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

Primary Purpose

Acute Myelogenous Leukemia

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
clofarabine (IV formulation)
placebo
cytarabine
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myelogenous Leukemia focused on measuring acute myelogenous leukemia, acute myeloid leukemia, relapsed AML, refractory AML, clofarabine, cytarabine, CLO341, clolar

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinical Hospital
  • Arizona Cancer Center
  • University of Arkansas for Medical Sciences, Arkansas Cancer Research Center
  • Scripps Cancer Center
  • UCLA School of Medicine
  • University of Southern California, Kenneth Norris Cancer Center
  • Stanford Comprehensive Cancer Center
  • University of Colorado Health Science Center
  • Rocky Mountain Cancer Center
  • Cancer Center of Central Connecticut
  • Northwestern University
  • Rush University Medical Center
  • Evanston Northwestern Healthcare
  • University of Kansas Medical Center
  • University of Kentucky, Markey Cancer Center
  • Louisiana State University Health Science Center
  • Harold Alfond Center for Cancer Care
  • Beth Israel Deaconess Medical Center
  • Josephine Ford Cancer Center
  • Dartmouth Hitchcock Medical Center
  • The Cancer Center at Hackensack University Medical Center
  • Roswell Park Cancer Center
  • Mt. Sinai School of Medicine
  • New York Medical Center
  • Mecklenburg Medical Group
  • Duke University Medical Center
  • Wake Forest University School of Medicine
  • Gabrail Cancer Center
  • University of Oklahoma Health Sciences Center
  • Oregon Health Science University
  • Medical University of South Carolina
  • University of Tennessee Medical Center
  • Sarah Cannon Research Institute
  • Vanderbilt University Medical Center
  • UT Southwestern Medical Center, Simmons Comprehensive Cancer Center
  • MD Anderson Cancer Center
  • Cancer Care Centers of South Texas
  • University of Texas Health Sciences Center
  • University of Utah - Huntsman Cancer Institute
  • West Virginia University Hospitals, Mary Babb Randolph Cancer Center
  • Medical College of Wisconsin
  • Saint John Regional Hospital
  • Juravinski Cancer Center
  • Hopital Maisonneuve-Rosemont
  • Service Maladies du Sang, CHU Angers
  • Hopital Claude Huriez CHRU de Lille
  • Hopital Edouard Herriot
  • Institut Paoli Calmettes
  • Hopital Hotel Dieu
  • Hopital Purpan
  • Medizinische Hochschule Hannover, Zentrum fur Innere Medizin, Abt. Haematologie / Onkologie
  • Medizinische Klinik der Technischen, Universität München
  • Universitatsklinikum Ulm
  • Ospedali Riuniti Bergamo
  • A.O Ospedale Niguarda Ca'Granda
  • N.O. San Gerardo
  • Azienda Ospedaliera "Antonio Cardarelli"

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

clofarabine (IV formulation) and cytarabine

placebo and cytarabine

Arm Description

Participants received clofarabine (40 mg/m^2) administered as a 1-hour infusion followed 3 hours later (from end of infusion) by cytarabine 1 g/m^2 administered as a 2-hour infusion. Participants could receive up to 3 cycles of treatment (induction, re-induction, and consolidation) Complete induction cycle = 5 consecutive days of treatment Re-induction cycle = 5 consecutive days of treatment at the original or modified dose Consolidation cycle = 4 consecutive days of treatment at the original or modified dose

Participants received placebo administered as a 1-hour infusion followed 3 hours later (from end of infusion) by cytarabine 1 g/m^2 administered as a 2-hour infusion. Patients could receive up to 3 cycles of treatment (induction, re-induction, and consolidation)

Outcomes

Primary Outcome Measures

Overall Survival - Overall and by Calculated Strata (CSR 7-April-11)
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.
Overall Survival - Overall and by Randomized Strata (CSR 9-July-12)
Overall survival (OS) for the Full Analysis Set (FAS) and for the 2 randomized strata. OS was defined as the number of months from date of randomization until date of death due to any cause.

