Clofarabine (injection) is approved by the Food and Drug Administration (FDA) for the
treatment of pediatric patients 1 to 21 years old with relapsed acute or refractory
lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens.
There is no recommended standard treatment for relapsed or refractory acute myelogenous
leukemia in older patients. Cytarabine is the most commonly used drug to treat these
patients. This study will determine if there is benefit by combining clofarabine with
cytarabine. Patients will be randomized to receive up to 3 cycles of treatment with either
placebo in combination with cytarabine or clofarabine in combination with cytarabine.
Randomization was stratified by remission status following the first induction regimen (no
remission [i. e., CR1 = refractory] or remission <6 months vs CR1 = remission ≥6 months).
CR1 is defined as remission after first pre-study induction regimen. The safety and
tolerability of clofarabine in combination with cytarabine and cytarabine alone will be
monitored throughout the study.
Minimum age: 55 Years.
Maximum age: N/A.
Gender(s): Both.
Inclusion Criteria:
- Have a diagnosis of Acute Myelogenous Leukemia (AML) according to World Health
Organization (WHO) classification
- Relapsed after receiving up to 2 prior induction regimens (i. e. first or second
relapse)or are refractory to not more than one prior combination chemotherapy
induction regimen
- Be ≥ 55 years of age
- Have an Eastern Cooperative Oncology Group (ECOG) score of 0-2
- Be able to comply with study procedures and follow-up examinations
- Be nonfertile or agree to use birth control during the study through the end of
treatment visit and for at least 90 days after the last dose of study drug
- Have adequate liver and renal function as indicated by certain laboratory values
Exclusion Criteria:
- Received previous treatment with clofarabine
- Received bolus, intermediate or high-dose cytarabine as induction therapy unless
certain remission criteria are met
- Have received a hematopoietic stem cell transplant (HSCT) within the previous 3
months
- Have moderate or severe graft versus host disease (GVHD), whether acute or chronic
- Are receiving any other chemotherapy or investigational therapy. Patients must have
been off prior AML therapy for at least 2-6 weeks prior to entering study.
- Have a psychiatric disorder that would interfere with consent, study participation,
or follow-up
- Have an active, uncontrolled infection
- Have any other severe concurrent disease, or have a history of serious organ
dysfunction or disease involving the heart, kidney, liver, or other organ system
- Have been diagnosed with another malignancy, unless disease-free for at least 5
years; patients with treated nonmelanoma skin cancer, in situ carcinoma, or cervical
intraepithelial neoplasia, regardless of the disease-free duration, are eligible for
this study if definitive treatment for the condition has been completed; patients
with organ-confined prostate cancer with no evidence of recurrent or progressive
disease are eligible if hormonal therapy has been initiated or the malignancy has
been surgically removed.
- Have clinical evidence suggestive of central nervous system (CNS) involvement with
leukemia unless lumbar puncture confirms absence of leukemic blasts in the
cerebrospinal fluid(CSF)
- Known HIV positivity
- Are pregnant or lactating
Service Maladies du Sang, CHU Angers, Angers Cedex 01, France
Hopital Claude Huriez CHRU de Lille, Lille, France
Hopital Edouard Herriot, Lyon, France
Institut Paoli Calmettes, Marseille, France
Hopital Hotel Dieu, Nantes, France
Hopital Purpan, Toulouse, France
Medizinische Hochschule Hannover, Zentrum fur Innere Medizin, Abt. Haematologie / Onkologie, Hannover, Germany
Medizinische Klinik der Technischen, Universität München, Munich, Germany
Universitatsklinikum Ulm, Ulm 89081, Germany
Ospedali Riuniti Bergamo, Bergamo, Italy
A.O Ospedale Niguarda Ca'Granda, Milano, Italy
N.O. San Gerardo, Monza, Italy
Azienda Ospedaliera "Antonio Cardarelli", Napoli, Italy
Mayo Clinical Hospital, Scottsdale, Arizona, United States
Arizona Cancer Center, Tucson, Arizona, United States
University of Arkansas for Medical Sciences, Arkansas Cancer Research Center, Little Rock, Arkansas, United States
Scripps Cancer Center, La Jolla, California, United States
UCLA School of Medicine, Los Angeles, California, United States
University of Southern California, Kenneth Norris Cancer Center, Los Angeles, California, United States
Stanford Comprehensive Cancer Center, Stanford, California, United States
University of Colorado Health Science Center, Aurora, Colorado, United States
Rocky Mountain Cancer Center, Denver, Colorado, United States
Cancer Center of Central Connecticut, Southington, Connecticut, United States
Northwestern University, Chicago, Illinois, United States
Rush University Medical Center, Chicago, Illinois, United States
Evanston Northwestern Healthcare, Evanston, Illinois, United States
University of Kansas Medical Center, Kansas City, Kansas, United States
University of Kentucky, Markey Cancer Center, Lexington, Kentucky, United States
Louisiana State University Health Science Center, Shreveport, Louisiana, United States
Harold Alfond Center for Cancer Care, Augusta, Maine, United States
Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
Josephine Ford Cancer Center, Detroit, Michigan, United States
Saint John Regional Hospital, Saint John, New Brunswick, Canada
Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, United States
The Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States
Roswell Park Cancer Center, Buffalo, New York, United States
Mt. Sinai School of Medicine, New York, New York, United States
New York Medical Center, Valhalla, New York, United States
Mecklenburg Medical Group, Charlotte, North Carolina, United States
Duke University Medical Center, Durham, North Carolina, United States
Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
Gabrail Cancer Center, Canton, Ohio, United States
University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
Juravinski Cancer Center, Hamilton, Ontario, Canada
Oregon Health Science University, Portland, Oregon, United States
Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada
Medical University of South Carolina, Charleston, South Carolina, United States
University of Tennessee Medical Center, Knoxville, Tennessee, United States
Sarah Cannon Research Institute, Nashville, Tennessee, United States
Vanderbilt University Medical Center, Nashville, Tennessee, United States
UT Southwestern Medical Center, Simmons Comprehensive Cancer Center, Dallas, Texas, United States
MD Anderson Cancer Center, Houston, Texas, United States
Cancer Care Centers of South Texas, San Antonio, Texas, United States
University of Texas Health Sciences Center, San Antonio, Texas, United States
University of Utah - Huntsman Cancer Institute, Salt Lake City, Utah, United States
West Virginia University Hospitals, Mary Babb Randolph Cancer Center, Morgantown, West Virginia, United States
Medical College of Wisconsin, Milwaukee, Wisconsin, United States