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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00002945
First received: November 1, 1999
Last updated: April 12, 2012
Last verified: April 2012
  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
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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

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. [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 61
Study Start Date: December 1996
Study Completion Date: August 2011
Primary Completion Date: August 2001 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: aldesleukin
    IV
    Biological: filgrastim
    IV
    Drug: cyclophosphamide
    IV
    Drug: cytarabine
    IV
    Drug: etoposide
    IV
    Drug: idarubicin
    IV
    Drug: melphalan
    IV
    Procedure: peripheral blood stem cell transplantation
    IV
    Radiation: radiation therapy
    delivered to the cancer cells
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Meir Wetzler, MD Roswell Park Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00002945     History of Changes
Other Study ID Numbers: CDR0000065406, RPCI-DS-96-48
Study First Received: November 1, 1999
Last Updated: April 12, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Roswell Park Cancer Institute:
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)

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Cytarabine
Etoposide
Idarubicin
Interleukin-2
Alkylating Agents
Analgesics
Analgesics, Non-Narcotic
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Antiviral Agents
Central Nervous System Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Peripheral Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 21, 2014