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A Study of Clofarabine for Older Patients With Newly Diagnosed Acute Myelogenous Leukemia (AML) (CLASSIC II)

Primary Purpose

Acute Myelogenous Leukemia, Acute Myeloid Leukemia

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
clofarabine
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, newly Diagnosed AML, Clofarabine, CLASSIC II, CLO243

Eligibility Criteria

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

Inclusion Criteria:

  • Diagnosis of AML (de novo, secondary or with an antecedent hematologic disorder [AHD])
  • Age ≥ 60 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2

  • Presence of at least one adverse prognostic factor: Age ≥ 70 years; or AHD; or ECOG performance status of 2; or Intermediate or unfavorable (i.e., adverse) karyotype defined as any cytogenetic profile except the presence of any of the following:

    • t(8;21)(q22;q22)
    • inv(16)(p13;q22 or t(16;16)(p13;q22)
    • t(15;17)(q22;q12) and variants.
  • Adequate renal and hepatic function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; and Serum creatinine ≤ 1.0 mg/dL; if serum creatinine > 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 60 mL/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation
  • Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥ 40% or left ventricular fractional shortening ≥ 22%

Exclusion Criteria:

  • Diagnosis of acute promyelocytic leukemia
  • Prior treatment with clofarabine
  • Prior treatment for AML or an antecedent hematologic disorder
  • Prior hematopoietic stem cell transplant (HSCT)
  • Prior radiation therapy to the pelvis
  • Investigational agent received within 30 days prior to the first dose of study drug
  • Ongoing uncontrolled systemic infection
  • Diagnosis of another malignancy, unless the patient has been disease-free for at least 5 years following the completion of curative intent therapy with the following exceptions: Patients with treated non-melanoma skin cancer, in-situ carcinoma or cervical intraepithelial neoplasia regardless of 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 based on PSA value are eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed
  • Clinical evidence of central nervous system (CNS) involvement
  • Severe concurrent medical condition or psychiatric disorder that would preclude study participation
  • Positive human immunodeficiency virus (HIV) test

Sites / Locations

  • Mayo Clinical Hospital
  • Arizona Cancer Center
  • USC/Norris Comprehensive Cancer Center and Hospital
  • Scripps Cancer Center
  • Rocky Mountain Cancer Centers
  • Cancer Center of Central Connecticut
  • Emory University School of Medicine
  • Medical College of Georgia
  • Rush University Medical Center
  • Beth Israel Deaconess Medical Center
  • University of Michigan Comprehensive Cancer Center
  • Mount Sinai School of Medicine
  • Oregon Health and Science University
  • Penn State Hershey Medical Center
  • Vanderbilt University Medical Center
  • University of MD Anderson Cancer Center
  • Cancer Care Centers of South Texas
  • University of Utah - Huntsman Cancer Institute
  • Seattle Cancer Care Alliance
  • West Virginia University - HSC

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Clofarabine

Arm Description

Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.

Outcomes

Primary Outcome Measures

Percentage of Participants Achieving Overall Remission (OR) After No More Than Two Cycles (Approximately Month 2)
Best response was assessed by the Independent Response Review Panel(IRRP) after two cycles of treatment. Overall remission(OR) is the sum of complete remission(CR) and complete remission in the absence of platelet recovery(CRp). CR includes normal values for peripheral blood cell counts (absolute neutrophil and platelet) and leukemic blast cells from bone marrow biopsy or aspirate, and absence of extramedullary disease. Partial remission(PR) includes recovery of peripheral blood cells with improved but still abnormal values in leukemic blast cells.

