A Phase I Trial Of Sequential Administration Of Triapine (3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone) Followed By Fludarabine In Adults With Relapsed And Refractory Leukemias And Myelodysplasias

Date de début de l'étude : 1 janvier 2004

DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of 1 of the following: * High-risk myelodysplastic syndromes (MDS), including refractory anemia with excess blasts and chronic myelomonocytic leukemia * International Prognostic Scoring System (IPSS) score at least 1.5 based on the following: * More than 10% marrow blasts * Cytopenias in at least 2 lineages * Adverse cytogenetics * Acute myeloid leukemia (AML) * All subtypes, including MDS/AML and treatment-related (secondary) AML * Acute lymphoblastic leukemia * Acute progranulocytic leukemia * Ineligible for arsenic therapy * Chronic myelogenous leukemia * Accelerated phase or blastic crisis * Chronic lymphocytic leukemia * Prolymphocytic leukemia * Received or ineligible for established curative regimens, including stem cell transplantation * Acute and chronic leukemias must be relapsed and/or refractory with progressive disease since last therapy PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 Life expectancy * Not specified Hematopoietic * No history of hemolytic anemia grade 2 or greater * No known glucose-6-phosphate dehydrogenase (G6PD) deficiency * G6PD screening required for high-risk groups (i.e., patients of African, Asian, or Mediterranean origin/ancestry) Hepatic * SGOT and SGPT no greater than 2.5 times normal * Bilirubin no greater than 2 mg/dL * No chronic hepatitis Renal * Creatinine normal OR * Creatinine clearance at least 60 mL/min Cardiovascular * No active heart disease * No myocardial infarction within the past 3 months * No severe coronary artery disease * No arrhythmias (other than atrial flutter or fibrillation) requiring medication * No uncontrolled congestive heart failure Pulmonary * No dyspnea at rest or with minimal exertion * No severe pulmonary disease requiring supplemental oxygen Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No neuropathy grade 2 or greater * No active uncontrolled infection * Infections under active treatment and controlled by antibiotics are allowed * No other life-threatening illness * No psychiatric illness that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * See Disease Characteristics * At least 1 week since prior hematopoietic growth factor (e.g., epoetin alfa, filgrastim \[G-CSF\], sargramostim \[GM-CSF\], interleukin-3, and interleukin-11) * No concurrent immunotherapy Chemotherapy * Recovered from prior chemotherapy (no greater than grade 1 chronic toxic effects) * At least 72 hours since prior hydroxyurea * At least 3 weeks since prior myelosuppressive cytotoxic agents (6 weeks for mitomycin or nitrosoureas) * No more than 12 prior courses of fludarabine * No more than 3 prior cytotoxic chemotherapy regimens * No other concurrent chemotherapy Endocrine therapy * Not specified Radiotherapy * At least 2 weeks since prior radiotherapy * No concurrent radiotherapy Surgery * Not specified Other * At least 1 week since prior non-myelosuppressive treatment * No more than 4 prior induction regimens * No other concurrent therapy