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

Sponsors and Collaborators:	Roswell Park Cancer Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002945

Purpose

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	Intervention	Phase
Leukemia	Drug: aldesleukin Drug: cyclophosphamide Drug: cytarabine Drug: etoposide Drug: filgrastim Drug: idarubicin Drug: melphalan Procedure: peripheral blood stem cell transplantation Procedure: radiation therapy	Phase III

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Cyclophosphamide Filgrastim Cytarabine Cytarabine hydrochloride Etoposide Idarubicin Idarubicin hydrochloride Melphalan Aldesleukin Etoposide phosphate Melphalan hydrochloride Sarcolysin Interleukin-2

U.S. FDA Resources

Study Type:	Interventional
Study Design:	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

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	100
Study Start Date:	December 1996

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.

Eligibility

Ages Eligible for Study:	25 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002945

Locations

United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001

Sponsors and Collaborators

Roswell Park Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Maria R. Baer, MD

Roswell Park Cancer Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000065406, RPCI-DS-96-48, NCI-G97-1152
Study First Received:	November 1, 1999
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00002945
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

untreated adult acute myeloid leukemia
adult acute monoblastic leukemia and acute monocytic leukemia (M5)
adult acute erythroid leukemia (M6)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)

adult acute myelomonocytic leukemia (M4)
adult acute megakaryoblastic leukemia (M7)
secondary acute myeloid leukemia
adult acute minimally differentiated myeloid leukemia (M0)

Study placed in the following topic categories:

Leukemia, Monocytic, Acute
Melphalan
Acute myelogenous leukemia
Acute myelomonocytic leukemia
Cyclophosphamide
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Di Guglielmo's syndrome
Etoposide phosphate
Leukemia, Myelomonocytic, Acute
Leukemia

Idarubicin
Aldesleukin
Leukemia, Erythroblastic, Acute
Interleukin-2
Neoplasm Metastasis
Acute erythroblastic leukemia
Acute myeloid leukemia, adult
Etoposide
Acute myelocytic leukemia
Acute monoblastic leukemia
Cytarabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Anti-Retroviral Agents
Sensory System Agents
Therapeutic Uses
Analgesics
Alkylating Agents

Neoplasms by Histologic Type
Anti-HIV Agents
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Analgesics, Non-Narcotic
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Peripheral Nervous System Agents
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 14, 2009