S0301 Cyclosporine, Daunorubicin, and Cytarabine in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

A Phase II Study Of Induction With Daunorubicin, Cytarabine, And Cyclosporine All By Continuous IV Infusion For Previously Untreated Non-M3 Acute Myeloid Leukemia (AML) In Patients Of Age 56 Or Older

RATIONALE: Drugs used in chemotherapy, such as cyclosporine, daunorubicin, and cytarabine, use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving cyclosporine together with daunorubicin and cytarabine works in treating older patients with untreated acute myeloid leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Biological: filgrastim; Biological: sargramostim; Drug: cyclosporine; Drug: cytarabine; Drug: daunorubicin hydrochloride

Detailed Description

OBJECTIVES:

• Determine the safety and efficacy of cyclosporine, daunorubicin, and cytarabine in older patients with previously untreated acute myeloid leukemia.
• Determine the frequency and severity of toxic effects of this regimen in these patients.
• Determine, preliminarily, the frequency and prognostic significance of functional and phenotypic P-glycoprotein expression and cytogenetics in patients treated with this regimen.
• Determine, preliminarily, the pharmacokinetic characteristics of this regimen in these patients.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive cyclosporine IV and daunorubicin IV continuously on days 1-3 and cytarabine IV continuously on days 1-7. Patients who achieve complete response (CR) after chemotherapy receive filgrastim (G-CSF) or sargramostim (GM-CSF) IV or subcutaneously beginning on day 15 or 20 and continuing until blood counts recover. Patients who maintain CR after 2 courses of induction therapy proceed to consolidation therapy.
• Consolidation therapy: Patients receive treatment as in induction therapy with cyclosporine and daunorubicin on days 1-2 and cytarabine on days 1-5. Patients achieving CR receive an additional course of chemotherapy beginning at least 14 days after completion of the first course of cytarabine.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 25-64 patients will be accrued for this study within 13 months.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36652-2144
      • Mobile Infirmary Medical Center
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center at University of Arizona Health Sciences Center
  • California
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
    • Redding, California, United States, 96049
      • Mercy Regional Cancer Center at Mercy Medical Center
  • Idaho
    • Boise, Idaho, United States, 83712
      • St. Luke's Mountain States Tumor Institute - Boise
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Hospital at Saint Anthony's Health Center
    • Mt. Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - Salina
    • Salina, Kansas, United States, 67401
      • Tammy Walker Cancer Center at Salina Regional Health Center
    • Topeka, Kansas, United States, 66606
      • St. Francis Comprehensive Cancer Center
    • Topeka, Kansas, United States, 66604
      • Stormont-Vail Cancer Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
    • Wichita, Kansas, United States, 67203
      • Associates in Womens Health, PA - North Review
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Louisiana
    • Alexandria, Louisiana, United States, 71315-3198
      • Tulane Cancer Center
    • Monroe, Louisiana, United States, 71210
      • Louisiana State University Health Sciences Center - Monroe
    • Shreveport, Louisiana, United States, 71130-3932
      • Feist-Weiller Cancer Center at Louisiana State University Health Sciences
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0942
      • University of Michigan Comprehensive Cancer Center
    • Battle Creek, Michigan, United States, 49017
      • Battle Creek Health System Cancer Care Center
    • Bay City, Michigan, United States, 48708
      • Bay Regional Medical Center
    • Big Rapids, Michigan, United States, 49307
      • Mecosta County Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Health Care
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Hospital - Butterworth Campus
    • Grand Rapids, Michigan, United States, 49506
      • Metropolitan Hospital
    • Holland, Michigan, United States, 49423
      • Holland Community Hospital
    • Muskegon, Michigan, United States, 49443
      • Hackley Hospital
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute at Providence Hospital - Southfield Campus
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Cape Girardeau, Missouri, United States, 63701
      • Saint Francis Medical Center
    • Gape Girardeau, Missouri, United States, 63701
      • Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
    • Saint Louis, Missouri, United States, 63141
      • David C. Pratt Cancer Center at St. John's Mercy
    • St. Louis, Missouri, United States, 63141
      • CCOP - St. Louis-Cape Girardeau
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare
    • Billings, Montana, United States, 59107-7000
      • Deaconess Billings Clinic - Downtown
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • St. James Community Hospital
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Big Sky Oncology
    • Great Falls, Montana, United States, 59405
      • Sletten Regional Cancer Institute at Benefis Healthcare
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology
    • Missoula, Montana, United States, 59801
      • Community Medical Center
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
    • Missoula, Montana, United States, 59804
      • Clinic of Dr. Judy L. Schmidt
  • New York
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14620
      • Highland Hospital of Rochester
    • Rochester, New York, United States, 14623
      • Interlakes Oncology/Hematology PC
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Rutherfordton, North Carolina, United States, 28139
      • Rutherford Hospital
    • Wilson, North Carolina, United States, 27893-3428
      • Wilson Medical Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Columbus, Ohio, United States, 43214-3998
      • Riverside Methodist Hospital Cancer Care
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health - West Hospital
    • Columbus, Ohio, United States, 43215
      • CCOP - Columbus
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital at Ohio Health
    • Columbus, Ohio, United States, 43215
      • Grant Riverside Cancer Services
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Marietta, Ohio, United States, 45750
      • Strecker Cancer Center at Marietta Memorial Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Cancer Care Program at Licking Memorial Hospital
    • Springfield, Ohio, United States, 45505
      • Community Hospital of Springfield and Clark County
    • Springfield, Ohio, United States, 45504
      • Mercy Medical Center
    • Westerville, Ohio, United States, 43081
      • Mount Carmel Cancer Services at Mount Carmel St. Ann's Hospital
    • Youngstown, Ohio, United States, 44501
      • Tod Children's Hospital - Forum Health
    • Zanesville, Ohio, United States, 43701
      • Genesis - Good Samaritan Hospital
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
    • Spartanburg, South Carolina, United States, 29303
      • CCOP - Upstate Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
  • Texas
    • Temple, Texas, United States, 76508
      • CCOP - Scott and White Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute at University of Utah
  • Washington
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 56 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Morphologically confirmed acute myeloid leukemia (AML)

