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

Sponsor

University Medical Center Groningen (Other)

Overall Status

Unknown status

CT.gov ID

NCT00002688

Collaborator

(none)

Enrollment

Locations

2.1

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: cyclosporine Drug: etoposide Drug: mitoxantrone hydrochloride	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

Randomized

Primary Purpose:

Treatment

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 Start Date :

Feb 1, 1995

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Cliniques Universitaires Saint-Luc	Brussels (Bruxelles)	Belgium	1200
2	U.Z. Gasthuisberg	Leuven	Belgium	B-3000
3	Leyenburg Ziekenhuis	's-Gravenhage (Den Haag, The Hague)	Netherlands	2545 CH
4	Academisch Ziekenhuis der Vrije Universiteit	Amsterdam	Netherlands	1007 MB
5	Academisch Medisch Centrum	Amsterdam	Netherlands	1105 AZ
6	Academisch Ziekenhuis Groningen	Groningen	Netherlands	9713 EZ
7	Academisch Ziekenhuis Maastricht	Maastricht	Netherlands	6202 AZ
8	University Hospital - Rotterdam Dijkzigt	Rotterdam	Netherlands	3000 CA
9	Academisch Ziekenhuis Utrecht	Utrecht	Netherlands	3508 GA
10	University Hospital	Basel	Switzerland	CH-4031
11	Inselspital, Bern	Bern	Switzerland	CH-3010
12	Universitaetsspital	Zurich	Switzerland	CH-8091