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Last Modified: 8/29/2008     First Published: 3/24/2003  
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Cetuximab for Advanced Lung Cancer

Past Highlights
Phase II Pilot Study of Rituximab Added to the Induction and Consolidation Phases and Rasburicase Added to the Reduction Phase in Children With Newly Diagnosed Advanced B-Cell Leukemia or Lymphoma Treated With LMB/FAB Therapy

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Rituximab, Rasburicase, and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Advanced B-Cell Leukemia or Lymphoma

Basic Trial Information

Phase
 Type
 Status
 Age
 Sponsor
 Protocol IDs

Phase II
Treatment
Active
1 to 29
NCI
COG-ANHL01P1
NCT00057811, ANHL01P1

Objectives

  1. Determine the toxicity of the addition of rituximab to induction chemotherapy comprising vincristine, methylprednisolone, methotrexate, leucovorin calcium, cyclophosphamide, and doxorubicin (COPADM) [COMRAP] and to consolidation chemotherapy in children with newly diagnosed FAB prognostic group B or group C leukemia or lymphoma treated with LMB/FAB therapy.
  2. Determine the toxicity of the addition of rasburicase to the reduction phase comprising cyclophosphamide, vincristine, prednisone or methylprednisolone, methotrexate, and leucovorin calcium (COP-R) in these patients.
  3. Determine the incidence of tumor lysis syndrome, renal complications, and the use of assisted renal support (i.e., dialysis or hemofiltration) during the COP-R reduction phase and the first induction phase of COPADM or COMRAP in these patients.
  4. Determine the response rate of patients treated with COMRAP incorporated into LMB/FAB therapy.
  5. Assess minimal residual disease in patients before and during COMRAP therapy incorporated into LMB/FAB therapy.

Entry Criteria

Disease Characteristics:

  • Newly diagnosed mature B-lineage (CD20-positive) leukemia or lymphoma by the REAL classification of 1 of the following subtypes:
    • Diffuse large cell lymphoma
    • Burkitt's lymphoma
    • High-grade B-cell lymphoma (Burkitt-like)


  • No B-cell anaplastic large cell Ki-1 positive lymphomas and B-lymphoblastic lymphomas


  • One of the following FAB prognostic groups:
    • Group B (intermediate risk)
    • Group C (high risk)
      • Bone marrow involvement with at least 25% blasts and/or CNS involvement meeting 1 or more of the following criteria:
        • Any L3 blasts in cerebrospinal fluid
        • Cranial nerve palsy (if not explained by extracranial tumor)
        • Clinical spinal cord compression
        • Isolated intracerebral mass
        • Parameningeal extension (cranial and/or spinal)

     [Note: Patients with FAB Group A disease (completely resected stage I and abdominal stage II lesions) are not eligible]



 [Note: *A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.]

Prior/Concurrent Therapy:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • At least 1 week since prior steroids except emergency steroids initiated within 72 hours of study entry

Radiotherapy

  • No prior radiotherapy except emergency radiotherapy initiated within 72 hours of study entry
  • No concurrent radiotherapy

Surgery

  • No prior solid organ transplantation

Patient Characteristics:

Age

  • 1 to 29

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Hepatitis B status known

Renal

  • Not specified

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after study participation
  • No known history of congenital immune deficiency and/or laboratory evidence of acquired immune deficiency
  • No known G6PD deficiency (if receiving rasburicase)
  • No prior malignancies treated with systemic chemotherapy with alkylator or anthracycline therapy

Expected Enrollment

90

A total of 90 patients (50 for group B and 40 for group C) will be accrued for this study within 2.5 years.

Outcomes

Primary Outcome(s)

Toxicity
Incidence of tumor lysis syndrome
Response rate
Minimal residual disease

Outline

This is a multicenter study. Patients are stratified according to FAB prognostic group (B vs C) and treated by group classification.

