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
18 Years
N/A
Both
Leukemia
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Principal Investigator
Simon Daenen, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
University Medical Centre Groningen
Authority:
United States: Federal Government
Study ID:
CDR0000064413
NCT ID:
NCT00002688
Start Date:
February 1995
Completion Date:
Related Keywords:
- Leukemia
- recurrent adult acute myeloid leukemia
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
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