Trial Outcomes & Findings for Cytarabine in Combination With Arsenic Trioxide vs. Cytarabine Alone in Elderly Patients With Acute Myeloid Leukemia (NCT NCT00513305)

Last Updated: 2012-08-01

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

67 participants

Primary outcome timeframe

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

Results posted on

2012-08-01

Participant Flow

Seven centers in the United States and one center in Canada. First patient enrolled 12 October 2007; last patient completed protocol-specified treatment 5 July 2009; last patient completed survival follow-up contact 16 December 2009.

Participant milestones

Participant milestones
Measure	Low-dose Cytarabine Plus Arsenic Trioxide Cycle 1. 10 mg/m\^2 cytarabine 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 identified from a bone marrow sample taken on day 21 of cycle 1. 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.	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 treatment was given to patients with persistent disease identified from a bone marrow sample taken on day 21 of cycle 1. 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. 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 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.
Overall Study STARTED	33	34
Overall Study COMPLETED	5	7
Overall Study NOT COMPLETED	28	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Low-dose Cytarabine Plus Arsenic Trioxide Cycle 1. 10 mg/m\^2 cytarabine 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 identified from a bone marrow sample taken on day 21 of cycle 1. 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.	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 treatment was given to patients with persistent disease identified from a bone marrow sample taken on day 21 of cycle 1. 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. 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 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.
Overall Study Adverse Event	6	2
Overall Study Death (through Consolidation Treatment)	2	2
Overall Study Lack of Efficacy	8	13
Overall Study Withdrawal by Subject	1	2
Overall Study Disease progression	8	5
Overall Study Eligible for stem cell transplant	1	0
Overall Study Hematologic counts did not recover	1	0
Overall Study Physician Decision	1	0
Overall Study Persistent hypocellularity	0	1
Overall Study Sponsor Decision	0	2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low-dose Cytarabine Plus Arsenic Trioxide n=33 Participants Cycle 1. 10 mg/m\^2 cytarabine 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 identified from a bone marrow sample taken on day 21 of cycle 1. 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.	Low-dose Cytarabine Alone n=34 Participants 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 treatment was given to patients with persistent disease identified from a bone marrow sample taken on day 21 of cycle 1. 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. 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 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.	Total n=67 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Age, Categorical >=65 years	24 Participants n=5 Participants	27 Participants n=7 Participants	51 Participants n=5 Participants
Age Continuous	70.9 years STANDARD_DEVIATION 7.1 • n=5 Participants	71.5 years STANDARD_DEVIATION 6.8 • n=7 Participants	71.2 years STANDARD_DEVIATION 6.9 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	17 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants	17 Participants n=7 Participants	34 Participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants	32 participants n=7 Participants	64 participants n=5 Participants
Region of Enrollment Canada	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: Intention to treat (ITT) Analysis Set

Outcome measures

Outcome measures
Measure	Low-dose Cytarabine Plus Arsenic Trioxide n=33 Participants Cycle 1. 10 mg/m\^2 cytarabine 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 identified from a bone marrow sample taken on day 21 of cycle 1. 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.	Low-dose Cytarabine Alone n=34 Participants 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 treatment was given to patients with persistent disease identified from a bone marrow sample taken on day 21 of cycle 1. 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. 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 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.
Percentage of Participants in Complete Remission (CR)	15.2 Percentage of participants in CR Interval 0.051 to 0.319	8.8 Percentage of participants in CR Interval 0.019 to 0.0237

SECONDARY outcome

Timeframe: 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.)

Outcome measures

Outcome measures
Measure	Low-dose Cytarabine Plus Arsenic Trioxide n=33 Participants Cycle 1. 10 mg/m\^2 cytarabine 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 identified from a bone marrow sample taken on day 21 of cycle 1. 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.	Low-dose Cytarabine Alone n=34 Participants 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 treatment was given to patients with persistent disease identified from a bone marrow sample taken on day 21 of cycle 1. 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. 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 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.
Number of Participants Who Died or Were Censored by 24 Months	33 Participants	34 Participants

SECONDARY outcome

Timeframe: From Baseline (randomization) through 24 months following Baseline

Population: Population analyzed are the subjects who who achieved a complete remission (CR), complete remission with incomplete platelet recovery (CRp), or partial remission(PR)during the course of the study

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.

Outcome measures

Outcome measures
Measure	Low-dose Cytarabine Plus Arsenic Trioxide n=21 Participants Cycle 1. 10 mg/m\^2 cytarabine 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 identified from a bone marrow sample taken on day 21 of cycle 1. 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.	Low-dose Cytarabine Alone n=29 Participants 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 treatment was given to patients with persistent disease identified from a bone marrow sample taken on day 21 of cycle 1. 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. 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 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.
Proportion of Participants With Relapse-Free Survival (RFS)Using the Kaplan-Meier Estimate Month 3 (95% Confidence Interval)	0.818 Proportion of participants Interval 0.447 to 0.951	0.800 Proportion of participants Interval 0.204 to 0.969
Proportion of Participants With Relapse-Free Survival (RFS)Using the Kaplan-Meier Estimate Month 6 (95% Confidence Interval)	0.818 Proportion of participants Interval 0.447 to 0.951	0.800 Proportion of participants Interval 0.204 to 0.969

