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

Phase 2

Completed

Conditions: Acute Myelogenous Leukemia
Acute Myeloid Leukemia

Interventions: Drug: clofarabine

Registration Number: NCT00373529

Lead Sponsor: Genzyme, a Sanofi Company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 116

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Clofarabine	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Overall Remission (OR) After No More Than Two Cycles (Approximately Month 2)	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

Name	Time	Method
Kaplan Meier Estimate for Duration of Remission (DOR)	Up to 2 years	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)	Up to 2 years	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)	Up to 2 years	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	Up to 2 years	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)	up to Day 30	Percentage of participants who died within 30 days of the first dose of study drug, regardless of cause.

Trial Locations

Locations (20): Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
Penn State Hershey Medical Center
🇺🇸
Hershey, Pennsylvania, United States
West Virginia University - HSC
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Morgantown, West Virginia, United States
Medical College of Georgia
🇺🇸
Augusta, Georgia, United States
Mount Sinai School of Medicine
🇺🇸
New York, New York, United States
Emory University School of Medicine
🇺🇸
Atlanta, Georgia, United States
Cancer Center of Central Connecticut
🇺🇸
Southington, Connecticut, United States
USC/Norris Comprehensive Cancer Center and Hospital
🇺🇸
Los Angeles, California, United States
Mayo Clinical Hospital
🇺🇸
Phoenix, Arizona, United States
Rocky Mountain Cancer Centers
🇺🇸
Denver, Colorado, United States
Scripps Cancer Center
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San Diego, California, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
University of Michigan Comprehensive Cancer Center
🇺🇸
Ann Arbor, Michigan, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
University of MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Cancer Care Centers of South Texas
🇺🇸
San Antonio, Texas, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
University of Utah - Huntsman Cancer Institute
🇺🇸
Salt Lake City, Utah, United States
Seattle Cancer Care Alliance
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Seattle, Washington, United States