FAB Group B

  • Treatment I (first 6 patients):
    • Reduction Therapy: Patients receive the COP-R regimen comprising cyclophosphamide IV over 15 minutes, vincristine IV, and methotrexate and hydrocortisone intrathecally (IT) on day 0; rasburicase* IV over 30 minutes every 12 hours on days 0 and 1 and then once daily on days 2-4 (patients exhibiting hyperuricemia and clinical suspicion of B-cell non-Hodgkin's lymphoma or B-cell acute lymphocytic leukemia also receive rasburicase on days -3, -2, and -1); leucovorin calcium IV or orally every 12 hours on days 1 and 3; and prednisone (PRED) or methylprednisolone (MePRDL) IV (or orally) on days 0-6. Patients too critical to proceed may receive another course of reduction therapy.

       [Note: *Patients with G6PD deficiency do not receive rasburicase during reduction therapy.]

    • Induction Therapy: Patients with less than 20% tumor reduction follow the group C induction phase (described below). Patients with at least 20% tumor reduction receive 1 course of the COPADM regimen: vincristine IV and methotrexate IV over 4 hours on day 0; PRED or MePRDL IV (or orally) on days 0-7; leucovorin calcium IV or orally every 6 hours for 12 doses on days 1-3; doxorubicin IV over 30-60 minutes on day 1; cyclophosphamide IV over 15 minutes every 12 hours on days 1-3; methotrexate IT and hydrocortisone IT on days 1 and 5; and filgrastim (G-CSF) subcutaneously (SC) beginning on day 6 and continuing until blood counts recover.

      Patients receive the second part of induction therapy when peripheral blood counts have recovered but no fewer than 16 days after the first part of induction therapy. Patients receive 1 course of the COMRAP regimen comprising rituximab IV on days -2 and 0 with COPADM as in the first part of induction therapy.

    • Consolidation Therapy: Patients receive the CYM-RM regimen comprising rituximab IV and methotrexate IV over 4 hours on day 0; leucovorin calcium IV or orally every 6 hours for 12 doses on days 1-3; cytarabine IV over 24 hours daily on days 1-5; hydrocortisone IT on days 1 and 6; methotrexate IT on day 1; and cytarabine IT on day 6.

      After full recovery from consolidation therapy, patients with any residual masses undergo surgical excision or biopsy. Patients with histology positive for tumor (even if completely resected) proceed to Group C consolidation therapy (described below). Patients with histology negative for tumor proceed to Group B maintenance therapy.

    • Maintenance Therapy: Patients receive the COPADM regimen comprising vincristine IV and methotrexate IV over 4 hours on day 0; PRED or MePRDL IV (or orally) on days 0-7; doxorubicin IV over 30-60 minutes, and cyclophosphamide IV over 30 minutes on days 1 and 2; methotrexate IT and hydrocortisone IT on day 1; and leucovorin calcium IV or orally every 6 hours on days 1-3 (12 doses).


  • Treatment II (44 patients):
    • Reduction Therapy: Patients receive the COP-R regimen as in treatment I.


    • Induction Therapy: Patients receive 2 courses of the COMRAP regimen as in the second induction of treatment I.


    • Consolidation Therapy: Patients receive the CYM-RM regimen as in treatment I.


    • Maintenance Therapy: Patients receive the COPADM regimen as in treatment I.




FAB Group C:

  • Treatment I (first 3 patients):
    • Reduction Therapy: Patients receive the COP-R regimen as in group B treatment I, with the addition of triple intrathecal therapy (TIT) comprising methotrexate, hydrocortisone, and cytarabine on days 0, 2, and 4.


    • Induction Therapy: Patients receive 2 courses of the COPADM regimen as in group B treatment I, with the addition of TIT on days 1, 3, and 5.

      Patients in group C who have biopsy-proven disease after induction therapy are off protocol therapy and treated at the discretion of the investigator.



    • Consolidation Therapy
      • CNS-positive disease: Patients receive 2 courses of the CYVE-RM regimen comprising rituximab IV and methotrexate and hydrocortisone IT on day 0; cytarabine IV over 12 hours on days 0-4; high-dose cytarabine IV over 3 hours and etoposide IV over 2 hours on days 1-4; and G-CSF SC on days 6-20. During the first course, patients also receive HD-MTX IV over 4 hours on day 17; TIT on day 18; and leucovorin calcium IV or orally every 6 hours on days 18-21 (12 doses).
      • CNS-negative disease: Patients receive the CYVE-RM regimen without intrathecal therapy, HD-MTX, or leucovorin calcium.