Secondary Outcome Measures

Kaplan Meier Estimate for Duration of Remission (DOR)
DOR was defined as the number of days from achievement of OR as assessed by the Independent Response Review Panel (IRRP) until IRRP-determined disease recurrence or death (any cause), plus 1 day. Participants who initiated alternative antileukemic treatment while in remission were censored on the date the therapy was initiated or on the date of last follow-up.
Kaplan Meier Estimate for Disease-free Survival (DFS)
DFS was defined as the number of days from achievement of IRRP-determined overall response until IRRP-determined disease recurrence or death (any cause), regardless of intervening alternative antileukemic treatment, plus 1 day.
Kaplan Meier Estimates for Overall Survival (OS)
OS was defined as the number of days from first dose of clofarabine until death for all participants, plus 1 day.
Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment and Follow-up Periods
Participants with AEs that occurred during the treatment and follow-up periods. AEs were classified according to severity (graded using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) and relationship to study drug. Treatment emergent is defined as any event that either first presents after baseline or worsens in severity after baseline. NCI Common Terminology Criteria for Severity: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5= Death related to AE
Percentage of Participants Who Died Within Thirty Days of Treatment (30-day Mortality Rate)
Percentage of participants who died within 30 days of the first dose of study drug, regardless of cause.

Full Information

First Posted
September 7, 2006
Last Updated
March 17, 2014
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT00373529
Brief Title
A Study of Clofarabine for Older Patients With Newly Diagnosed Acute Myelogenous Leukemia (AML) (CLASSIC II)
Official Title
A Phase II Study of Single Agent Clofarabine in Previously Untreated Older Adult Patients With Acute Myelogenous Leukemia (AML) for Whom Standard Induction Chemotherapy is Unlikely to be of Benefit
Study Type
Interventional

2. Study Status

Record Verification Date
March 2014
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2010 (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
Clolar (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 lymphoblastic leukemia (ALL) who have had at least 2 prior treatment regimens. This study will evaluate the efficacy of clofarabine in elderly patients with acute myelogenous leukemia (AML) who are unlikely to benefit from treatment with intensive chemotherapy regimens (cytarabine and anthracycline based regimens) used in younger patients with AML.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myelogenous Leukemia, Acute Myeloid Leukemia
Keywords
Acute myelogenous leukemia, Acute myeloid leukemia, newly Diagnosed AML, Clofarabine, CLASSIC II, CLO243

