Trial Information

ACUTE MYELOID LEUKEMIA SALVAGE THERAPY FOR PATIENTS IN FIRST RELAPSE OR WHO FAIL TO ACHIEVE AN INITIAL REMISSION OR WHO DEVELOP ACUTE MYELOID LEUKEMIA AS A SECOND MALIGNANT NEOPLASM

OBJECTIVES: I. Determine the toxicity, remission rate, event-free survival, and overall
survival following induction with cytarabine/mitoxantrone (ARA-C/DHAD), intensification with
ARA-C and etoposide (VP-16), and consolidation with cladribine (2-CdA) and VP-16 in patients
with acute myeloid leukemia (AML) that is secondary, in first relapse, or has failed initial
remission induction therapy. II. Compare the remission induction rate and event-free
survival on this trial with prior second-line studies (i.e., protocols CCG-243, CCG-201, and
CCG-261P). III. Compare survival of patients on this trial with the survival of patients
relapsing or failing to achieve an initial complete remission (CR) on previous front-line
AML trials (i.e., protocols CCG-251, CCG-213, CCG-2861, and CCG-2891). IV. Determine the
frequency and prognostic significance of mdr1 gene expression and p53, topoisomerase II, and
deoxycytidine kinase gene mutations in these patients. V. Determine the disease-free and
overall survival of patients achieving a CR on this study in relation to the
post-intensification therapy received (i.e., bone marrow transplantation, chemotherapy, or
no further therapy). VI. Determine the frequency and degree of abnormal cardiac function on
echocardiogram or MUGA at 1 and 5 years in patients treated with mitoxantrone following
anthracycline therapy during initial treatment. VII. Provide a control arm evaluating the
safety of using phase I or II agents in an "upfront window" approach planned for future CCG
studies. VIII. Determine the toxicity, remission rate, event-free survival, and overall
survival in patients who fail to achieve a CR with ARA-C/DHAD induction and are then treated
with 2-CdA/VP-16. IX. Determine the biologic characteristics, toxicity, remission rate,
event-free survival, and overall survival following this treatment regimen in patients who
develop AML as a second malignancy.

OUTLINE: Patients who do not achieve M1/M2a marrow following Induction proceed to Salvage
Induction; all others proceed to Intensification. Patients receive Consolidation therapy on
Regimen A, B, or C according to the investigator's choice. The following acronyms are used:
ARA-C Cytarabine, NSC-63878 2-CdA Cladribine (2-Chlorodeoxyadenosine), NSC-105014 DHAD
Mitoxantrone, NSC-301739 G-CSF Filgrastim, NSC-614629 HC Hydrocortisone, NSC-10483 HD High
Dose MTX Methotrexate, NSC-740 PBSC Peripheral Blood Stem Cells TBI Total-Body Irradiation
TIT Triple Intrathecal Therapy (IT ARA-C/IT HC/IT MTX) VP-16 Etoposide, NSC-141540
INDUCTION: 2-Drug Combination Chemotherapy plus CNS Prophylaxis/Therapy. ARA-C/DHAD; G-CSF;
plus IT ARA-C and, if CNS disease at entry, TIT. SALVAGE INDUCTION: 2-Drug Combination
Chemotherapy. 2-CdA/VP-16. INTENSIFICATION: 2-Drug Combination Chemotherapy followed, as
indicated, by Radiotherapy. HD ARA-C/VP-16; followed, in patients with persistent CNS
disease, CNS relapse, or chloromas, by irradiation using megavoltage equipment (minimum Co60
and maximum 6 MV x-rays or electrons). CONSOLIDATION: Regimen A: 2-Drug Combination
Chemotherapy. 2-CdA/VP-16. Regimen B: Myeloablative Chemoradiotherapy followed by
Hematopoietic Rescue. TBI (equipment unspecified) with electron boosts to the testes, chest,
extramedullary sites, and, if indicated, craniospinal region; VP-16; followed by allogeneic
or autologous bone marrow or PBSC. Regimen C: No further therapy.

PROJECTED ACCRUAL: A total of 90 patients will be entered. The study may be closed if there
are 7 or more deaths in the first 45 patients who complete Intensification.