A Study of Modified Augmented BFM Therapy for Infants With Acute Lymphoblastic Leukemia
OBJECTIVES:
- Determine the feasibility of dexamethasone-based induction chemotherapy followed by
augmented Berlin-Frankfurt-Munster (BFM) consolidation chemotherapy with or without
allogeneic bone marrow transplantation in infants with previously untreated acute
lymphoblastic leukemia.
- Determine the event-free survival of patients treated with this regimen.
- Determine the clinical prognostic features associated with outcome in these patients.
- Compare the biologic characteristics of the leukemia cells with outcome in these
patients.
OUTLINE: This is a multicenter study.
Patients receive induction therapy comprising oral dexamethasone 3 times daily on days 1-14;
daunorubicin IV on days 1, 8, and 15; vincristine IV on days 1, 8, 15, and 22; and
asparaginase intramuscularly (IM) on days 4, 6, 8, 11, 13, 15, 18, 20, and 22. Patients also
receive methotrexate intrathecally (IT) on days 1, 8, and 15 (and days 4 and 22 for overt
CNS disease).
Patients with M1 or M2 marrow after induction therapy receive augmented consolidation
therapy when blood counts recover. Patients receive cyclophosphamide IV on days 1 and 29;
cytarabine IV or subcutaneously (SC) on days 2-5, 9-12, 30-33, and 37-40; oral
mercaptopurine on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50;
pegaspargase IM on days 15 and 43; and methotrexate IT on days 1, 8, and 15.
Patients who do not receive bone marrow transplantation (BMT) proceed to interim maintenance
#1 when blood counts recover. Patients receive methotrexate IT on days 1, 11, 22, and 32;
methotrexate IV and vincristine IV on days 1, 11, 22, 32, and 43; and pegaspargase IM on
days 2 and 23.
When blood counts recover, patients receive delayed intensification #1 comprising
vincristine IV on days 1, 8, 15, 43, and 50; doxorubicin IV on days 1, 8, and 15; oral
dexamethasone 3 times daily on days 1-7 and 15-21; pegaspargase IM on days 4 and 43;
cyclophosphamide IV on day 29; methotrexate IT on days 29 and 36; oral thioguanine on days
29-42; and cytarabine IV or SC on days 30-33 and 37-40.
When blood counts recover, patients receive interim maintenance #2 comprising vincristine as
in interim maintenance #1; methotrexate IT on day 1 and IV on days 1, 11, 22, 32, and 41;
and pegaspargase IM on days 2 and 23.
When blood counts recover, patients receive delayed intensification #2 comprising
vincristine, doxorubicin, dexamethasone, pegaspargase, cyclophosphamide, cytarabine, and
thioguanine as in intensification #1. Patients also receive methotrexate IT on days 1 and
29.
When blood counts recover, patients receive maintenance therapy comprising methotrexate IT
on day 1 and orally on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; vincristine IV
on days 1, 29, and 57; oral dexamethasone 3 times daily on days 1-5, 29-33, and 57-61; and
oral mercaptopurine daily. Treatment repeats every 84 days for 6 courses.
Patients with an allergy to pegaspargase replace it with asparaginase IM on the days after
receiving methotrexate IV during interim maintenance #1 and #2 and daily over 6 days in
place of each dose of pegaspargase during delayed intensification #1 and #2.
After augmented consolidation therapy, patients meeting the following criteria may receive
BMT in place of chemotherapy:
- In remission
- Exhibiting chromosome translocation involving 11q23 or Ph+{(9;22)}
- Available HLA-A, B, DR genotypic identical relative donor
- No uncontrolled infection
- Adequate organ function Within 3-4 weeks of consolidation therapy, patients undergoing
allogeneic BMT receive cytarabine IV over 1 hour on days -8 to -5; cyclophosphamide IV
over 30 minutes on days -7 and -6; and methylprednisolone IV twice daily on days -2 to
0. Patients also undergo total body irradiation twice daily on days -3 to 0. Patients
receive allogeneic BMT on day 0. Patients also receive cyclosporine IV every 12 hours
beginning on day -1, switching to oral when possible, and continuing until day 60.
