Phase I Trial of Sequential Topotecan(NSC 609699)and Etoposide for Patients With Relapsed, Refractory,or High Risk Acute Myeloid or Lymphoid Leukemia
etoposide
+ topotecan hydrochloride
Bone Marrow Diseases+26
+ Cell Transformation, Neoplastic
+ Chronic Disease
Treatment Study
Summary
Study start date: August 1, 1994
Actual date on which the first participant was enrolled.OBJECTIVES: I. Determine the maximum tolerated dose of topotecan when combined with etoposide in patients with relapsed or refractory acute myelogenous leukemia, acute lymphoblastic leukemia, or blastic phase chronic myelogenous leukemia. II. Determine the toxicity of this regimen in these patients. III. Measure serum levels of topotecan at steady state and correlate them with any change in topoisomerase II content in leukemic blasts. IV. Assess whether it is feasible to correlate any upregulation of topoisomerase II expression with tumor response to etoposide in subsequent Phase II studies. V. Assess whether levels of pretreatment expression of topoisomerases I and II in leukemic cells are predictive of clinical response. VI. Assess whether it is feasible to develop a pharmacodynamic assay based on posttreatment apoptotic changes in leukemic blasts and whether this could be correlated with tumor response in subsequent phase II trials. VII. Determine the response in patients treated with this regimen. OUTLINE: Induction: 2-Drug Combination Chemotherapy. Topotecan, TOPO, NSC-609699; Etoposide, VP-16, NSC-141540. Consolidation: 2-Drug Combination Chemotherapy. TOPO; VP-16. PROJECTED ACCRUAL: 15-23 patients will be accrued in approximately 18 months.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.30 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.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: Acute myelogenous leukemia (M0-M7) and acute lymphoblastic leukemia (L1-L2) Refractory or in first or subsequent relapse Circulating blasts present OR Greater than 5% blasts in bone marrow Acute myelogenous leukemia secondary to myelodysplastic syndrome or cytotoxic therapy Untreated OR Maximum of 2 intensive induction regimens Chronic myelogenous leukemia in blastic or lymphoid crisis Untreated OR Maximum of 2 intensive induction regimens No CNS leukemia PATIENT CHARACTERISTICS: Age: Over 18 Performance status: ECOG 0-3 Life expectancy: At least 4 weeks Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL AST and ALT less than 3 times normal Alkaline phosphatase less than 3 times normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular: No myocardial infarction within 6 months No active ischemic cardiac disease No poorly controlled congestive heart failure No other symptomatic cardiac disease Left ventricular ejection fraction at least 40% Pulmonary: No symptomatic restrictive or obstructive lung disease Other: No severe neurologic disease No active infection unless stable on antimicrobial therapy or fever is tumor related HIV negative Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: At least 2 weeks since prior cytotoxic therapy (except hydroxyurea and steroids) Biologic therapy: No prior bone marrow transplantation At least 3 days since prior hematopoietic growth factors Chemotherapy: No prior topotecan or camptothecin analogues Prior etoposide allowed Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.Study Objectives
Primary Objectives
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 1 location
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, United StatesOpen Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center in Google Maps