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

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukemia; Acute Myelogenous Leukemia
• Intervention / Treatment: Drug: clofarabine

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States
      • Mayo Clinical Hospital
    • Tucson, Arizona, United States
      • Arizona Cancer Center
  • California
    • Los Angeles, California, United States
      • USC/Norris Comprehensive Cancer Center and Hospital
    • San Diego, California, United States
      • Scripps Cancer Center
  • Colorado
    • Denver, Colorado, United States
      • Rocky Mountain Cancer Centers
  • Connecticut
    • Southington, Connecticut, United States
      • Cancer Center of Central Connecticut
  • Georgia
    • Atlanta, Georgia, United States
      • Emory University School of Medicine
    • Augusta, Georgia, United States
      • Medical College of Georgia
  • Illinois
    • Chicago, Illinois, United States
      • Rush University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States
      • University of Michigan Comprehensive Cancer Center
  • New York
    • New York, New York, United States
      • Mount Sinai School of Medicine
  • Oregon
    • Portland, Oregon, United States
      • Oregon Health and Science University
  • Pennsylvania
    • Hershey, Pennsylvania, United States
      • Penn State Hershey Medical Center
  • Tennessee
    • Nashville, Tennessee, United States
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States
      • University of MD Anderson Cancer Center
    • San Antonio, Texas, United States
      • Cancer Care Centers of South Texas
  • Utah
    • Salt Lake City, Utah, United States
      • University of Utah - Huntsman Cancer Institute
  • Washington
    • Seattle, Washington, United States
      • Seattle Cancer Care Alliance
  • West Virginia
    • Morgantown, West Virginia, United States
      • West Virginia University - HSC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clofarabine; 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.	Drug: clofarabine; 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.; Other Names: clolar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	approximately Month 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years
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.	Up to 2 years
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.	Up to 2 years
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	Up to 2 years
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.	up to Day 30

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Achieving Overall Remission After A Maximum of Two Cycles by Subgroup of Baseline Prognostic Factors	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.	approximately Month 2

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: September 7, 2006
• First Submitted That Met QC Criteria: September 7, 2006
• First Posted (Estimate): September 8, 2006

Study Record Updates

• Last Update Posted (Estimate): April 14, 2014
• Last Update Submitted That Met QC Criteria: March 17, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Acute myelogenous leukemia; Acute myeloid leukemia; Clofarabine; newly Diagnosed AML; CLASSIC II; CLO243
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Clofarabine
• Other Study ID Numbers: CLO24300606