  • Differential diagnosis of AML based on FAB classification system

    • M0-M7 (No M3)
• No blastic transformation of chronic myelogenous leukemia
• Must be currently registered on protocols SWOG-9007 and SWOG-S9910

PATIENT CHARACTERISTICS:

Age

• 56 and over

Performance status

• Zubrod 0-3 (for patients 56 to 60 years of age) OR
• Zubrod 0-2 (for patients 61 to 70 years of age) OR
• Zubrod 0-1 (for patients 71 years of age and over)

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin no greater than 2 times upper limit of normal (ULN) unless elevated unconjugated hyperbilirubinemia is secondary to Gilbert's syndrome or hemolysis and not to liver dysfunction
• AST and/or ALT no greater than 4 times ULN

Renal

• Creatinine no greater than 1.5 times ULN AND/OR
• Creatinine clearance greater than 40 mL/min

Cardiovascular

• Left ventricular function normal
• Ejection fraction at least 50% by MUGA or echocardiogram
• No unstable cardiac arrhythmias
• No unstable angina

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer that is currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent pegfilgrastim

Chemotherapy

• At least 30 days since prior low-dose cytarabine (less than 100 mg/m^2/day) for myelodysplastic syndromes and recovered
• Prior hydroxyurea to control high cell counts allowed
• No prior systemic chemotherapy for acute leukemia
• Concurrent single-dose intrathecal chemotherapy allowed

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Complete remission (CR)	After induction therapy is completed

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Thomas R. Chauncey, MD, PhD, VA Puget Sound Health Care System; Principal Investigator: Cheryl L. Willman, MD, University of New Mexico Cancer Center; Principal Investigator: Marilyn L. Slovak, PhD, City of Hope Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: August 6, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (Estimate): August 7, 2003

Study Record Updates

• Last Update Posted (Estimate): March 6, 2015
• Last Update Submitted That Met QC Criteria: March 5, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); untreated adult acute myeloid leukemia; adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Antibiotics, Antineoplastic; Antifungal Agents; Calcineurin Inhibitors; Cytarabine; Daunorubicin; Sargramostim; Cyclosporine; Cyclosporins
• Other Study ID Numbers: S0301 (Other Identifier: SWOG); U10CA032102 (U.S. NIH Grant/Contract)