Secondary Outcome Measures

Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Percentage of participants whose best response was assessed by the IRRP as complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) using the revised International Working Group for Response Criteria (Cheson 2003). CR is defined on morphologic criteria at a single response assessment: a bone marrow aspirate or biopsy of <5% blasts, with evidence of normal hematopoiesis; absence of Auer rods in the blasts that are present; absence of extramedullary disease; absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; recovery of peripheral counts (platelets ≥100*10^9/L and absolute neutrophil count (ANC) ≥1.0*10^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC <1.0*10^9/L) or thrombocytopenia (platelet count <100*10^9/L).
Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11)
DOR was defined as the time from first CR or CRi to the date of first objective documentation of disease recurrence, initiation of alternative antileukemic therapy [including hematopoietic stem cell transplant] while in remission, or death due to any cause, whichever occurred first. CR is defined on morphologic criteria at a single response assessment: a bone marrow aspirate or biopsy of <5% blasts, with evidence of normal hematopoiesis; absence of Auer rods in the blasts that are present; absence of extramedullary disease; absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; recovery of peripheral counts (platelets ≥100*10^9/L and absolute neutrophil count (ANC) ≥1.0*10^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC <1.0*10^9/L) or thrombocytopenia (platelet count <100*10^9/L).
Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12)
DOR was defined as the time from first CR or CRi to the date of first objective documentation of disease recurrence, initiation of alternative antileukemic therapy [including hematopoietic stem cell transplant] while in remission, or death due to any cause, whichever occurred first. CR is defined on morphologic criteria at a single response assessment: a bone marrow aspirate or biopsy of <5% blasts, with evidence of normal hematopoiesis; absence of Auer rods in the blasts that are present; absence of extramedullary disease; absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; recovery of peripheral counts (platelets ≥100*10^9/L and absolute neutrophil count (ANC) ≥1.0*10^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC <1.0*10^9/L) or thrombocytopenia (platelet count <100*10^9/L).
Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Disease-free survival was defined as the time from first complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first. See Outcome #3 for definition of CR and CRi. Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
Disease-free survival was defined as the time from first complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first. See Outcome #3 for definition of CR and CRi. Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Event-free survival (EFS) was defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
Event-free survival (EFS) was defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Four-month event-free survival (EFS) was defined as achieving an EFS of at least 122 days, where EFS is defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
Four-month event-free survival (EFS) was defined as achieving an EFS of at least 122 days, where EFS is defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Participants With Adverse Events (CSR 7-April-11)
Number of participants with treatment emergent adverse events (TEAEs) or death due to related AE. Related AEs for the combination arm can be related to either clofarabine or cytarabine. Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 = Life Threatening AE, Grade 5 = Death

Full Information

First Posted
April 24, 2006
Last Updated
March 17, 2014
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT00317642
Brief Title
A Study of Clofarabine and Cytarabine for Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)(CLASSIC I)
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 Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
August 2006 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myelogenous Leukemia
Keywords
acute myelogenous leukemia, acute myeloid leukemia, relapsed AML, refractory AML, clofarabine, cytarabine, CLO341, clolar

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
326 (Actual)

