Combination Chemotherapy in Treating Children With Very High Risk Acute Lymphocytic Leukemia
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug and combining drugs in different ways may kill more cancer cells.
PURPOSE: Phase II trial to study the effectiveness of chemotherapy in treating children who have very high risk acute lymphocytic leukemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
OBJECTIVES: I. Determine the feasibility of administering a new combination of agents during postinduction consolidation therapy in children with very high risk acute lymphocytic leukemia (VHR-ALL). II. Assess the tolerance of patients in remission of VHR-ALL for postconsolidation therapy with continuous intensification.
OUTLINE: Patients receive induction therapy on weeks 1-4. This consists of oral prednisone three times a day on days 1-28; vincristine IV on days 1, 8, 15, and 22; daunorubicin IV on days 8, 15, and 22; and asparaginase 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 and 3 disease also receive methotrexate IT on days 15 and 22. Patients who achieve M2 bone marrow on day 29 receive oral prednisone three times a day 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 or M3 on day 43, then patient is off study. Patients proceed to consolidation therapy on weeks 5-25. This consists of high dose methotrexate IV over 24 hours on weeks 6, 8, 16, and 18, followed by leucovorin calcium IV or orally every 6 hours for 5 doses; oral mercaptopurine on weeks 6-9 and 16-19; cytarabine IV over 6 hours followed by idarubicin IV over 15 minutes for 4 days; and filgrastim (G-CSF) subcutaneously (SQ) beginning on day 5 and continuing for about 10-14 days on weeks 10 and 20. Patients receive etoposide IV over 1 hour followed by cyclophosphamide IV over 10 minutes for 5 days and G-CSF SQ beginning on day 6 for 10-14 days on weeks 13 and 23. Methotrexate IT is administered on weeks 6, 8, 13, 16, 18, and 23. Patients then proceed to continuous intensification therapy during weeks 26-61. Patients receive vincristine IV, daunorubicin IV, and methotrexate IT on day 1, and oral dexamethasone twice a day on days 1-7 on weeks 26, 32, 38, 44, 50, and 56. Patients also receive high dose cytarabine IV over 1 hour, every 12 hours, for 4 doses, followed by asparaginase IM 3 hours after the last dose of cytarabine, on weeks 27, 33, 39, 45, 51, and 57. Oral mercaptopurine and methotrexate IM are administered on day 1 during weeks 29, 31, 35, 37, 41, 43, 47, 49, 53, 55, 59, and 61. Patients receive etoposide IV over 1-2 hours followed by cyclophosphamide IV during weeks 30, 36, 42, 48, 54, and 60. Patients then proceed to continuation therapy during weeks 62-126. Vincristine IV and cyclophosphamide IV are administered on weeks 62-65, 70-73, 78-81, 86-89, 94-97, 102-105, 110-113, and 118-121. Patients also receive oral dexamethasone twice a day for 7 days on weeks 62, 70, 78, 86, 94, 102, 110, and 118, and cytarabine IV on weeks 63, 65, 71, 73, 79, 81, 87, 89, 95, 97, 103, 105, 111, 113, 119, and 121. Oral mercaptopurine is administered daily during weeks 66-69, 74-77, 82-85, 90-93, 98-101, 106-109, 114-117, and 122-125 and methotrexate IM on weeks 66-69, 74-77, 82-85, 90-93, 98-101, 106-109, 114-117, and 122-125. Methotrexate IT is administered during weeks 62, 70, 78, 86, 94, 102, 110, and 118. Patients who are CNS 3 at diagnosis receive whole brain irradiation beginning at week 62 along with the first course of continuation therapy. These patients do not receive any methotrexate IT after week 62. Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, then annually thereafter.
PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study within 12 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Complete Response and no CNS 3 See detailed description. |
Biological: filgrastim
Other Names:
Drug: asparaginase
Other Names:
Drug: cyclophosphamide
Other Names:
Drug: cytarabine
Other Names:
Drug: daunorubicin hydrochloride
Other Names:
Drug: dexamethasone
Other Names:
Drug: etoposide
Other Names:
Drug: idarubicin
Other Names:
Drug: leucovorin calcium
Other Names:
Drug: mercaptopurine
Other Names:
Drug: methotrexate
Other Names:
Drug: prednisone
Other Names:
Drug: vincristine sulfate
Other Names:
Radiation: radiation therapy
|
| Experimental: Complete Response and CNS 3 See detailed description. |
Biological: filgrastim
Other Names:
Drug: asparaginase
Other Names:
Drug: cyclophosphamide
Other Names:
Drug: cytarabine
Other Names:
Drug: daunorubicin hydrochloride
Other Names:
Drug: dexamethasone
Other Names:
Drug: etoposide
Other Names:
Drug: idarubicin
Other Names:
Drug: leucovorin calcium
Other Names:
Drug: mercaptopurine
Other Names:
Drug: methotrexate
Other Names:
Drug: prednisone
Other Names:
Drug: vincristine sulfate
Other Names:
Radiation: radiation therapy
|
Outcome Measures
Primary Outcome Measures
- Assess the feasibility of delivering a new combination of agents during a 20 week post-induction consolidation phase [20 weeks]
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS: Newly diagnosed B-cell precursor acute lymphocytic leukemia No L3 morphology Very poor prognosis CNS 3 (blasts and WBC greater than 5 microliters) OR Must meet all of the following criteria: No simultaneous trisomy 4 and 10 DNA index no greater than 1.16 (if FISH 4 and 10 unsatisfactory) No TEL-AML1 [t(12;21)] Meets at least 1 of the following: Has MLL (11q23) and/or BCR-ABL [t(9;22)] WBC greater than 100,000/mm3 Age over 12 (boys) or 16 (girls) OR Boys Girls WBC 8 12 greater than 80,000/mm3 9 13 greater than 60,000/mm3 10 14 greater than 40,000/mm3 11 15 greater than 20,000/mm3 Concurrent registration on stratum 6 of POG-9400 before 11/15/1999 OR Concurrent registration on stratum 4 of POG-9900 after 11/15/1999 Concurrent registration on POG-9201, POG-9705, or POG-9806 unless ineligible
PATIENT CHARACTERISTICS: Age: Children Performance status: Not specified Life expectancy:
Not specified Hematopoietic: See Disease Characteristics Hepatic: Not specified Renal: Not specified
PRIOR CONCURRENT THERAPY: See Disease Characteristics
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Arizona Cancer Center | Tucson | Arizona | United States | 85724 |
| 2 | Lucile Packard Children's Hospital at Stanford | Palo Alto | California | United States | 94304 |
| 3 | Sutter Cancer Center | Sacramento | California | United States | 95816 |
| 4 | Kaiser Permanente-Southern California Permanente Medical Group | San Diego | California | United States | 92120 |
| 5 | Naval Medical Center - San Diego | San Diego | California | United States | 92134-3202 |
| 6 | Kaiser Permanente Medical Center - Santa Clara | Santa Clara | California | United States | 95051-5386 |
| 7 | Nemours Children's Clinic | Jacksonville | Florida | United States | 32207 |
| 8 | Mount Sinai Comprehensive Cancer Center | Miami Beach | Florida | United States | 33140 |
| 9 | Sylvester Cancer Center, University of Miami | Miami | Florida | United States | 33136 |
| 10 | Baptist Hospital of Miami | Miami | Florida | United States | 33176-2197 |
| 11 | Walt Disney Memorial Cancer Institute | Orlando | Florida | United States | 32803 |
| 12 | St. Mary's Hospital | West Palm Beach | Florida | United States | 33407 |
| 13 | Emory University Hospital - Atlanta | Atlanta | Georgia | United States | 30322 |
| 14 | Tripler Army Medical Center | Honolulu | Hawaii | United States | 96859-5000 |
| 15 | Rush-Presbyterian-St. Luke's Medical Center | Chicago | Illinois | United States | 60612 |
| 16 | Children's Memorial Hospital, Chicago | Chicago | Illinois | United States | 60614 |
