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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Acute Myelogenous Leukemia, Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: clofarabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clofarabine<br>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<br>* 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.<br>* Other names: clolar;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myelogenous leukemia, Acute myeloid leukemia, newly Diagnosed AML, Clofarabine, CLASSIC II, CLO243