Cytarabine in Combination With Arsenic Trioxide vs. Cytarabine Alone in Elderly Patients With Acute Myeloid Leukemia

An Open-Label, Randomized Study of Low-Dose Cytarabine in Combination With Arsenic Trioxide Compared With Low-Dose Cytarabine Alone for the Treatment of Elderly Patients With Acute Myeloid Leukemia

The primary objective of this study is to determine whether low-dose cytarabine in combination with arsenic trioxide is more effective than low-dose cytarabine alone in achieving complete remission in elderly patients (≥60 years of age) with acute myeloid leukemia.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Arsenic trioxide; Drug: Low-dose cytarabine alone

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2M9
      • Princess Margaret Hospital
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Cancer Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana Oncology Hematology Consultants
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University
    • New York, New York, United States, 10011
      • St. Vincent's Comprehensive Cancer Center
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Brody School of Medicine
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • San Antonio, Texas, United States, 78229
      • UT Health Science Center

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:

• The patient has confirmed acute myeloid leukemia (AML).
• The patient is unwilling or unable to tolerate conventional induction chemotherapy.
• The patient has no comorbid conditions that would limit life expectancy to less than 3 months.
• Patient must meet specific laboratory parameters for study inclusion.

Exclusion Criteria:

- The patient has had previous cytotoxic chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).

Previous treatment with low-dose cytarabine is not permitted.

• The patient has a QT interval outside of the protocol-specified range.
• The patient has laboratory values outside of protocol-specified ranges.
• The patient is concurrently treated with cytotoxic therapy, radiation, or investigational agents.
• The patient has uncontrolled, severe cardiovascular or pulmonary disease or other uncontrolled medical condition.
• The patient has known central nervous system involvement with AML.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low-dose cytarabine plus arsenic trioxide; Cycle 1 cytarabine 10 mg/m^2 was administered subcutaneously (sc) twice daily (bid) on days 1-14. 0.25 mg/kg arsenic trioxide was administered intravenously (iv) on days 1-5 and days 8-12. Cycle 2 A second identical cycle of cytarabine and arsenic trioxide was given to patients with persistent disease. Patients who achieved complete remission (CR), complete remission with incomplete platelet count recovery (CRp), or partial remission (PR) after 1 or 2 cycles received a 14-day consolidation cycle of cytarabine and arsenic trioxide with the doses and schedule identical to the initial cycle. A recovery period of up to 4 weeks between the attainment of CR, CRp, or PR and the initiation of consolidation treatment was allowed. Patients who completed consolidation treatment started maintenance treatment of arsenic trioxide 0.25 mg/kg iv on days 1 and 4 and cytarabine 10 mg/m^2 sc bid on days 1 through 7 of a 28-day cycle.	Drug: Arsenic trioxide; Arsenic trioxide will be administered intravenously (iv) at a dose of 0.25 mg/kg.; Drug: Low-dose cytarabine alone; Cytarabine will be administered at a dose of 10 mg/m^2 subcutaneously (sc) twice a day (bid).
Active Comparator: Low-dose cytarabine alone; Cytarabine was administered at a dose of 10 mg/m^2 sc bid from days 1-14 of cycle 1. A second identical cycle of cytarabine was given to patients with persistent disease. Patients who achieved a complete remission (CR), complete remission with incomplete platelet count recovery (CRp), or partial remission (PR) after 1 or 2 cycles received a 14-day consolidation cycle of cytarabine with the doses and schedule identical to the initial treatment cycle. Recovery period up to 4 weeks between the attainment of CR, CRp, or PR and the initiation of consolidation treatment was allowed. Patients who completed consolidation treatment started maintenance treatment of cytarabine at 10 mg/m^2 sc bid on days 1-7 of a 28-day cycle. Patients started maintenance treatment within 42 days after platelet count recovery. Maintenance treatment continued for 2 years or until unacceptable toxicity or disease progression.	Drug: Low-dose cytarabine alone; Cytarabine will be administered at a dose of 10 mg/m^2 subcutaneously (sc) twice a day (bid).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in Complete Remission (CR)	The primary efficacy variable was the percentage of subjects in each treatment group who achieved complete remission after treatment with study drug. Complete remission was defined as: 1) Less than 5% blasts in normocellular bone marrow sample. 2) No blasts in bone marrow sample containing Auer rods. 3)Clearance of previous extramedullary disease. 4)Normal values for absolute neutrophil count (at least 1000/microliter), platelet count (at least 100,000/microliter), without platelet transfusions, and in absence of peripheral myeloblasts.	From baseline through Day 70. Assessments were performed on Day 21 in cycle 1, no later than Day 56 of cycle 1 or 2 (if applicable), and no later than Day 70 of cycle 1 or 2 (if applicable) or at any other time at the discretion of the investigator

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Died or Were Censored by 24 Months	This measure (time to death or censor) was defined for all enrolled subjects from the date of randomization until death from any cause. If a subject was not known to have died by the end of the followup period, observation of overall survival was censored on the date the patient was last known to be alive. The number of participants who died or were censored is presented here. (Note: all subjects participating in this study had either died or were censored by 24 months.)	From Baseline through 24 months following Baseline
Proportion of Participants With Relapse-Free Survival (RFS)Using the Kaplan-Meier Estimate	RFS is defined for patients who achieved a complete remission (CR), complete remission with incomplete platelet recovery (CRp), or partial remission(PR), and was measured from the date of attaining CR, CRp, or PR until the date of AML relapse or death from any cause, whichever occurred first. For a patient not known to have relapsed or died by the end of the study followup, observation of relapse free survival was censored on the date of the last followup examination. The Kaplan Meier Estimate of relapse-free survival at Month 3 and Month 6 is presented here.	From Baseline (randomization) through 24 months following Baseline
Number of Participants Who Experienced Early Death	Early death is defined as death from any cause within the first 14 days after start of study drug treatment. The number of patients in each study group who experienced early death is presented here.	14 days from start of study drug treatment
Number of Participants Who Experienced Induction (Thirty-Day) Mortality	The number of subjects who died from any cause within the first 30 days after the start of study drug treatment is presented here.	Up to 30 days following start of study drug treatment
Proportion of Participants Surviving at 6 Months and 12 Months Using the Kaplan Meier Estimate	The duration of overall survival was defined for all patients and was measured from the date of randomization until death from any cause. For a patient who was not known to have died by the end of the follow-up period, observation of overall survival was censored on the date the patient was last known to be alive. The estimate of likelihood of survival at 6 and 12 months after Baseline using the Kaplan Meier Estimate is presented here.	Baseline through 12 months

Collaborators and Investigators

• Sponsor: Cephalon

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): July 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: August 6, 2007
• First Submitted That Met QC Criteria: August 7, 2007
• First Posted (Estimate): August 8, 2007

Study Record Updates

• Last Update Posted (Estimate): August 1, 2012
• Last Update Submitted That Met QC Criteria: July 24, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: acute myeloid leukemia, cytarabine, arsenic trioxide.
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Arsenic Trioxide; Cytarabine
• Other Study ID Numbers: C18477/3059/AM/US-CA