Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia
RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective for acute lymphoblastic leukemia.
PURPOSE: Phase III trial to determine the effectiveness of combination chemotherapy in treating children who have newly diagnosed acute lymphoblastic leukemia.
Drug: daunorubicin hydrochloride
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||ALinC 17: Protocol for Patients With Newly Diagnosed High Risk Acute Lymphoblastic Leukemia (ALL) - Evaluation of the Augmented BFM Regimen: A Phase III Study|
- Augmented Berlin Frankfurt Muenster (BFM) therapy is superior to ALinC 14/15 therapy [ Designated as safety issue: Yes ]To determine for patients at high risk for treatment failure if the augmented Berlin Frankfurt Muenster (BFM) therapy is superior to ALinC 14/15 therapy, on the basis of historical controls.
|Study Start Date:||March 2000|
|Primary Completion Date:||September 2005 (Final data collection date for primary outcome measure)|
- Determine whether augmented BFM therapy is superior to ALinc 14/15 therapy in patients with newly diagnosed high-risk acute lymphoblastic leukemia.
- Determine whether minimal residual disease after induction therapy is predictive of an inferior prognosis in this patient population.
- Determine the correlation between event-free survival, minimal residual disease, and early response in this patient population treated with this multiple drug regimen.
OUTLINE: Patients are stratified by CNS or testicular disease (yes vs no).
- Induction therapy (weeks 1-5): Patients receive oral prednisone 3 times daily on days 1-29; vincristine IV on days 1, 8, 15, and 22; daunorubicin IV on days 8, 15, 22; and asparaginase intramuscularly (IM) on days 2, 5, 8, 12, 15, and 19. Patients also receive methotrexate intrathecally (IT) on days 1 and 8. Patients with CNS 2 or 3 disease also receive methotrexate IT on days 15 and 22.
Patients with M1 bone marrow proceed to consolidation therapy. Patients achieving M2 bone marrow on day 29 receive oral prednisone 3 times daily on days 29-42; vincristine IV and daunorubicin IV over 15 minutes on days 29 and 36; and asparaginase IM on days 29, 32, 36, and 39. If bone marrow is M3 on day 29 or M2 on day 43, then patient is off study.
- Consolidation therapy (weeks 6-14): Patients receive cyclophosphamide IV over 30 minutes on days 1 and 29; cytarabine subcutaneously (SC) or IV on days 2-5, 9-12, 30-33, and 37-40; oral mercaptopurine daily on days 1-14 and 29-42; vincristine IV on days 15, 22, 43, and 50; asparaginase IM on days 15, 17, 19, 22, 24, 26, 43, 45, 47, 50, 52, and 54; and methotrexate IT on days 1, 15, 29, and 43.
Patients then proceed to interim maintenance and delayed intensification on weeks 15-46. Courses repeat every 16 weeks.
- Maintenance I and II (weeks 15-22 and 31-38): Patients receive vincristine IV and methotrexate IV on days 1, 11, 21, 31, and 41; asparaginase IM on days 2, 12, 22, 32, and 42; and methotrexate IT on days 1 and 31.
- Delayed Intensification (weeks 23-36 and 39-42): Patients receive vincristine IV on days 57, 64, and 71; methotrexate IT on day 57; oral dexamethasone 2-3 times daily on days 57-63 and 71-77; doxorubicin IV over 15 minutes 3 times weekly on days 57, 64, and 71; and asparaginase IM on days 60, 62, 64, 67, 69, and 71.
- Delayed Intensification-Reconsolidation (weeks 27-30 and 43-46): Patients receive oral thioguanine on days 85-98; methotrexate IT on day 85; cyclophosphamide IV over 30 minutes on day 85; cytarabine IV or SC on days 86-89 and 93-96; asparaginase IM on days 99, 101, 103, 106, 108, and 110; and vincristine IV on days 99 and 106.
- Continuation therapy (weeks 47-130): Patients receive vincristine IV on days 1, 29, and 57; oral dexamethasone twice daily for 5 consecutive days on days 1-5, 29-33, and 57-61; oral mercaptopurine on days 1-84; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; and methotrexate IT on day 1.
Patients with CNS 3 disease or who are within 24 months of diagnosis with an initial WBC ≥ 100,000/mm^3 undergo whole brain radiotherapy (omit or discontinue mercaptopurine and IT methotrexate) on day 1. Testicular radiotherapy also begins on day 1.
Patients may receive oral methotrexate on day 1 of each course (if IT methotrexate is not administered).
Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study within 3.1 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005603
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027-0700|
|Lucile Packard Children's Hospital at Stanford|
|Palo Alto, California, United States, 94304|
|UCSF Comprehensive Cancer Center|
|San Francisco, California, United States, 94143-0128|
|United States, District of Columbia|
|Children's National Medical Center|
|Washington, District of Columbia, United States, 20010-2970|
|United States, Illinois|
|Saint Jude Midwest Affiliate|
|Peoria, Illinois, United States, 61637|
|United States, Indiana|
|Indiana University Cancer Center|
|Indianapolis, Indiana, United States, 46202-5289|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Minnesota|
|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, New York|
|Albert Einstein Clinical Cancer Center|
|Bronx, New York, United States, 10461|
|Herbert Irving Comprehensive Cancer Center|
|New York, New York, United States, 10032|
|State University of New York - Upstate Medical University|
|Syracuse, New York, United States, 13210|
|United States, Ohio|
|Children's Hospital Medical Center - Cincinnati|
|Cincinnati, Ohio, United States, 45229-3039|
|United States, Oregon|
|Doernbecher Children's Hospital|
|Portland, Oregon, United States, 97201-3098|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|Children's Hospital of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Texas|
|University of Texas Medical Branch|
|Galveston, Texas, United States, 77555-0361|
|Baylor College of Medicine|
|Houston, Texas, United States, 77030|
|University of Texas - MD Anderson Cancer Center|
|Houston, Texas, United States, 77030-4009|
|United States, Washington|
|Children's Hospital and Regional Medical Center - Seattle|
|Seattle, Washington, United States, 98105|
|Study Chair:||William P. Bowman, MD||Cook Children's Medical Center - Fort Worth|