A PHASE I COOPERATIVE AGREEMENT PEDIATRIC TRIAL OF MITOXANTRONE, ETOPOSIDE AND PSC-833 (PSC-ME) THERAPY IN PATIENTS WITH RELAPSED AND REFRACTORY ACUTE LEUKEMIA
etoposide
+ mitoxantrone hydrochloride
+ valspodar
Hematologic Diseases+8
+ Hemic and Lymphatic Diseases
+ Immune System Diseases
Treatment Study
Summary
Study start date: January 1, 1997
Actual date on which the first participant was enrolled.OBJECTIVES: I. Determine the maximum tolerated dose of PSC-833 in combination with mitoxantrone and etoposide in children with refractory or relapsed acute leukemia. II. Determine the effects of PSC-833 on mitoxantrone and etoposide pharmacokinetics. III. Quantify MDR1 gene expression and MDR1 P-glycoprotein expression and function in patient-derived leukemia cells. OUTLINE: This is a dose escalation study of PSC-833. Patients undergo induction therapy consisting of etoposide IV and mitoxantrone IV on days 1-5. Patients then receive PSC-833 IV over 124 hours beginning on day 2. A second course is administered no sooner than 21 days from the start of the first course if the marrow is hypocellular after the first course. Patients with persistent disease after 2 induction courses are removed from the study. Patients receive a total of 3 courses of etoposide/mitoxantrone. Patients who achieve complete remission after 1 induction course receive 2 courses of etoposide/mitoxantrone with PSC-833 as consolidation, beginning within 4 weeks of attainment of complete remission. Patients who achieve complete remission after 2 induction courses receive 1 course of etoposide/mitoxantrone with PSC-833 as consolidation. Cohorts of 3-6 patients receive escalating doses of PSC-833 until the maximum tolerated dose is determined. Patients are followed every 6 months.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.3 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.Until 21 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 myeloid leukemia (AML) in one of the following categories: First relapse if initial CR less than 6 months Refractory to first or second induction with daunomycin, cytarabine, and thioguanine (DAT) or other anthracycline-containing regimens Relapse following bone marrow transplantation provided good trilineage engraftment followed transplant and greater than 6 months since transplant Presentation with secondary AML or AML evolving from myelodysplastic syndrome --Acute lymphocytic leukemia in one of the following categories: In second or subsequent relapse or failed second or later induction attempts regardless of prior remissions Relapsed following bone marrow transplantation provided good trilineage engraftment followed transplant and greater than 6 months since transplant No isolated CNS or extramedullary relapse PATIENT CHARACTERISTICS: Age: Under 22 at diagnosis Performance status: Karnofsky 50-100% (ECOG 0-2) Lansky 40-100% (in patients under 12 years of age) Life expectancy: At least 8 weeks Bilirubin less than 1.5 mg/dL ALT less than twice normal Creatinine normal for age (within 2 standard deviations) OR glomular filtration rate at least 70 mL/min Albumin at least 3 g/dL Ejection fraction greater than 50% at rest or with 5% increase with exercise OR shortening fraction greater than 27% by echocardiogram No history of clinical heart failure No uncontrolled infection No anticonvulsant therapy No history of allergic reactions or anaphylaxis to etoposide not remediable by premedication Not pregnant or nursing Fertile patients must use effective contraception Third percentile weight for height PRIOR CONCURRENT THERAPY: At least 4 weeks since chemotherapy and recovered Prior cumulative anthracycline dose no greater than 360 mg per square meter Hydroxyurea therapy allowed just prior to study for rapidly rising blast count
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy 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 55 locations
University of Arkansas for Medical Sciences
Little Rock, United StatesOpen University of Arkansas for Medical Sciences in Google MapsUniversity of California San Diego Cancer Center
La Jolla, United StatesChildren's Hospital Los Angeles
Los Angeles, United StatesJonsson Comprehensive Cancer Center, UCLA
Los Angeles, United States