|Phase III||Treatment||Completed||21 and under||NCI||POG-8821|
I. Determine the disease-free survival and event-free survival of previously untreated children with acute myelocytic leukemia (AML) treated with induction therapy consisting of DAT (daunomycin/cytosine arabinoside/6-thioguanine) followed by high-dose cytosine arabinoside and seven courses of alternating non-cross resistant consolidation chemotherapy consisting of etoposide/azacytidine followed by high-dose cytosine arabinoside followed by DAT. II. Compare the treatment outcome of patients randomized to the above consolidation regimen with that of patients randomized to consolidation consisting of one course of etoposide/azacytidine followed by autologous bone marrow therapy using the busulfan/cyclophosphamide preparative regimen and marrow purged with 4-hydroxyperoxycyclophosphamide. III. Correlate treatment outcome with clinical and laboratory features.
Previously untreated acute myelocytic leukemia (M1-M7), with or without granulocytic sarcoma Previously untreated granulocytic sarcoma with normal bone marrow (not over 25% blasts) also eligible CNS disease allowed Appropriate FAB classification studies and cytochemical stains required Cytocentrifuge and tissue slides required for CNS disease or isolated granulocytic sarcoma at presentation Prior hematopoietic disease or prior malignancy allowed (including appropriate antineoplastic therapy)
Biologic therapy: No prior therapy for current disease Chemotherapy: No prior chemotherapy for AML Prior cumulative anthracycline dose no more 250 mg/sqm (in patients with prior antineoplastic therapy for prior malignancy) Endocrine therapy: No prior therapy for current disease Radiotherapy: No prior therapy for current disease Surgery: No prior therapy for current disease
Age: No more than 21 Performance status: Not specified Hematopoietic: No extreme hyperleukocytosis (100,000 or more) requiring leukapheresis or exchange transfusion (study coordinator should be notified if there is any question) Hepatic: Bilirubin less than 1.2 mg/dl Renal: Creatinine less than 1.2 mg/dl Uric acid less than 8.0 mg/dl Cardiovascular: Normal cardiac function demonstrated by MUGA or echocardiogram if history of prior anthracycline therapy Other: No proven or suspected sepsis or significant infection
In order to accrue the required 75 patients per randomization arm, it is estimated that entry of 76 patients/year will be required and that the total accrual period will be about 2.5 years.
All patients receive identical Induction therapy; those who achieve CR are randomized for Consolidation on Arms I and II (patients who are not eligible for the transplant arm are assigned nonrandomly to Arm I). While allogeneic bone marrow transplantation is not an integral part of this protocol, this option is available to patients with a suitable donor should it be desired; the timing of allogeneic marrow transplant is the same as for autologous marrow transplant, and it is suggested that the preparative regimen be the same. Patients undergoing allogeneic marrow transplant remain on study and continue to be followed for eventual outcome. Induction: 3-Drug Combination Systemic Chemotherapy plus Single-agent Intrathecal Chemotherapy followed by Single-agent High-Dose Systemic Chemotherapy. DAT: Daunomycin, Daunorubicin, DNM, NSC-82151; Cytosine arabinoside, Cytarabine, ARA-C, NSC-63878; Thioguanine, 6-TG, NSC-752; plus intrathecal ARA-C; followed by High-dose ARA-C. Consolidation. Arm I: Alternating Courses of Combination and Single-agent Systemic Chemotherapy plus Intrathecal Chemotherapy. Etoposide, VP-16, NSC-141540; Azacytidine, AZC, NSC-102816; alternating with High-dose ARA-C with or without DNM; alternating with DAT; plus intrathecal ARA-C. Arm II: 2-Drug Combination Systemic Chemotherapy plus Single-agent Intrathecal Chemotherapy followed (on POG-8822) by Marrow Ablation with 2-Drug Combination Chemotherapy followed by Autologous Bone Marrow Therapy. VP-16; AZC; plus intrathecal ARA-C; followed by Busulfan, BU, NSC-750; Cyclophosphamide, CTX, NSC-26271; followed by reinfusion of autologous marrow treated with 4-Hydroperoxycyclophosphamide (4-HC).Published Results
Parsons SK, Gelber S, Cole BF, et al.: Quality-adjusted survival after treatment for acute myeloid leukemia in childhood: A Q-TWiST analysis of the Pediatric Oncology Group Study 8821. J Clin Oncol 17 (7): 2144-52, 1999.[PUBMED Abstract]
Raimondi SC, Chang MN, Ravindranath Y, et al.: Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821. Blood 94 (11): 3707-16, 1999.[PUBMED Abstract]
Ravindranath Y, Yeager AM, Chang MN, et al.: Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood. Pediatric Oncology Group. N Engl J Med 334 (22): 1428-34, 1996.[PUBMED Abstract]
Ravindranath Y, Yeager A, Krischer J, et al.: Intensive consolidation chemotherapy (ICC) vs purged autologous bone marrow transplantation (ABMT) early in remission for treatment of childhood acute myeloid leukemia (AML): preliminary results of Pediatric Oncology Group (POG) study 8821. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-1053, 320, 1994.
Ravindranath Y, Abella E, Krischer J, et al.: Acute myeloid leukemia (AML) in Down syndrome (DS): response and toxicity with high dose arabinosyl cytosine (ARA-C). [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-1071, 323, 1993.Related Publications
Horan JT, Alonzo TA, Lyman GH, et al.: Impact of disease risk on efficacy of matched related bone marrow transplantation for pediatric acute myeloid leukemia: the Children's Oncology Group. J Clin Oncol 26 (35): 5797-801, 2008.[PUBMED Abstract]
Ravindranath Y, Chang M, Steuber CP, et al.: Pediatric Oncology Group (POG) studies of acute myeloid leukemia (AML): a review of four consecutive childhood AML trials conducted between 1981 and 2000. Leukemia 19 (12): 2101-16, 2005.[PUBMED Abstract]
Taub JW, Matherly LH, Stout ML, et al.: Enhanced metabolism of 1-beta-D-arabinofuranosylcytosine in Down syndrome cells: a contributing factor to the superior event free survival of Down syndrome children with acute myeloid leukemia. Blood 87 (8): 3395-403, 1996.[PUBMED Abstract]
Abella E, Katz J, Ravindranath Y, et al.: Toxicity with high dose cytarabine (ARA-C) in children: experience on Pediatric Oncology Group (POG) leukemia/lymphoma studies. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-1052, 320, 1994.
Trial Lead Organizations
Pediatric Oncology Group
|Yaddanapudi Ravindranath, MBBS, Protocol chair|
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.