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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
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentClosed15 through 59NCICLB-8525
CALGB-8525

Objectives

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.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

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.

Expected Enrollment

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.

Outline

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.

Published Results

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]

Related Publications

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.

Bernstein SH, Brunetto VL, Davey FR, et al.: Intensive chemotherapy for patients with myelodysplastic syndromes (MDS). [Abstract] Blood 82(10 suppl 1): A769, 196a, 1993.

Weiss RB: A third anthracycline for acute leukemia. Contemp Oncol 2: 30-39, 1992.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Robert Mayer, MD, FACP, Protocol chair
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.

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