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
116 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Clofarabine
Arm Type
Experimental
Arm Description
Participants received an induction cycle of clofarabine 30 mg/m^2/day intravenous infusion for 5 consecutive days. Participants could then receive up to 5 additional cycles, repeated minimally every 28 days, of clofarabine 20 mg/m^2/day intravenous infusion for 5 consecutive days.
Intervention Type
Drug
Intervention Name(s)
clofarabine
Other Intervention Name(s)
clolar
Intervention Description
Induction cycle 1: cycle 1 of clofarabine 30 mg/m^2/day as a 1-hour intravenous infusion for 5 consecutive days. Reinduction (cycle 2) and/or Consolidation cycles (cycles 2-6): cycles repeated minimally every 28 days, of clofarabine 20 mg/m^2/day as a 1-hour intravenous infusion for 5 consecutive days.
Primary Outcome Measure Information:
Title
Percentage of Participants Achieving Overall Remission (OR) After No More Than Two Cycles (Approximately Month 2)
Description
Best response was assessed by the Independent Response Review Panel(IRRP) after two cycles of treatment. Overall remission(OR) is the sum of complete remission(CR) and complete remission in the absence of platelet recovery(CRp). CR includes normal values for peripheral blood cell counts (absolute neutrophil and platelet) and leukemic blast cells from bone marrow biopsy or aspirate, and absence of extramedullary disease. Partial remission(PR) includes recovery of peripheral blood cells with improved but still abnormal values in leukemic blast cells.
Time Frame
approximately Month 2
Secondary Outcome Measure Information:
Title
Kaplan Meier Estimate for Duration of Remission (DOR)
Description
DOR was defined as the number of days from achievement of OR as assessed by the Independent Response Review Panel (IRRP) until IRRP-determined disease recurrence or death (any cause), plus 1 day. Participants who initiated alternative antileukemic treatment while in remission were censored on the date the therapy was initiated or on the date of last follow-up.
Time Frame
Up to 2 years
Title
Kaplan Meier Estimate for Disease-free Survival (DFS)
Description
DFS was defined as the number of days from achievement of IRRP-determined overall response until IRRP-determined disease recurrence or death (any cause), regardless of intervening alternative antileukemic treatment, plus 1 day.
Time Frame
Up to 2 years
Title
Kaplan Meier Estimates for Overall Survival (OS)
Description
OS was defined as the number of days from first dose of clofarabine until death for all participants, plus 1 day.
Time Frame
Up to 2 years
Title
Overall Participant Counts Summarizing Adverse Events (AEs) During the Treatment and Follow-up Periods
Description
Participants with AEs that occurred during the treatment and follow-up periods. AEs were classified according to severity (graded using National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) and relationship to study drug. Treatment emergent is defined as any event that either first presents after baseline or worsens in severity after baseline. NCI Common Terminology Criteria for Severity: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5= Death related to AE
Time Frame
Up to 2 years
Title
Percentage of Participants Who Died Within Thirty Days of Treatment (30-day Mortality Rate)
Description
Percentage of participants who died within 30 days of the first dose of study drug, regardless of cause.
Time Frame
up to Day 30
Other Pre-specified Outcome Measures:
Title
Number of Participants Achieving Overall Remission After A Maximum of Two Cycles by Subgroup of Baseline Prognostic Factors
Description
The number of participants within each subgroup of baseline prognostic factors of the full analysis set who achieved a best response of either a complete response (CR) or a complete response in the absence of platelet recovery (CRp) as determined by the Independent Response Review Panel following a maximum of two cycles of treatment.
Time Frame
approximately Month 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of AML (de novo, secondary or with an antecedent hematologic disorder [AHD]) Age ≥ 60 years Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Presence of at least one adverse prognostic factor: Age ≥ 70 years; or AHD; or ECOG performance status of 2; or Intermediate or unfavorable (i.e., adverse) karyotype defined as any cytogenetic profile except the presence of any of the following: t(8;21)(q22;q22) inv(16)(p13;q22 or t(16;16)(p13;q22) t(15;17)(q22;q12) and variants. Adequate renal and hepatic function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN); Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; and Serum creatinine ≤ 1.0 mg/dL; if serum creatinine > 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be > 60 mL/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease (MDRD) equation Adequate cardiac function: left ventricular ejection fraction (LVEF) ≥ 40% or left ventricular fractional shortening ≥ 22% Exclusion Criteria: Diagnosis of acute promyelocytic leukemia Prior treatment with clofarabine Prior treatment for AML or an antecedent hematologic disorder Prior hematopoietic stem cell transplant (HSCT) Prior radiation therapy to the pelvis Investigational agent received within 30 days prior to the first dose of study drug Ongoing uncontrolled systemic infection Diagnosis of another malignancy, unless the patient has been disease-free for at least 5 years following the completion of curative intent therapy with the following exceptions: Patients with treated non-melanoma skin cancer, in-situ carcinoma or cervical intraepithelial neoplasia regardless of 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 based on PSA value are eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed Clinical evidence of central nervous system (CNS) involvement Severe concurrent medical condition or psychiatric disorder that would preclude study participation Positive human immunodeficiency virus (HIV) test
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
Phoenix
State/Province
Arizona
Country
United States
Facility Name
Arizona Cancer Center
City
Tucson
State/Province
Arizona
Country
United States
Facility Name
USC/Norris Comprehensive Cancer Center and Hospital
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Scripps Cancer Center
City
San Diego
State/Province
California
Country
United States
Facility Name
Rocky Mountain Cancer Centers
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
Emory University School of Medicine
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Medical College of Georgia
City
Augusta
State/Province
Georgia
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
Country
United States
Facility Name
Penn State Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
University of 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 Utah - Huntsman Cancer Institute
City
Salt Lake City
State/Province
Utah
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
Country
United States
Facility Name
West Virginia University - HSC
City
Morgantown
State/Province
West Virginia
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20026805
Citation
Kantarjian HM, Erba HP, Claxton D, Arellano M, Lyons RM, Kovascovics T, Gabrilove J, Craig M, Douer D, Maris M, Petersdorf S, Shami PJ, Yeager AM, Eckert S, Abichandani R, Faderl S. Phase II study of clofarabine monotherapy in previously untreated older adults with acute myeloid leukemia and unfavorable prognostic factors. J Clin Oncol. 2010 Feb 1;28(4):549-55. doi: 10.1200/JCO.2009.23.3130. Epub 2009 Dec 21.
Results Reference
result

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A Study of Clofarabine for Older Patients With Newly Diagnosed Acute Myelogenous Leukemia (AML) (CLASSIC II)

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