| 17 | Hope Children's Hospital | Oak Lawn | Illinois | United States | 60453 |
| 18 | Saint Jude Midwest Affiliate | Peoria | Illinois | United States | 61602 |
| 19 | Via Christi Regional Medical Center | Wichita | Kansas | United States | 67214 |
| 20 | Tulane University School of Medicine | New Orleans | Louisiana | United States | 70112 |
| 21 | Eastern Maine Medical Center | Bangor | Maine | United States | 04401 |
| 22 | Maine Children's Cancer Program | Portland | Maine | United States | 04101 |
| 23 | Massachusetts General Hospital Cancer Center | Boston | Massachusetts | United States | 02114 |
| 24 | St. John's Hospital and Medical Center | Detroit | Michigan | United States | 48236 |
| 25 | Hurley Medical Center | Flint | Michigan | United States | 48503 |
| 26 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216-4505 |
| 27 | Keesler Medical Center - Keesler AFB | Keesler AFB | Mississippi | United States | 39534-2576 |
| 28 | University of Missouri-Columbia Hospital and Clinics | Columbia | Missouri | United States | 65212 |
| 29 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 30 | Norris Cotton Cancer Center | Lebanon | New Hampshire | United States | 03756 |
| 31 | University of New Mexico School of Medicine | Albuquerque | New Mexico | United States | 87131 |
| 32 | State University of New York Health Sciences Center - Stony Brook | Stony Brook | New York | United States | 11790-7775 |
| 33 | Duke Comprehensive Cancer Center | Durham | North Carolina | United States | 27710 |
| 34 | Oklahoma Memorial Hospital | Oklahoma City | Oklahoma | United States | 73126-0307 |
| 35 | Natalie Warren Bryant Cancer Center | Tulsa | Oklahoma | United States | 74136 |
| 36 | James H. Quillen College of Medicine | Johnson City | Tennessee | United States | 37614-0622 |
| 37 | Medical City Dallas Hospital | Dallas | Texas | United States | 75230 |
| 38 | Simmons Cancer Center - Dallas | Dallas | Texas | United States | 75235-9154 |
| 39 | Cook Children's Medical Center - Fort Worth | Fort Worth | Texas | United States | 76104 |
| 40 | University of Texas Medical Branch | Galveston | Texas | United States | 77555-0209 |
| 41 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
| 42 | San Antonio Military Pediatric Cancer and Blood Disorders Center | Lackland Air Force Base | Texas | United States | 78236-5300 |
| 43 | Scott and White Clinic | Temple | Texas | United States | 76508 |
| 44 | Vermont Cancer Center | Burlington | Vermont | United States | 05401-3498 |
| 45 | Inova Fairfax Hospital | Falls Church | Virginia | United States | 22046 |
| 46 | Carilion Roanoke Community Hospital | Roanoke | Virginia | United States | 24029 |
| 47 | Madigan Army Medical Center | Tacoma | Washington | United States | 98431-5000 |
| 48 | West Virginia University Medical School, Charleston Division | Charleston | West Virginia | United States | 25304 |
| 49 | West Virginia University Hospitals | Morgantown | West Virginia | United States | 26506-9162 |
| 50 | St. Vincent Hospital | Green Bay | Wisconsin | United States | 54307-3508 |
| 51 | Midwest Children's Cancer Center | Milwaukee | Wisconsin | United States | 53226 |
| 52 | Alberta Children's Hospital | Calgary | Alberta | Canada | T2T 5C7 |
| 53 | Children's Hospital of Eastern Ontario | Ottawa | Ontario | Canada | K1H 8L1 |
| 54 | Montreal Children's Hospital | Montreal | Quebec | Canada | H3H 1P3 |
| 55 | Centre Hospitalier de L'Universite Laval | Sainte Foy | Quebec | Canada | GIV 4G2 |
| 56 | Academisch Ziekenhuis Groningen | Groningen | Netherlands | 9713 EZ | |
| 57 | San Jorge Childrens Hospital | Santurce | Puerto Rico | 00912 | |
| 58 | Clinique de Pediatrie | Geneva | Switzerland | 1211 |
Sponsors and Collaborators
- Children's Oncology Group
- National Cancer Institute (NCI)
Investigators
- Study Chair: William P. Bowman, MD, Cook Children's Medical Center - Fort Worth
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 9806
- POG-9806
- CDR0000066915