Phase III Comparison of the Effect of Post-Remission Intensification with Intermittent High-Dose vs Continuous High-Dose vs Continuous Low-Dose ARA-C on CR Duration in Adults with ANLL Who Achieve First Remission Following DNM/ARA-C Induction
Basic Trial Information
|Phase III||Treatment||Closed||15 through 59||NCI||CLB-8525|
I. Evaluate the effect on the duration of CR of intensive post-remission cytosine arabinoside when administered as part of an 8-course consolidation regimen and compared to a lower-dose cytosine arabinoside program in adults with ANLL in first remission. II. Compare the effect on the duration of CR of intermittent high-dose cytosine arabinoside vs. a continuous high-dose infusion of cytosine arabinoside as part of an intensive post-remission regimen in patients with ANLL.
See General Eligibility Criteria
See General Eligibility Criteria
General Eligibility Criteria:
Patients aged 15 through 59 years with an unequivocal histologic diagnosis of ANLL based on FAB classification of one of the following histologies: acute myelocytic leukemia without (M-1) or with (M-2) maturation; acute promyelocytic leukemia (M-3); acute myelomonocytic leukemia (M-4); acute monocytic leukemia (M-5); acute erythroleukemia (M-6); and acute megakaryoblastic leukemia (M7). Patients must demonstrate at least 1 of the following characteristics: Auer rods; peroxidase- or sudan black-positive blasts; chloracetate esterase- or nonspecific esterase-positive blasts; or, in patients with M7 leukemia, by the presence of ultrastructural platelet peroxidase or by the detection of platelet antigens using monoclonal antibodies. The bone marrow must reveal at least 50% replacement of nonerythroid elements by blasts and/or promyelocytes or at least 25% replacement of nonerythroid elements by blasts and/or promyelocytes if accompanied by neutropenia (fewer than 1,000 granulocytes and bands) and/or thrombocytopenia (fewer than 50,000). Unstained slides of the pretreatment bone marrow must be submitted for cytochemistry review. Adequate liver and kidney function must be documented as follows: bilirubin no more than 3.0 mg/dl; alkaline phosphatase, SGOT, and SGPT each less than twice normal; and serum creatinine less than 2.0 mg/dl. There may be no prior radiotherapy and no history of any antecedent hematologic malignancy, including polycythemia vera, paroxysmal nocturnal hemaglobinuria, and the preleukemic syndrome. There may have been no previous nonsteroidal cytotoxic chemotherapy aside from hydroxyurea, and patients must be free from uncontrolled infection. There may be no pre-existing liver disease and/or alcohol abuse, no uncontrolled diabetes mellitus, and no history of myocardial infarction within one year.
725 patients will be required. As of December, 1987, it was anticipated that the necessary accrual will have been completed by the fall of 1989. As of March 1989, the total sample size was revised to 820 patients because the proportion of patients being randomized (less than 54%) was less than anticipated.
All patients recieve Induction therapy, following which patients in CR under the age of 60 at the time of randomization are randomized on Arms I, II and III and those 60 and over are randomized on Arms II and III. Following the randomized Intensification I, all patients receive identical therapy on Intensification II. Induction: 2-Drug Combination Chemotherapy. Daunomycin, DNM, NSC-82151; Cytosine arabinoside, ARA-C, NSC-63878. Intensification I. Arm I: Single-agent Chemotherapy. ARA-C. Intermittent high-dose schedule. Arm II: Single-agent Chemotherapy. ARA-C. Continuous high-dose schedule. Arm III: Single-agent Chemotherapy. ARA-C. Continuous low-dose schedule. Intensification II: 2-Drug Combination Chemotherapy. DNM; ARA-C.
Neubauer A, Maharry K, Mrózek K, et al.: Patients with acute myeloid leukemia and RAS mutations benefit most from postremission high-dose cytarabine: a Cancer and Leukemia Group B study. J Clin Oncol 26 (28): 4603-9, 2008.[PUBMED Abstract]
Neubauer A, Maharry K, Marcucci G, et al.: Patients (pts) with acute myeloid leukemia (AML) and mutant RAS benefit from high-dose cytarabine (HDAC) intensification: a Cancer and Leukemia Group B (CALGB) study. [Abstract] J Clin Oncol 23 (Suppl 16): A-6514, 563s, 2005.
Mayer RJ, Davis RB, Schiffer CA, et al.: Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med 331 (14): 896-903, 1994.[PUBMED Abstract]
Mayer RJ, Davis RB, Schiffer CA, et al.: Comparative evaluation of intensive postremission therapy with different dose schedules of ARA-C in adults with acute myeloid leukemia: initial results of a CALGB phase III study. [Abstract] Proceedings of the American Society of Clinical Oncology 11: A-853, 261, 1992.
Mayer RJ, Davis RB, Schiffer CA, et al.: Comparative evaluation of intensive post-remission therapy with different dose schedules of ARA-C in adults with acute myeloid leukemia: initial results of a CALGB phase III study. Ann Hematol 64(Suppl): A-113, 1992.
Mayer RJ, Davis RB, Schiffer CA, et al.: Intensive post-remission therapy with Ara-C in adults with acute myeloid leukemia: initial results of a CALGB phase III trial. The Cancer and Leukemia Group B. Leukemia 6 (Suppl 2): 66-7, 1992.[PUBMED Abstract]
Marcucci G, Maharry K, Wu YZ, et al.: IDH1 and IDH2 gene mutations identify novel molecular subsets within de novo cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. J Clin Oncol 28 (14): 2348-55, 2010.[PUBMED Abstract]
Paschka P, Marcucci G, Ruppert AS, et al.: Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B Study. J Clin Oncol 24 (24): 3904-11, 2006.[PUBMED Abstract]
Sekeres MA, Peterson B, Dodge RK, et al.: Differences in prognostic factors and outcomes in African Americans and whites with acute myeloid leukemia. Blood 103 (11): 4036-42, 2004.[PUBMED Abstract]
Byrd JC, Mrózek K, Dodge RK, et al.: Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 100 (13): 4325-36, 2002.[PUBMED Abstract]
Sekeres MA, Dodge RK, Bloomfield CD, et al.: Racial differences in prognostic factors and outcome in acute myeloid leukemia (AML): a Cancer and Leukemia Group B (CALGB) study. [Abstract] Blood 100 (11 Pt 1): A-323, 2002.
Trial Contact Information
Trial Lead Organizations
Cancer and Leukemia Group B
Ph: 617-632-3474; 866-790-4500
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.