High Dose Chemotherapy, Peripheral Stem Cell Transplantation, and Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

Sponsor

Roswell Park Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00002945

Collaborator

(none)

Enrollment

Location

176

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Interleukin-2 may stimulate a person's white blood cells to kill leukemia cells.

PURPOSE: Phase III trial to study the effectiveness of high-dose combination chemotherapy, peripheral stem cell transplantation, and interleukin-2 in treating patients who have acute myeloid leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: aldesleukin Biological: filgrastim Drug: cyclophosphamide Drug: cytarabine Drug: etoposide Drug: idarubicin Drug: melphalan Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase 3

Detailed Description

OBJECTIVES:

Determine relapse free survival of patients with previously untreated de novo or secondary acute myeloid leukemia treated with high dose cytarabine and idarubicin induction, high dose etoposide and cyclophosphamide intensification, filgrastim (G-CSF), melphalan, radiotherapy, autologous peripheral blood stem cell (PBSC) transplantation, and interleukin-2.
Correlate remission rate and relapse free survival with multidrug resistance phenotype in patients treated with this regimen.
Determine stem cell content and presence of cells with leukemia specific markers in PBSC harvested following high dose etoposide and cyclophosphamide intensification.
Correlate NK cell expansion (an increase in both proportion and absolute number) during interleukin-2 therapy following autologous PBSC transplantation with disease free survival.

OUTLINE:

Induction

Patients receive cytarabine IV over 1 hour every 12 hours for 6 days and idarubicin IV over 30 minutes following third, fifth, and seventh doses of cytarabine. Beginning 12 hours after the last dose of cytarabine, patients receive filgrastim (G-CSF) subcutaneously (SQ) each day until blood counts recover.

Intensification

Patients receive etoposide IV over 34.3 hours followed 1 hour later by cyclophosphamide IV over 2 hours for 3 days. Beginning 24 hours after the last dose of cyclophosphamide, patients receive G-CSF SQ each day until blood counts recover.

Peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells. Patients receive melphalan IV over 1 hour on day -4 followed by total body irradiation on days -3, -2, and -1. PBSC are reinfused on day 0.

When blood counts recover, patients receive high dose interleukin-2 SQ on days 1-10 followed by low dose interleukin-2 SQ on days 11-13. Interleukin-2 treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with immunologic response to 6 courses of interleukin-2 treatment may continue for 6 additional courses.

PROJECTED ACCRUAL: Approximately 100 patients will be accrued for this study over 5 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

61 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

High-Dose Cytarabine and Idarubicin Induction, High Dose Etoposide and Cyclophosphamide Intensification, Autologous Stem Cell Transplantation and Interleukin-2 Immune Modulation in Previously Untreated De Novo and Secondary Adult Myeloid Leukemia

Study Start Date :

Dec 1, 1996

Actual Primary Completion Date :

Aug 1, 2001

Actual Study Completion Date :

Aug 1, 2011

Outcome Measures

Primary Outcome Measures

To determine the efficacy of 4-6 h and 18-24 h, 20% ALA applications on superficial and nodular epidermally-derived lesions using ca633 nm laser irradiation. [24 hours]
To determine the efficacy of 4-6 h and 18-24 h, 20% ALA applications on superficial and nodular epidermally-derived lesions using ca633 nm laser irradiation.

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically proven de novo or secondary acute myeloid leukemia with a classification of M0-M2 or M4-M7
No classification of M3
No promyelocytic leukemia
Prior medical conditions allowed:
Myelodysplastic syndromes
Aplastic anemia
Paroxysmal nocturnal hemoglobinuria
Myeloproliferative disorders except Philadelphia chromosome positive chronic myelogenous leukemia

PATIENT CHARACTERISTICS:

Age:

Over 25

Performance status:

Not specified

Life expectancy:

At least 4 weeks

Hematopoietic:

Not specified

Hepatic:

Bilirubin no greater than 2 times normal
SGOT no greater than 2 times normal
Alkaline phosphatase no greater than 2 times normal

Renal:

Creatinine no greater than 1.5 times normal

Cardiovascular:

Ejection fraction at least 45%
No severe cardiovascular disease including myocardial infarction within past 6 months, uncontrolled symptomatic congestive heart failure, angina pectoris, or multifocal cardiac arrhythmias