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

• ClinicalTrials.gov Identifier: NCT00513305
• Recruitment Status: Terminated
• First Posted: August 8, 2007
• Results First Posted: March 29, 2011
• Last Update Posted: August 1, 2012
• Sponsor: Cephalon
• Information provided by (Responsible Party): Teva Pharmaceutical Industries ( Cephalon )

Tracking Information

• First Submitted Date: August 6, 2007
• First Posted Date: August 8, 2007
• Results First Submitted Date: July 29, 2010
• Results First Posted Date: March 29, 2011
• Last Update Posted Date: August 1, 2012
• Study Start Date: October 2007
• Actual Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 28, 2011)

Percentage of Participants in Complete Remission (CR) [ Time Frame: 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 ]

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.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: March 28, 2011)

• Number of Participants Who Died or Were Censored by 24 Months [ Time Frame: From Baseline through 24 months following Baseline ]
  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.)
• Proportion of Participants With Relapse-Free Survival (RFS)Using the Kaplan-Meier Estimate [ Time Frame: From Baseline (randomization) through 24 months following Baseline ]
  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.
• Number of Participants Who Experienced Early Death [ Time Frame: 14 days from start of study drug treatment ]
  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.
• Number of Participants Who Experienced Induction (Thirty-Day) Mortality [ Time Frame: Up to 30 days following start of study drug treatment ]
  The number of subjects who died from any cause within the first 30 days after the start of study drug treatment is presented here.
• Proportion of Participants Surviving at 6 Months and 12 Months Using the Kaplan Meier Estimate [ Time Frame: Baseline through 12 months ]
  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.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cytarabine in Combination With Arsenic Trioxide vs. Cytarabine Alone in Elderly Patients With Acute Myeloid Leukemia
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia

Intervention

• 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).

Study Arms

• 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.
  Interventions:

  • Drug: Arsenic trioxide
  • Drug: Low-dose cytarabine alone
• 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.
  Intervention: Drug: Low-dose cytarabine alone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 30, 2009): 67
• Original Estimated Enrollment (submitted: August 7, 2007): 210
• Actual Study Completion Date: December 2009
• Actual Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT00513305
• Other Study ID Numbers: C18477/3059/AM/US-CA
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Teva Pharmaceutical Industries ( Cephalon )
• Study Sponsor: Cephalon
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Teva Pharmaceutical Industries
• Verification Date: July 2012