Clinical trial NCT00002688: Cyclosporine and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Leukemia
Keywords: recurrent adult acute myeloid leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-07-29
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Some cancers become resistant to chemotherapy drugs. Combining cyclosporine with chemotherapy may prevent resistance to the drugs and allow the cancer cells to be killed.

PURPOSE: Randomized phase II trial to study the effectiveness of adding cyclosporine to combination chemotherapy in treating patients with relapsed or refractory acute myeloid leukemia.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Brussels (Bruxelles)
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: 's-Gravenhage (Den Haag, The Hague)
country: Netherlands
facility: Leyenburg Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Academisch Ziekenhuis der Vrije Universiteit
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Groningen
country: Netherlands
facility: Academisch Ziekenhuis Groningen
city: Maastricht
country: Netherlands
facility: Academisch Ziekenhuis Maastricht
city: Rotterdam
country: Netherlands
facility: University Hospital - Rotterdam Dijkzigt
city: Utrecht
country: Netherlands
facility: Academisch Ziekenhuis Utrecht
city: Basel
country: Switzerland
facility: University Hospital
city: Bern
country: Switzerland
facility: Inselspital, Bern
city: Zurich
country: Switzerland
facility: Universitaetsspital
Study officials:
affiliation: University Medical Center Groningen
name: Simon Daenen, MD, PhD
role: STUDY_CHAIR
References: