Cytarabine in Combination With Arsenic Trioxide vs. Cytarabine Alone in Elderly Patients With Acute Myeloid Leukemia - Full Text View

Sponsor:	Cephalon
Information provided by:	Cephalon
ClinicalTrials.gov Identifier:	NCT00513305

Purpose

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.

Condition	Intervention	Phase
Acute Myeloid Leukemia	Drug: Arsenic trioxide Drug: Low-dose cytarabine alone	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Acute Myeloid Leukemia Arsenic Leukemia

Drug Information available for: Cytarabine hydrochloride Cytarabine Arsenic trioxide

U.S. FDA Resources

Further study details as provided by Cephalon:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Number of Participants Who Died or Were Censored by 24 Months [ Time Frame: From Baseline through 24 months following Baseline ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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.

Enrollment:	67
Study Start Date:	October 2007
Study Completion Date:	December 2009
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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).

Arms

Assigned Interventions

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).

Eligibility

Ages Eligible for Study:	60 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00513305

Locations

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

Sponsors and Collaborators

Cephalon

More Information

No publications provided

Responsible Party:	Sponsor's Medical Expert, Cephalon
ClinicalTrials.gov Identifier:	NCT00513305 History of Changes
Other Study ID Numbers:	C18477/3059/AM/US-CA
Study First Received:	August 6, 2007
Results First Received:	July 29, 2010
Last Updated:	May 5, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Cephalon:

acute myeloid leukemia, cytarabine, arsenic trioxide.

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Arsenic trioxide
Antimetabolites, Antineoplastic
Antimetabolites

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 12, 2012