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Low-dose Cytarabine Plus Arsenic Trioxide n=33 Participants Cycle 1. 10 mg/m\^2 cytarabine 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 identified from a bone marrow sample taken on day 21 of cycle 1. 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.	Low-dose Cytarabine Alone n=34 Participants 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 treatment was given to patients with persistent disease identified from a bone marrow sample taken on day 21 of cycle 1. 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. 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 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.
Number of Participants Who Experienced Early Death	0 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Low-dose Cytarabine Plus Arsenic Trioxide n=33 Participants Cycle 1. 10 mg/m\^2 cytarabine 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 identified from a bone marrow sample taken on day 21 of cycle 1. 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.	Low-dose Cytarabine Alone n=34 Participants 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 treatment was given to patients with persistent disease identified from a bone marrow sample taken on day 21 of cycle 1. 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. 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 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.
Number of Participants Who Experienced Induction (Thirty-Day) Mortality	3 Participants	2 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Low-dose Cytarabine Plus Arsenic Trioxide n=33 Participants Cycle 1. 10 mg/m\^2 cytarabine 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 identified from a bone marrow sample taken on day 21 of cycle 1. 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.	Low-dose Cytarabine Alone n=34 Participants 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 treatment was given to patients with persistent disease identified from a bone marrow sample taken on day 21 of cycle 1. 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. 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 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.
Proportion of Participants Surviving at 6 Months and 12 Months Using the Kaplan Meier Estimate Month 6 (95% Confidence Interval)	0.626 Proportion of Participants Interval 0.435 to 0.768	0.649 Proportion of Participants Interval 0.454 to 0.789
Proportion of Participants Surviving at 6 Months and 12 Months Using the Kaplan Meier Estimate Month 12 (95% Confidence Interval)	12.22 Proportion of Participants Interval 4.37 to 16.76	8.51 Proportion of Participants Interval 5.72 to 19.65

Adverse Events

Low-dose Cytarabine Plus Arsenic Trioxide

Serious events: 19 serious events

Other events: 33 other events

Deaths: 0 deaths

Low-dose Cytarabine Alone

Serious events: 21 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Sponsor's Medical Expert, Clinical Research

Cephalon, Inc.

Phone: 1-800-896-5855

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Low-dose Cytarabine Plus Arsenic Trioxide n=33 participants at risk Cycle 1. 10 mg/m\^2 cytarabine 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 identified from a bone marrow sample taken on day 21 of cycle 1. 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.	Low-dose Cytarabine Alone n=33 participants at risk 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 treatment was given to patients with persistent disease identified from a bone marrow sample taken on day 21 of cycle 1. 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. 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 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.
Gastrointestinal disorders Abdominal pain	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Infections and infestations Abscess bacterial	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Immune system disorders Anaphylactic reaction	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
General disorders Asthenia	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Infections and infestations Bacteraemia	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Vascular disorders Capillary leak syndrome	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Cardiac disorders Cardiac failure congestive	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Cardiac disorders Cardio-respiratory arrest	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Cardiac disorders Cardiopulmonary failure	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Infections and infestations Catheter site cellulitis	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Infections and infestations Cellulitis	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
General disorders Chills	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Dehydration	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	6.1% 2/33 • Number of events 2 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Gastrointestinal disorders Diarrhoea	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Blood and lymphatic system disorders Febrile neutropenia	21.2% 7/33 • Number of events 7 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	27.3% 9/33 • Number of events 9 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Fluid overload	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Nervous system disorders Haemorrhage intracranial	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Metabolism and nutrition disorders Hypophagia	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Vascular disorders Hypotension	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
General disorders Infusion related reaction	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Cardiac disorders Left ventricular dysfunction	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	6.1% 2/33 • Number of events 2 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Infections and infestations Neutropenic infection	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Infections and infestations Neutropenic sepsis	6.1% 2/33 • Number of events 2 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Pain in jaw	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Cardiac disorders Pericardial haemorrhage	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Infections and infestations Pneumonia	9.1% 3/33 • Number of events 3 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	9.1% 3/33 • Number of events 3 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Infections and infestations Pneumonia fungal	6.1% 2/33 • Number of events 2 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Gastrointestinal disorders Proctitis	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
General disorders Pyrexia	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Renal and urinary disorders Renal failure	6.1% 2/33 • Number of events 2 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Renal and urinary disorders Renal failure acute	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	6.1% 2/33 • Number of events 2 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory distress	6.1% 2/33 • Number of events 2 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	6.1% 2/33 • Number of events 2 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Infections and infestations Sepsis	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	6.1% 2/33 • Number of events 2 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Infections and infestations Septic shock	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Vascular disorders Shock	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Infections and infestations Staphylococcal bacteraemia	6.1% 2/33 • Number of events 2 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Gastrointestinal disorders Stomatitis	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Nervous system disorders Syncope	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Cardiac disorders Tachycardia	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour lysis syndrome	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Cardiac disorders Ventricular extrasystoles	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.
Gastrointestinal disorders Vomiting	3.0% 1/33 • Number of events 1 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.	0.00% 0/33 • approximately 2 years Adverse events were collected from the date the ICF was signed through 30 days after the last dose of study drug.