8. Arms, Groups, and Interventions

Arm Title
clofarabine (IV formulation) and cytarabine
Arm Type
Experimental
Arm Description
Participants received clofarabine (40 mg/m^2) administered as a 1-hour infusion followed 3 hours later (from end of infusion) by cytarabine 1 g/m^2 administered as a 2-hour infusion. Participants could receive up to 3 cycles of treatment (induction, re-induction, and consolidation) Complete induction cycle = 5 consecutive days of treatment Re-induction cycle = 5 consecutive days of treatment at the original or modified dose Consolidation cycle = 4 consecutive days of treatment at the original or modified dose
Arm Title
placebo and cytarabine
Arm Type
Experimental
Arm Description
Participants received placebo administered as a 1-hour infusion followed 3 hours later (from end of infusion) by cytarabine 1 g/m^2 administered as a 2-hour infusion. Patients could receive up to 3 cycles of treatment (induction, re-induction, and consolidation)
Intervention Type
Drug
Intervention Name(s)
clofarabine (IV formulation)
Other Intervention Name(s)
Clolar®, Evoltra®
Intervention Description
clofarabine (IV formulation) infusion 40mg/m^2 / day up to 3 cycles
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
placebo (sodium Chloride) 1-hour IV infusion
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Description
cytarabine IV infusion 1g/m^2/day for up to 3 cycles
Primary Outcome Measure Information:
Title
Overall Survival - Overall and by Calculated Strata (CSR 7-April-11)
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.
Time Frame
Day 1 (randomization) up to approximately 4 years
Title
Overall Survival - Overall and by Randomized Strata (CSR 9-July-12)
Description
Overall survival (OS) for the Full Analysis Set (FAS) and for the 2 randomized strata. OS was defined as the number of months from date of randomization until date of death due to any cause.
Time Frame
Day 1 (randomization) up to approximately 4 years
Secondary Outcome Measure Information:
Title
Best Response Per Independent Response Review Panel (IRRP) Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Description
Percentage of participants whose best response was assessed by the IRRP as complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) using the revised International Working Group for Response Criteria (Cheson 2003). CR is defined on morphologic criteria at a single response assessment: a bone marrow aspirate or biopsy of <5% blasts, with evidence of normal hematopoiesis; absence of Auer rods in the blasts that are present; absence of extramedullary disease; absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; recovery of peripheral counts (platelets ≥100*10^9/L and absolute neutrophil count (ANC) ≥1.0*10^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC <1.0*10^9/L) or thrombocytopenia (platelet count <100*10^9/L).
Time Frame
Day 12 up to approximately 6 months
Title
Duration of Remission (DOR) Per IRRP Assessment-Overall and by Calculated Strata (CSR 7-April-11)
Description
DOR was defined as the time from first CR or CRi to the date of first objective documentation of disease recurrence, initiation of alternative antileukemic therapy [including hematopoietic stem cell transplant] while in remission, or death due to any cause, whichever occurred first. CR is defined on morphologic criteria at a single response assessment: a bone marrow aspirate or biopsy of <5% blasts, with evidence of normal hematopoiesis; absence of Auer rods in the blasts that are present; absence of extramedullary disease; absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; recovery of peripheral counts (platelets ≥100*10^9/L and absolute neutrophil count (ANC) ≥1.0*10^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC <1.0*10^9/L) or thrombocytopenia (platelet count <100*10^9/L).
Time Frame
Day 12 to approximately 4 years
Title
Duration of Remission (DOR) Per IRRP Assessment-Overall and by Randomized Strata (CSR 9-July-12)
Description
DOR was defined as the time from first CR or CRi to the date of first objective documentation of disease recurrence, initiation of alternative antileukemic therapy [including hematopoietic stem cell transplant] while in remission, or death due to any cause, whichever occurred first. CR is defined on morphologic criteria at a single response assessment: a bone marrow aspirate or biopsy of <5% blasts, with evidence of normal hematopoiesis; absence of Auer rods in the blasts that are present; absence of extramedullary disease; absence of a unique phenotype determined at the pretreatment specimen, as assessed by immunophenotyping; only rare evidence of circulating blasts. If present, evidence of a regenerating bone marrow; recovery of peripheral counts (platelets ≥100*10^9/L and absolute neutrophil count (ANC) ≥1.0*10^9/L). CRi met all criteria for CR except for either residual neutropenia (ANC <1.0*10^9/L) or thrombocytopenia (platelet count <100*10^9/L).
Time Frame
Day 12 to approximately 4 years
Title
Disease-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Description
Disease-free survival was defined as the time from first complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first. See Outcome #3 for definition of CR and CRi. Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time Frame
Day 12 to approximately 4 years
Title
Disease-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
Description
Disease-free survival was defined as the time from first complete remission (CR) or complete remission with incomplete peripheral blood count recovery (CRi) until the date of first objective documentation of disease recurrence or death due to any cause, whichever occurred first. See Outcome #3 for definition of CR and CRi. Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time Frame
Day 12 to approximately 4 years
Title
Event-free Survival by IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Description
Event-free survival (EFS) was defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time Frame
Day 1 (randomization) up to approximately 4 years
Title
Event-free Survival by IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
Description
Event-free survival (EFS) was defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time Frame
Day 1 (randomization) up to approximately 4 years
Title
Four-Month Event-free Survival Per IRRP Assessment - Overall and by Calculated Strata (CSR 7-April-11)
