Cyclosporine and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00002688
• Other study ID #: CDR0000064413
• Secondary ID: DUT-KWF-CKVO-941
• Status: Active, not recruiting
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: December 18, 2013
• Start date: February 1995

Study information

• Verified date: May 2007
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 25
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid, Acute

Intervention

Drug:
• cyclosporine

• etoposide

• mitoxantrone hydrochloride

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels (Bruxelles)
Belgium	U.Z. Gasthuisberg	Leuven
Netherlands	Leyenburg Ziekenhuis	's-Gravenhage (Den Haag, The Hague)
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	Academisch Ziekenhuis der Vrije Universiteit	Amsterdam
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Netherlands	Academisch Ziekenhuis Maastricht	Maastricht
Netherlands	University Hospital - Rotterdam Dijkzigt	Rotterdam
Netherlands	Academisch Ziekenhuis Utrecht	Utrecht
Switzerland	University Hospital	Basel
Switzerland	Inselspital, Bern	Bern
Switzerland	Universitaetsspital	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Countries where clinical trial is conducted

Belgium,  Netherlands,  Switzerland,