Patients then taper cyclosporine over the next 60-120 days.
Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months
for 1 year, every 6 months for 1-2 years, and then annually thereafter.
PROJECTED ACCRUAL: A maximum of 20-40 patients will be accrued for this study within 2
years.
Interventional
Primary Purpose: Treatment
Paul S. Gaynon, MD
Study Chair
Children's Hospital Los Angeles
United States: Federal Government
CDR0000068787
NCT00022126
November 2002
Name | Location |
---|---|
Baylor College of Medicine | Houston, Texas 77030 |
University of Texas - MD Anderson Cancer Center | Houston, Texas 77030-4009 |
University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
Jonsson Comprehensive Cancer Center, UCLA | Los Angeles, California 90095-1781 |
Emory University Hospital - Atlanta | Atlanta, Georgia 30322 |
University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
Indiana University Cancer Center | Indianapolis, Indiana 46202-5265 |
Lineberger Comprehensive Cancer Center, UNC | Chapel Hill, North Carolina 27599-7295 |
Mount Sinai School of Medicine | New York, New York 10029 |
Penn State Cancer Institute at Milton S. Hershey Medical Center | Hershey, Pennsylvania 17033-0850 |
Huntsman Cancer Institute | Salt Lake City, Utah 84112 |
Loma Linda University Medical Center | Loma Linda, California 92354 |
Deaconess Medical Center | Spokane, Washington 99210-0248 |
University of Wisconsin Comprehensive Cancer Center | Madison, Wisconsin 53792 |
Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center | Orange, California 92868 |
Holden Comprehensive Cancer Center at University of Iowa | Iowa City, Iowa 52242-1002 |
CCOP - Columbia River Oncology Program | Portland, Oregon 97225 |
CCOP - Scott and White Hospital | Temple, Texas 76508 |
CCOP - St. Vincent Hospital Cancer Center, Green Bay | Green Bay, Wisconsin 54301 |
MBCCOP - LSU Health Sciences Center | New Orleans, Louisiana 70112 |
Madigan Army Medical Center | Tacoma, Washington 98431-5048 |
Cancer Institute of New Jersey | New Brunswick, New Jersey 08901 |
Children's Hospital Los Angeles | Los Angeles, California 90027-0700 |
Children's Hospital of Orange County | Orange, California 92668 |
Children's Hospital of Denver | Denver, Colorado 80218 |
Children's National Medical Center | Washington, District of Columbia 20010-2970 |
Children's Mercy Hospital | Kansas City, Missouri 64108 |
Children's Hospital of Columbus | Columbus, Ohio 43205-2696 |
Doernbecher Children's Hospital | Portland, Oregon 97201-3098 |
Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
Children's Hospital and Regional Medical Center - Seattle | Seattle, Washington 98105 |
Children's Healthcare of Atlanta - Scottish Rite | Atlanta, Georgia 30342 |
John Stoddard Cancer Center at Iowa Methodist Medical Center | Des Moines, Iowa 50309 |
Phoenix Children's Hospital | Phoenix, Arizona 85016-7710 |
Children's Hospital Central California | Madera, California 93638-8762 |
Children's Hospital of Oakland | Oakland, California 94609-1809 |
University of Connecticut Health Center | Farmington, Connecticut 06360-7106 |
Children's Hospitals and Clinics - Minneapolis | Minneapolis, Minnesota 55404 |
Children's Hospital Medical Center of Akron | Akron, Ohio 44308 |
Children's Medical Center - Dayton | Dayton, Ohio 45404 |
Herbert Irving Comprehensive Cancer Center at Columbia University | New York, New York 10032 |
Cincinnati Children's Hospital Medical Center | Cincinnati, Ohio 45229-3039 |
CCOP - Marshfield Clinic Research Foundation | Marshfield, Wisconsin 54449 |
Alfred I. duPont Hospital for Children | Wilmington, Delaware 19803 |
Children's Hospitals and Clinics - Minnesota | Saint Paul, Minnesota 55102 |
Methodist Cancer Center | San Antonio, Texas 78229-3902 |