Description
Four-month event-free survival (EFS) was defined as achieving an EFS of at least 122 days, where EFS is defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time Frame
Day 1 (randomization) to Day 122
Title
Four-Month Event-free Survival Per IRRP Assessment - Overall and by Randomized Strata (CSR 9-July-12)
Description
Four-month event-free survival (EFS) was defined as achieving an EFS of at least 122 days, where EFS is defined as the time from randomization to the date of treatment failure, first disease recurrence (for participants who achieved remission), or death due to any cause, whichever occurred first. Treatment Failure - ≥5% leukemic blasts by bone marrow exam, with no evidence of hematologic response (ie, <30% decrease in % leukemic blasts). Disease recurrence - reappearance of leukemic blasts in the peripheral blood, confirmed by ≥5% blasts in the bone marrow, and reappearance or development of pathologically proven extramedullary disease.
Time Frame
Day 1 (randomization) to Day 122
Title
Participants With Adverse Events (CSR 7-April-11)
Description
Number of participants with treatment emergent adverse events (TEAEs) or death due to related AE. Related AEs for the combination arm can be related to either clofarabine or cytarabine. Grade 1 = Mild AE, Grade 2 = Moderate AE, Grade 3 = Severe AE, Grade 4 = Life Threatening AE, Grade 5 = Death
Time Frame
Day 1 up to a maximum of 4 years (includes up to a maximum of 3 cycles of therapy plus 45 days follow up. Related AEs are followed to resolution.)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinical Hospital
City
Scottsdale
State/Province
Arizona
Country
United States
Facility Name
Arizona Cancer Center
City
Tucson
State/Province
Arizona
Country
United States
Facility Name
University of Arkansas for Medical Sciences, Arkansas Cancer Research Center
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
Scripps Cancer Center
City
La Jolla
State/Province
California
Country
United States
Facility Name
UCLA School of Medicine
City
Los Angeles
State/Province
California
Country
United States
Facility Name
University of Southern California, Kenneth Norris Cancer Center
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Stanford Comprehensive Cancer Center
City
Stanford
State/Province
California
Country
United States
Facility Name
University of Colorado Health Science Center
City
Aurora
State/Province
Colorado
Country
United States
Facility Name
Rocky Mountain Cancer Center
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Cancer Center of Central Connecticut
City
Southington
State/Province
Connecticut
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Evanston Northwestern Healthcare
City
Evanston
State/Province
Illinois
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
Country
United States
Facility Name
University of Kentucky, Markey Cancer Center
City
Lexington
State/Province
Kentucky
Country
United States
Facility Name
Louisiana State University Health Science Center
City
Shreveport
State/Province
Louisiana
Country
United States
Facility Name
Harold Alfond Center for Cancer Care
City
Augusta
State/Province
Maine
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Josephine Ford Cancer Center
City
Detroit
State/Province
Michigan
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
Country
United States
Facility Name
The Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
Country
United States
Facility Name
Roswell Park Cancer Center
City
Buffalo
State/Province
New York
Country
United States
Facility Name
Mt. Sinai School of Medicine
City
New York
State/Province
New York
Country
United States
Facility Name
New York Medical Center
City
Valhalla
State/Province
New York
Country
United States
Facility Name
Mecklenburg Medical Group
City
Charlotte
State/Province
North Carolina
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
Wake Forest University School of Medicine
City
Winston-Salem
State/Province
North Carolina
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
Country
United States
Facility Name
University of Oklahoma Health Sciences Center
City
Oklahoma City
State/Province
Oklahoma
Country
United States
Facility Name
Oregon Health Science University
City
Portland
State/Province
Oregon
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
Country
United States
Facility Name
University of Tennessee Medical Center
City
Knoxville
State/Province
Tennessee
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
UT Southwestern Medical Center, Simmons Comprehensive Cancer Center
City
Dallas
State/Province
Texas
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
Country
United States
Facility Name
Cancer Care Centers of South Texas
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
University of Texas Health Sciences Center
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
University of Utah - Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
Country
United States
Facility Name
West Virginia University Hospitals, Mary Babb Randolph Cancer Center
City
Morgantown
State/Province
West Virginia
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
Country
United States
Facility Name
Saint John Regional Hospital
City
Saint John
State/Province
New Brunswick
Country
Canada
Facility Name
Juravinski Cancer Center
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
Hopital Maisonneuve-Rosemont
City
Montreal
State/Province
Quebec
Country
Canada
Facility Name
Service Maladies du Sang, CHU Angers
City
Angers Cedex 01
Country
France
Facility Name
Hopital Claude Huriez CHRU de Lille
City
Lille
Country
France
Facility Name
Hopital Edouard Herriot
City
Lyon
Country
France
Facility Name
Institut Paoli Calmettes
City
Marseille
Country
France
Facility Name
Hopital Hotel Dieu
City
Nantes
Country
France
Facility Name
Hopital Purpan
City
Toulouse
Country
France
Facility Name
Medizinische Hochschule Hannover, Zentrum fur Innere Medizin, Abt. Haematologie / Onkologie
City
Hannover
Country
Germany
Facility Name
Medizinische Klinik der Technischen, Universität München
City
Munich
Country
Germany
Facility Name
Universitatsklinikum Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Ospedali Riuniti Bergamo
City
Bergamo
Country
Italy
Facility Name
A.O Ospedale Niguarda Ca'Granda
City
Milano
Country
Italy
Facility Name
N.O. San Gerardo
City
Monza
Country
Italy
Facility Name
Azienda Ospedaliera "Antonio Cardarelli"
City
Napoli
Country
Italy

