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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00373529
• Other study ID #: CLO24300606
• Status: Completed
• Phase: Phase 2
• First received: September 7, 2006
• Last updated: March 17, 2014
• Start date: October 2006
• Est. completion date: May 2010

Study information

• Verified date: March 2014
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: May 2010
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Genzyme, a Sanofi Company

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 a — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes