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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002945
• Other study ID #: CDR0000065406
• Secondary ID: RPCI-DS-96-48
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: April 12, 2012
• Start date: December 1996
• Est. completion date: August 2011

Study information

• Verified date: April 2012
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: August 2011
• Est. primary completion date: August 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years and older

Eligibility

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

Other:

• No uncontrolled diabetes mellitus

• No other active malignancy

• No hypersensitivity to E. coli derived drug preparations

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy for acute leukemia except hydroxyurea

• Prior chemotherapy allowed for other malignancy or other medical condition

Endocrine therapy:

• Not specified

Radiotherapy:

• Prior radiotherapy allowed for other malignancy or other medical condition

Surgery:

• Not specified

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• aldesleukin
IV
• filgrastim
IV

Drug:
• cyclophosphamide
IV
• cytarabine
IV
• etoposide
IV
• idarubicin
IV
• melphalan
IV

Procedure:
• peripheral blood stem cell transplantation
IV

Radiation:
• radiation therapy
delivered to the cancer cells

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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	Yes