Combination Chemotherapy With or Without Donor Bone Marrow Transplantation in Treating Infants With Previously Untreated Acute Lymphoblastic Leukemia
- Conditions
- Leukemia
- Interventions
- Procedure: allogeneic bone marrow transplantationRadiation: radiation therapy
- Registration Number
- NCT00022126
- Lead Sponsor
- Children's Oncology Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Giving the drugs in different combinations may kill more cancer cells. Bone marrow transplantation allows the doctor to give higher doses of chemotherapy and kill more cancer cells.
PURPOSE: Phase II trial to compare the effectiveness of combination chemotherapy with or without donor bone marrow transplantation in treating infants who have previously untreated acute lymphoblastic leukemia.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 6
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Modified Augmented BFM Therapy asparaginase - Modified Augmented BFM Therapy allogeneic bone marrow transplantation - Modified Augmented BFM Therapy daunorubicin hydrochloride - Modified Augmented BFM Therapy vincristine sulfate - Modified Augmented BFM Therapy radiation therapy - Modified Augmented BFM Therapy cyclosporine - Modified Augmented BFM Therapy cytarabine - Modified Augmented BFM Therapy cyclophosphamide - Modified Augmented BFM Therapy doxorubicin hydrochloride - Modified Augmented BFM Therapy dexamethasone - Modified Augmented BFM Therapy mercaptopurine - Modified Augmented BFM Therapy methotrexate - Modified Augmented BFM Therapy methylprednisolone - Modified Augmented BFM Therapy pegaspargase - Modified Augmented BFM Therapy thioguanine -
- Primary Outcome Measures
Name Time Method Establish whether the CCG Augmented Regimen (AR) can be successfully administered in the infant age group
- Secondary Outcome Measures
Name Time Method Grade 3 or 4 non-hematologic toxicity rates Event-free survival
Trial Locations
- Locations (51)
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Emory University Hospital - Atlanta
🇺🇸Atlanta, Georgia, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Lineberger Comprehensive Cancer Center, UNC
🇺🇸Chapel Hill, North Carolina, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Children's Medical Center - Dayton
🇺🇸Dayton, Ohio, United States
Children's Hospitals and Clinics - Minnesota
🇺🇸Saint Paul, Minnesota, United States
Herbert Irving Comprehensive Cancer Center at Columbia University
🇺🇸New York, New York, United States
University of Chicago Cancer Research Center
🇺🇸Chicago, Illinois, United States
Indiana University Cancer Center
🇺🇸Indianapolis, Indiana, United States
Children's Hospital of Columbus
🇺🇸Columbus, Ohio, United States
Children's Hospital and Regional Medical Center - Seattle
🇺🇸Seattle, Washington, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Children's Hospital of Denver
🇺🇸Denver, Colorado, United States
Children's Hospitals and Clinics - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Doernbecher Children's Hospital
🇺🇸Portland, Oregon, United States
CCOP - Columbia River Oncology Program
🇺🇸Portland, Oregon, United States
Methodist Cancer Center
🇺🇸San Antonio, Texas, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Children's Hospital of Oakland
🇺🇸Oakland, California, United States
Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center
🇺🇸Orange, California, United States
University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
MBCCOP - LSU Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Mount Sinai School of Medicine
🇺🇸New York, New York, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
University of Texas - MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
CCOP - Scott and White Hospital
🇺🇸Temple, Texas, United States
University of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Madigan Army Medical Center
🇺🇸Tacoma, Washington, United States
CCOP - St. Vincent Hospital Cancer Center, Green Bay
🇺🇸Green Bay, Wisconsin, United States
Deaconess Medical Center
🇺🇸Spokane, Washington, United States
CCOP - Marshfield Clinic Research Foundation
🇺🇸Marshfield, Wisconsin, United States
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
Women's and Children's Hospital
🇦🇺North Adelaide, South Australia, Australia
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Children's Healthcare of Atlanta - Scottish Rite
🇺🇸Atlanta, Georgia, United States
Jonsson Comprehensive Cancer Center, UCLA
🇺🇸Los Angeles, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
John Stoddard Cancer Center at Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Holden Comprehensive Cancer Center at University of Iowa
🇺🇸Iowa City, Iowa, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada