AML-MVPCYA: ADDITION OF CYCLOSPORIN A TO THE COMBINATION OF MITOXANTRONE AND ETOPOSIDE (VP 16,213) TO OVERCOME RESISTANCE TO CHEMOTHERAPY IN REFRACTORY AML: A RANDOMIZED PHASE II STUDY
cyclosporine
+ etoposide
+ mitoxantrone hydrochloride
Hematologic Diseases+4
+ Hemic and Lymphatic Diseases
+ Leukemia, Myeloid
Treatment Study
Summary
Study start date: February 1, 1995
Actual date on which the first participant was enrolled.OBJECTIVES: I. Evaluate whether the addition of cyclosporine (CYSP) to mitoxantrone (DHAD) and etoposide (VP-16) increases the response rate and duration of response in adults with refractory or relapsed acute myelogenous leukemia (AML). II. Correlate response to this treatment with the presence of P-glycoprotein (P-gp) multidrug resistance (MDR) and the degree of in vitro modulation of leukemic blasts, including CD34+ blasts. III. Correlate response with the presence of other resistance mechanisms, such as atypical MDR and non-P-gp phenotype. IV. Evaluate the toxicity of this treatment in AML patients. V. Study the effect of CYSP on DHAD and VP-16 pharmacokinetics and metabolism and, potentially, on intracellular drug accumulation. OUTLINE: Randomized study. The following acronyms are used: CYSP Cyclosporine, NSC-290193 DHAD Mitoxantrone, NSC-301739 VP-16 Etoposide, NSC-141540 Arm I: 2-Drug Combination Chemotherapy. DHAD; VP-16. Arm II: 2-Drug Combination Chemotherapy with Drug Resistance Inhibition. DHAD; VP-16; with CYSP. PROJECTED ACCRUAL: At least 25 patients/arm will be entered over approximately 3 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.25 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 (AML) in the following categories: Refractory to initial standard therapy consisting of idarubicin/cytarabine and amsacrin/cytarabine (on protocol HOVON 29) First or subsequent relapse following complete response to standard chemotherapy (on protocols HOVON 4/4A or 11 or any other protocol) At least 6 months between mitoxantrone/etoposide and relapse No myelodysplasia PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Not specified Hematopoietic: Not applicable Hepatic: Bilirubin no greater than 2 x normal Alkaline phosphatase no greater than 2 x normal Renal: Creatinine no greater than 1.7 mg/dl (150 micromoles/liter) OR Creatinine clearance at least 60 ml/min Cardiovascular: No uncontrolled hypertension No other severe cardiac disease Pulmonary: No severe pulmonary disease Other: No known intolerance to any study drug No uncontrolled severe infection Not HIV seropositive No severe neurologic or metabolic disease No concomitant malignancy except: Nonmelanomatous skin cancer In situ cervical carcinoma No pregnant women PRIOR CONCURRENT THERAPY: See Disease Characteristics
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 12 locations
Cliniques Universitaires Saint-Luc
Brussels (Bruxelles), BelgiumOpen Cliniques Universitaires Saint-Luc in Google MapsU.Z. Gasthuisberg
Leuven, BelgiumLeyenburg Ziekenhuis
's-Gravenhage (Den Haag, the Hague), NetherlandsAcademisch Ziekenhuis der Vrije Universiteit
Amsterdam, Netherlands