Phase II Study of Intensive Postremission Therapy with High-Dose ARA-C, CTX/VP-16, and DHAD/AZQ Following Induction with ARA-C/DNR in Patients with Acute Myeloid Leukemia

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IITreatmentClosed15 to under 60NCICLB-9022


I.  Determine the feasibility of administering high-dose cytarabine, 
cyclophosphamide/etoposide, and mitoxantrone/diaziquone (DHAD/AZQ) as three 
intensive postremission courses to patients with acute myeloid leukemia in 
first remission after treatment with standard induction chemotherapy 
II.  Test the effectiveness of granulocyte colony stimulating factor (G-CSF) 
in stimulating normal myeloid recovery after completion of DHAD/AZQ.
III.  Define a tolerable combination of DHAD/AZQ or AZQ alone with G-CSF which 
allows a duration of neutropenia of no more than 28 days.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients 15 to less than 60 years of 
age with an unequivocal histologic diagnosis of acute myeloid leukemia of any 
of the following histologies (FAB classifications M1-7):  myelocytic without 
or with maturation, promyelocytic, myelomonocytic, monocytic, erythroleukemia, 
and megakaryocytic.  Bone marrow must show at least 30% replacement of 
nonerythroid elements by blasts, and at least one of the following 
characteristics of leukemia cells must be present:  Auer rods, peroxidase- or 
Sudan black-positive blasts, chloracetate esterase- or nonspecific 
esterase-positive blasts, or ultrastructural platelet peroxidase or platelet 
antigens (as detected by monoclonal antibodies).  Unstained slides of 
pretreatment marrow and blood for cytochemistry must be submitted for review.  
Patients with undifferentiated leukemia, M0 AML, or CNS leukemia (LP is not 
required at diagnosis and is done only if indicated symptomatically) are 
specifically excluded, as are those with a prior history of any antecedent 
hematologic malignancy, polycythemia vera, paroxysmal nocturnal 
hemoglobinuria, and preleukemic syndrome.  There must have been no prior 
radiotherapy or cytotoxic chemotherapy except with hydroxyurea or 
corticosteroids; any concurrent medical condition that requires chronic use of 
corticosteroids excludes.  There must be no evidence of pre-existing liver 
disease, and adequate liver and kidney function must be demonstrated as 
follows (unless elevated values are directly attributable to AML):  bilirubin 
no more than 1.5 x normal and alkaline phosphatase, SGOT, and SGPT no more 
than 2 x normal; and creatinine no more than 1.5 x normal.  The following 
conditions exclude:  myocardial infarction within the previous year; active 
uncontrolled infection; uncontrolled diabetes mellitus; or prior or 
concomitant malignancy other than inactive nonmelanomatous skin cancer, in 
situ carcinoma of the cervix, or other cancer from which the patient has been 
disease free for at least 5 years.  Patients must be managed through a medical 
facility with ready access to blood product support and adequate staffing to 
care for febrile, neutropenic patients.  Concurrent entrance on ancillary 
protocols CLB-8461, CLB-8361, CLB-8362, and CLB-8765 is strongly recommended.

Expected Enrollment

A total of 220 patients will be entered; 25 patients will be studied on each 
of 4 variations of Intensification 3.


Nonrandomized study.
Induction:  2-Drug Combination Chemotherapy.  Daunorubicin, DNR, NSC-82151; 
Cytarabine, Cytosine arabinoside, ARA-C, NSC-63878.
Intensification 1:  Single-agent Chemotherapy.  High-dose ARA-C.
Intensification 2:  2-Drug Combination Chemotherapy.  Etoposide, VP-16, 
NSC-141540; Cyclophosphamide, CTX, NSC-26271.
Intensification 3:  2-Drug Combination or Single-agent Chemotherapy with 
Hematologic Toxicity Attenuation.  Diaziquone, AZQ, NSC-182986; with or 
without Mitoxantrone, DHAD, NSC-301739; with Granulocyte Colony Stimulating 
Factor (Amgen); G-CSF; NSC-614629.

Published Results

Moore JO, Schiffer CA, Amrein PC, et al.: G-CSF dramatically reduces the duration of both granulocytopenia and thrombocytopenia after AZQ/mitoxantrone consolidation in acute myelogenous leukemia: CALGB 9022. Blood 80(10 Suppl): 291a, 1992.

Related Publications

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

Joseph Moore, MD, Protocol chair
Ph: 919-684-3377

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.