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A Study of Clofarabine and Cytarabine for Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)(CLASSIC I)

Information source: Sanofi
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute Myelogenous Leukemia

Intervention: clofarabine (IV formulation) (Drug); placebo (Drug); cytarabine (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Genzyme, a Sanofi Company

Official(s) and/or principal investigator(s):
Medical Monitor, Study Director, Affiliation: Genzyme, a Sanofi Company

Summary

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.

Clinical Details

Official title: 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

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

Primary outcome:

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

Overall Survival - Overall and by Randomized Strata (CSR 9-July-12)

Secondary outcome:

Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11)

Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11)

Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12)

Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)

Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)

Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)

Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)

Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)

Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)

Participants With Adverse Events (CSR 7-April-11)

Detailed description: 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 clinicaltrials. gov in August 2011. Outcomes that used strata reported the 'calculated strata' on clinicaltrials. gov. 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 clinicaltrials. gov. AE records on clinicaltrials. gov 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 clinicaltrials. gov (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.

Eligibility

Minimum age: 55 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Locations and Contacts

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

Additional Information

Starting date: August 2006
Last updated: March 17, 2014

Page last updated: August 23, 2015

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