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
Data Collection
Bone Marrow Diseases+10
+ Disease
+ Hematologic Diseases
Treatment Study
Summary
Study start date: January 1, 2004
Actual date on which the first participant was enrolled.OBJECTIVES: * Determine the feasibility and tolerability of 3-AP (Triapine\^® ) followed by fludarabine in patients with relapsed or refractory acute or chronic leukemia or high-risk myelodysplastic syndromes. * Determine the toxic effects of this regimen in these patients. * Determine the maximum tolerated dose of this regimen in these patients. OUTLINE: This is a multicenter, dose-escalation study of fludarabine. Patients are stratified according to disease (acute leukemias and myelodysplastic syndromes \[MDS\] vs chronic lymphocytic leukemia and prolymphocytic leukemia). Patients are assigned to 1 of 2 treatment groups. * Group 1 (chronic lymphocytic leukemia or prolymphocytic leukemia): Patients receive 3-AP (Triapine\^®) IV over 4 hours and fludarabine IV over 30 minutes on days 1-5. Cohorts of 3-6 patients receive escalating doses of fludarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 10 additional patients are treated at that dose level. * Group 2 (acute leukemias or MDS): Patients receive 3-AP IV continuously over 24 hours on day 1. Beginning within 4 hours after completion of 3-AP, patients receive fludarabine IV over 30 minutes on days 2-6. In both groups, treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. PROJECTED ACCRUAL: A total of 3-34 patients will be accrued for this study.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
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
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 4 locations
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, United StatesSidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, United StatesM.D. Anderson Cancer Center at University of Texas
Houston, United States