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
Basic Trial Information
|Phase II||Treatment||Closed||15 to under 60||NCI||CLB-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 (cytarabine/daunorubicin). 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.
See General Eligibility Criteria
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.
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.
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.
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
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.