastic lymphoma
Burkitt lymphoma

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Leukemia, Lymphoid
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Tumor Virus Infections
Reproductive Control Agents
Neoplasms, Experimental
Lymphoma, B-Cell
Leukemia
Therapeutic Uses
Abortifacient Agents
Methotrexate
Epstein-Barr Virus Infections
Dermatologic Agents
Alkylating Agents
Lymphoma
Etoposide
Nucleic Acid Synthesis Inhibitors
Cytarabine
Neoplasms by Histologic Type
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Enzyme Inhibitors
Carboplatin

ClinicalTrials.gov processed this record on November 27, 2009