      After full recovery from consolidation therapy, patients with any residual masses undergo surgical excision or biopsy. Patients who do not achieve complete remission after consolidation therapy are considered treatment failures.



    • Maintenance Therapy (each course lasts 28 days):
      • Course M1: Patients receive vincristine IV and high-dose methotrexate IV over 4 hours on day 0; PRED or MePRDL IV (or orally) on days 0-7; doxorubicin IV over 30-60 minutes and TIT on day 1; cyclophosphamide IV over 30 minutes on days 1 and 2; and leucovorin calcium IV or orally every 6 hours on days 1-4 (12 doses).


      • Course M2: Patients receive etoposide IV over 90 minutes on days 0-2 and cytarabine SC every 12 hours on days 0-4.


      • Course M3: Patients receive vincristine IV on day 0; cyclophosphamide IV over 30 minutes on days 0 and 1; PRED or MePRDL IV (or orally) twice daily on days 0-7; and doxorubicin IV over 30-60 minutes on day 0 (after first dose of cyclophosphamide).


      • Course M4: Patients receive etoposide and cytarabine as in course M2.






  • Treatment II (37 patients):
    • Reduction Therapy: Patients receive 2 courses of the COP-R regimen as in group C treatment I.
    • Induction Therapy: Patients receive the COMRAP regimen comprising rituximab IV, vincristine IV, and HD-MTX IV over 4 hours on day 0; PRED or MePRDL IV (or orally) on days 0-7; leucovorin calcium IV or orally and cyclophosphamide IV over 15 minutes on days 1-3; doxorubicin IV over 30-60 minutes on day 1; TIT on days 1, 3, and 5; and G-CSF SC on days 6-20.
    • Consolidation Therapy
      • CNS-positive disease: Patients receive the CYVE-RM regimen plus HD-MTX as in group C treatment I. Patients then receive CYVE-RM for a second course.
      • CNS-negative disease: Patients receive CYVE-RM regimen as in group C treatment I.
    • Maintenance Therapy: Patients receive maintenance therapy as in group C treatment I.


Patients are followed every 3-6 months for 1 year and then every 6 months thereafter.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Mitchell Cairo, MD, Protocol chair
Ph: 212-305-8316
Email: mc1310@columbia.edu