12. IPD Sharing Statement

Citations:
Citation
Clofarabine + Ara-c improves response rates and event-free survival, not overall survival, in older patients with relapsed/refractory AML compared to Ara-c alone: Updated CLASSIC I study results. H.M. Kantarjian, M. Wetzler, D. Rizzieri, G. J. Schiller, M. H. Jagasia, R. K. Stuart, S. Ganguly, D. Avigan, M. Craig, R. Collins, M. B. Maris, T. Kovacsovics, S. Goldberg, K. Seiter, P. Hari, J. Greiner, N. Vey, C. Recher, F. Ravandi, E.S. Wang, S. Eckert, D. Huebner and S. Faderl. Haematologica - 16th Congress of EHA Abstracts. 2011; 96(S2): 196.
Results Reference
result
Citation
Clofarabine plus cytarabine compared to cytarabine alone in older patients with relapsed or refractory (R/R) acute myelogenous leukemia (AML): Results from the phase III CLASSIC 1 trial. S. Faderl, M. Wetzler, D. Rizzieri, G. J. Schiller, M. H. Jagasia, R. K. Stuart, S. Ganguly, D. Avigan, M. Craig, R. Collins, M. B. Maris, T. Kovacsovics, S. Goldberg, K. Seiter, P. Hari, F. Ravandi, E. S. Wang, S. Eckert, D. Huebner, and H. Kantarjian JCO - ASCO Meeting Abstracts. 2011; 29:6503.
Results Reference
result
PubMed Identifier
22585697
Citation
Faderl S, Wetzler M, Rizzieri D, Schiller G, Jagasia M, Stuart R, Ganguly S, Avigan D, Craig M, Collins R, Maris M, Kovacsovics T, Goldberg S, Seiter K, Hari P, Greiner J, Vey N, Recher C, Ravandi F, Wang ES, Vasconcelles M, Huebner D, Kantarjian HM. Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol. 2012 Jul 10;30(20):2492-9. doi: 10.1200/JCO.2011.37.9743. Epub 2012 May 14.
Results Reference
result
Citation
Ganguly S, Kantarjian HM, Wetzler M, Rizzieri D, Schiller G, Jagasia M, et al. Subsequent hematopoietic stem cell transplantation (HSCT) associated with longer survival in patients with relapsed/refractory (R/R) acute myelogenous leukemia (AML) after Clo+Ara-C or Ara-C alone: a landmark analysis from the CLASSIC I trial. Biol Blood Marrow Transplant 2012;18(2Suppl):S211-S212.
Results Reference
result
Citation
Ganguly S, Kantarjian HM, Wetzler M, Rizzieri D, Schiller G, Jagasia M, et al. Subsequent HSCT in the CLASSIC I Study Associated with Longer Survival in Patients With Relapsed/Refractory AML After Clo+Ara-C Or Ara-C Alone: A Landmark Analysis. Haematologica - 17th Congress of EHA Abstracts. 2012; 97(s1):32
Results Reference
result

Learn more about this trial

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

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