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A Phase III Randomized, Double-blind, Controlled Study Comparing Clofarabine and Cytarabine Versus Cytarabine Alone in Adult Patients 55 Years and Older With Acute Myelogenous Leukemia (AML) Who Have Relapsed or Are Refractory After Receiving up to Two Prior Induction Regimens

Phase 3
55 Years
Not Enrolling
Acute Myelogenous Leukemia

Thank you

Trial Information

A Phase III Randomized, Double-blind, Controlled Study Comparing Clofarabine and Cytarabine Versus Cytarabine Alone in Adult Patients 55 Years and Older With Acute Myelogenous Leukemia (AML) Who Have Relapsed or Are Refractory After Receiving up to Two Prior Induction Regimens

After screening and eligibility assessment, patients were randomized (in a 1:1 ratio) to
receive either clofarabine or matching placebo, in addition to cytarabine. Randomization
was stratified by remission status following the first induction regimen (CR1): no
remission [i.e., CR1 = refractory] or remission <6 months vs remission ≥6 months. During
randomization by interactive voice response system (IVRS), there were 10 participants
misclassified to the CR1 <6 months stratum and 12 participants misclassified to CR1 ≥6
months stratum. The error did not affect the participants' treatment, only the
stratification. Due to the misclassification, outcomes that used strata in their analysis
were analyzed twice: once with the 'randomized stratification' which includes the
misclassification and once with the 'calculated stratification' in which participants appear
in the 'correct' strata.

Two clinical study reports were written for this study.

1. Clinical study report dated 7 April 2011 includes the entire treatment period of all
participants plus much of the follow-up. At that time, 33 participants in the
Clofarabine+cytarabine group and 29 participants in the placebo+cytarabine group were
still being follow-up post treatment. Results were reported on in
August 2011. Outcomes that used strata reported the 'calculated strata' on

2. Clinical study report dated 9 July 2012 includes all patient treatment experience plus
all long-term follow-up (a minimum of 2 years from the end of treatment or until the
patient died). The study was completed at that time. Outcomes that used strata
reported the 'randomized strata' on AE records on reflect the final database.

Outcomes that changed between the two clinical study reports due to the additional long-term
follow-up data are reported twice on (once from each clinical study
report) and the appropriate report date is included in the outcome description. Outcomes
from the 9 July 2012 report represent more complete data.

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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Overall Survival - Overall and by Calculated Strata (CSR 7-April-11)

Outcome Description:

Overall survival (OS) for the Full Analysis Set (FAS) and for the 2 calculated strata. OS was defined as the number of months from date of randomization until date of death due to any cause.

Outcome Time Frame:

Day 1 (randomization) up to approximately 4 years

Safety Issue:


Principal Investigator

Medical Monitor

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

August 2006

Completion Date:

January 2012

Related Keywords:

  • Acute Myelogenous Leukemia
  • acute myelogenous leukemia
  • acute myeloid leukemia
  • relapsed AML
  • refractory AML
  • clofarabine
  • cytarabine
  • CLO341
  • clolar
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



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UCLA School of MedicineLos Angeles, California  900121973
Medical University of South CarolinaCharleston, South Carolina  29425-0721
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Louisiana State University Health Science CenterNew Orleans, Louisiana  70112
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Sarah Cannon Research InstituteNashville, Tennessee  37203
University of Kentucky, Markey Cancer CenterLexington, Kentucky  40536-0093
Cancer Care Centers of South TexasSan Antonio, Texas  78229
Stanford Comprehensive Cancer CenterStanford, California  94305
New York Medical CenterNew York, New York  10016
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University of Tennessee Medical CenterKnoxville, Tennessee  37920
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University of Southern California, Kenneth Norris Cancer CenterLos Angeles, California  
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