Trial Sites

U.S.A.
Alabama
  Birmingham
 Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham
 Clinical Trials Office - Lurleen Wallace Comprehensive Cancer
Ph: 205-934-0309
Arizona
  Phoenix
 Phoenix Children's Hospital
 Jessica Boklan
Ph: 602-546-0920
Arkansas
  Little Rock
 Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
 Clinical Trial Office - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Ph: 501-686-8274
California
  Downey
 Southern California Permanente Medical Group
 Robert Cooper
Ph: 323-783-5307
  Loma Linda
 Loma Linda University Cancer Institute at Loma Linda University Medical Center
 Clinical Trials Office - Loma Linda University Cancer Institute
Ph: 909-558-3375
  Long Beach
 Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
 Jerry Finklestein
Ph: 562-492-1062
  Los Angeles
 Childrens Hospital Los Angeles
 Leo Mascarenhas
Ph: 323-361-2529
  Madera
 Children's Hospital Central California
 Vonda Crouse
Ph: 559-353-5480
  Sacramento
 Kaiser Permanente Medical Center - Oakland
 Vincent Kiley
Ph: 916-973-7331
  San Francisco
 UCSF Helen Diller Family Comprehensive Cancer Center
 Clinical Trials Office - UCSF Helen Diller Family Comprehensive Cancer Center
Ph: 877-827-3222
  Stanford
 Stanford Cancer Center
 Clinical Trials Office - Stanford Cancer Center
Ph: 650-498-7061
 Email: cctoffice@stanford.edu
Colorado
  Aurora
 Children's Hospital Center for Cancer and Blood Disorders
 Kelly Maloney
Ph: 720-777-6673
Connecticut
  Farmington
 Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
 Clinical Trials Office - Carole and Ray Neag Comprehensive Cancer Center
Ph: 800-579-7822
Delaware
  Wilmington
 Alfred I. duPont Hospital for Children
 Clinical Trials Office - Alfred I. duPont Hospital for Children
Ph: 302-651-5755
District of Columbia
  Washington
 Children's National Medical Center
 Clinical Trials Office - Children's National Medical Center
Ph: 202-884-2549
 Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
 Clinical Trials Office - Lombardi Comprehensive Cancer Center
Ph: 202-444-0381
Florida
  Fort Myers
 Lee Cancer Care of Lee Memorial Health System
 Clinical Trials Office - Lee Cancer Care of Lee Memorial Health System
Ph: 877-680-0008
  Jacksonville
 Nemours Children's Clinic
 Eric Sandler
Ph: 904-390-3793
  Miami
 Baptist-South Miami Regional Cancer Program
 Doured Daghistani
Ph: 305-274-1662
 University of Miami Sylvester Comprehensive Cancer Center - Miami
 University of Miami Sylvester Comprehensive Cancer Center Clinical Trial Matching Service
Ph: 866-574-5124
 Email: Sylvester@emergingmed.com
  Orlando
 Florida Hospital Cancer Institute at Florida Hospital Orlando
 Clinical Trials Office - Florida Hospital Cancer Institute
Ph: 407-303-5623
  Pensacola
 Sacred Heart Cancer Center at Sacred Heart Hospital
 Clinical Trials Office - Sacred Heart Cancer Center
Ph: 850-416-4611
  St. Petersburg
 All Children's Hospital
 Jerry Barbosa
Ph: 727-767-4176
  Tampa
 St. Joseph's Cancer Institute at St. Joseph's Hospital
 Clinical Trials Office - St. Joseph's Cancer Institute
Ph: 800-882-4123
  West Palm Beach
 Kaplan Cancer Center at St. Mary's Medical Center
 Narayana Gowda
Ph: 561-844-6363
Georgia
  Atlanta
 Winship Cancer Institute of Emory University
 Howard Katzenstein
Ph: 404-785-0853
  Augusta
 MBCCOP - Medical College of Georgia Cancer Center
 Colleen McDonough
Ph: 706-721-3626
  Savannah
 Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
 Clinical Trials Office - Curtis and Elizabeth Anderson Cancer Institute
Ph: 912-350-8568
Hawaii
  Honolulu
 Cancer Research Center of Hawaii
 Clinical Trials Office - Cancer Research Center of Hawaii
Ph: 808-586-2979
Idaho
  Boise
 Mountain States Tumor Institute at St. Luke's Regional Medical Center
 Eugenia Chang
Ph: 208-381-2731
Indiana
  Indianapolis
 Indiana University Melvin and Bren Simon Cancer Center
 Clinical Trials Office - Indiana University Cancer Center
Ph: 317-274-2552
 St. Vincent Indianapolis Hospital
 Clinical Trials Office - St. Vincent Indianapolis Hospital
Ph: 317-338-2194
Kansas
  Kansas City
 Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
 Clinical Trials Office - Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Ph: 913-588-4709
Kentucky
  Lexington
 Lucille P. Markey Cancer Center at University of Kentucky
 Clinical Trials Office - Markey Cancer Center at University of Kentucky Chandler Medical Center
Ph: 859-257-3379
  Louisville
 Kosair Children's Hospital
 Clinical Trials Office - Kosair Children's Hospital
