Phase III Randomized Study of Extended Chemotherapy Using Non-Cross Resistant Drug Combinations vs Abbreviated Chemotherapy Followed by Autologous Bone Marrow Therapy in Children with AML
Basic Trial Information
|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).
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Trial Contact Information
Trial Lead Organizations
Pediatric Oncology Group
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