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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00373529
First received: September 7, 2006
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Acute Myelogenous Leukemia
Acute Myeloid Leukemia
Drug: clofarabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percentage of Participants Achieving Overall Remission (OR) After No More Than Two Cycles (Approximately Month 2) [ Time Frame: approximately Month 2 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

    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) [ Time Frame: up to Day 30 ] [ Designated as safety issue: Yes ]
    Percentage of participants who died within 30 days of the first dose of study drug, regardless of cause.


Other Outcome Measures:
  • Number of Participants Achieving Overall Remission After A Maximum of Two Cycles by Subgroup of Baseline Prognostic Factors [ Time Frame: approximately Month 2 ] [ Designated as safety issue: No ]
    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.


Enrollment: 116
Study Start Date: October 2006
Study Completion Date: May 2010
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: clolar

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00373529

  Show 20 Study Locations
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

Publications:
Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT00373529     History of Changes
Other Study ID Numbers: CLO24300606
Study First Received: September 7, 2006
Results First Received: February 24, 2011
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Acute myelogenous leukemia
Acute myeloid leukemia
newly Diagnosed AML
Clofarabine
CLASSIC II
CLO243

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Clofarabine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014