Ph: 502-629-5500
 Email: CancerResource@nortonhealthcare.org
Maine
  Bangor
 CancerCare of Maine at Eastern Maine Medical Center
 Clinical Trials Office - CancerCare of Maine
Ph: 207-973-4274
Maryland
  Baltimore
 Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
 Joseph Wiley
Ph: 410-601-5864
Michigan
  Ann Arbor
 C.S. Mott Children's Hospital at University of Michigan Medical Center
 Clinical Trials Office - C.S. Mott Children's Hospital
Ph: 1-800-865-1125
  Detroit
 Barbara Ann Karmanos Cancer Institute
 Clinical Trials Office - Barbara Ann Karmanos Cancer Institute
Ph: 313-576-9363
  Flint
 Hurley Medical Center
 Clinical Trials Office - Hurley Medical Center
Ph: 810-762-8057
  Grand Rapids
 Butterworth Hospital at Spectrum Health
 David Dickens
Ph: 616-391-2086
  Grosse Pointe Woods
 Van Elslander Cancer Center at St. John Hospital and Medical Center
 Clincial Trials Office - Van Elslander Cancer Center at St. John Hospital and Medical Center
Ph: 313-343-3166
  Kalamazoo
 CCOP - Kalamazoo
 Leonard Mattano, Jr.
Ph: 269-341-6350
  Lansing
 Breslin Cancer Center at Ingham Regional Medical Center
 Clinical Trials Office - Breslin Cancer Center at Ingham Regional Medical Center
Ph: 517-334-2765
Minnesota
  Minneapolis
 Children's Hospitals and Clinics of Minnesota - Minneapolis
 Clinical Trials Office - Children's Hospitals and Clinics of Minnesota
Ph: 612-813-5193
 Masonic Cancer Center at University of Minnesota
 Clinical Trials Office - Masonic Cancer Center at University of Minnesota
Ph: 612-624-2620
  Rochester
 Mayo Clinic Cancer Center
 Clinical Trials Office - All Mayo Clinic Locations
Ph: 507-538-7623
Mississippi
  Jackson
 University of Mississippi Cancer Clinic
 Gail Megason
Ph: 601-984-5220
Missouri
  Kansas City
 Children's Mercy Hospital
 Maxine Hetherington
Ph: 816-234-3265
  St. Louis
 Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
 Robert Hayashi
Ph: 314-454-4118
Nebraska
  Omaha
 Children's Hospital
 Minnie Abromowitch
Ph: 402-955-3950
Nevada
  Las Vegas
 CCOP - Nevada Cancer Research Foundation
 Jonathan Bernstein
Ph: 702-732-1493
New Hampshire
  Lebanon
 Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
 Clinical Trials Office - Norris Cotton Cancer Center
Ph: 603-650-7609
 Email: cancerhelp@dartmouth.edu
New Jersey
  Hackensack
 Hackensack University Medical Center Cancer Center
 Clinical Trials Office - Hackensack University Medical Center Cancer Center
Ph: 201-996-2879
  New Brunswick
 Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
 Clinical Trials Office - Cancer Institute of New Jersey
Ph: 732-235-8675
  Paterson
 St. Joseph's Hospital and Medical Center
 Mary Ann Bonilla
Ph: 973-754-3349
New Mexico
  Albuquerque
 University of New Mexico Cancer Center
 Clinical Trials Office - University of New Mexico Cancer Center
Ph: 505-272-6972
New York
  Bronx
 Albert Einstein Cancer Center at Albert Einstein College of Medicine
 Clinical Trials Office - Albert Einstein Cancer Center at Albert Einstein College of Medicine
Ph: 718-904-2730
 Email: aecc@aecom.yu.edu
  Brooklyn
 Brooklyn Hospital Center
 Swayamprabha Sadanandan
Ph: 718-250-6074
  Mineola
 Winthrop University Hospital
 Mark Weinblatt
Ph: 516-663-9400
  New York
 Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
 Clinical Trials Office - Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
Ph: 212-305-8615
 NYU Cancer Institute at New York University Medical Center
 Elizabeth Raetz
Ph: 212-263-8400
  Rochester
 James P. Wilmot Cancer Center at University of Rochester Medical Center
 Barbara Asselin
Ph: 585-275-2981
  Syracuse
 SUNY Upstate Medical University Hospital
 Clinical Trials Office - SUNY Upstate Medical University Hospital
Ph: 315-464-5476
  Valhalla
 New York Medical College
 Fevzi Ozkaynak
Ph: 914-493-7997
North Carolina
  Charlotte
 Blumenthal Cancer Center at Carolinas Medical Center
 Clinical Trials Office - Blumenthal Cancer Center at Carolinas Medical Center
Ph: 704-355-2884
 Presbyterian Cancer Center at Presbyterian Hospital
 Clinical Trials Office - Presbyterian Cancer Center at Presbyterian Hospital
Ph: 704-384-5369
Ohio
  Akron
 Akron Children's Hospital
 Clinical Trials Office - Akron Children's Hospital
Ph: 330-543-3193
  Cincinnati
 Cincinnati Children's Hospital Medical Center
 Clinical Trials Office - Cincinnati Children's Hospital Medical Center
Ph: 513-636-0161
  Cleveland
 Rainbow Babies and Children's Hospital
 Susan Wiersma
Ph: 216-844-3345
  Columbus