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

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Primary Purpose

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Arsenic trioxide

Low-dose cytarabine alone

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring acute myeloid leukemia, cytarabine, arsenic trioxide.

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Low-dose cytarabine plus arsenic trioxide

Low-dose cytarabine alone

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.)

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.

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.

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.

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.

Full Information

NCT ID

NCT00513305

First Posted

August 6, 2007

Last Updated

July 24, 2012

Sponsor

Cephalon

1. Study Identification

Unique Protocol Identification Number

NCT00513305

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2012

Overall Recruitment Status

Terminated

Why Stopped

Study has been stopped by sponsor decision

Study Start Date

October 2007 (undefined)

Primary Completion Date

July 2009 (Actual)

Study Completion Date

December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cephalon

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

Keywords

acute myeloid leukemia, cytarabine, arsenic trioxide.

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

67 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Low-dose cytarabine plus arsenic trioxide

Arm Type

Active Comparator

Arm Description

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.

Arm Title

Low-dose cytarabine alone

Arm Type

Active Comparator

Arm Description

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 Type

Drug

Intervention Name(s)

Arsenic trioxide

Intervention Description

Arsenic trioxide will be administered intravenously (iv) at a dose of 0.25 mg/kg.

Intervention Type

Drug

Intervention Name(s)

Low-dose cytarabine alone

Intervention Description

Cytarabine will be administered at a dose of 10 mg/m^2 subcutaneously (sc) twice a day (bid).

Primary Outcome Measure Information:

Title

Percentage of Participants in Complete Remission (CR)

Description

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.

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

Secondary Outcome Measure Information:

Title

Number of Participants Who Died or Were Censored by 24 Months

Description

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.)

Time Frame

From Baseline through 24 months following Baseline

Title

Proportion of Participants With Relapse-Free Survival (RFS)Using the Kaplan-Meier Estimate

Description

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.

Time Frame

From Baseline (randomization) through 24 months following Baseline

Title

Number of Participants Who Experienced Early Death

Description

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.

Time Frame

14 days from start of study drug treatment

Title

Number of Participants Who Experienced Induction (Thirty-Day) Mortality

Description

The number of subjects who died from any cause within the first 30 days after the start of study drug treatment is presented here.

Time Frame

Up to 30 days following start of study drug treatment

Title

Proportion of Participants Surviving at 6 Months and 12 Months Using the Kaplan Meier Estimate

Description

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.

Time Frame

Baseline through 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

No

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.

Facility Information:

Facility Name

USC / Norris Cancer Hospital

City

Los Angeles

State/Province

California

ZIP/Postal Code

90033

Country

United States

Facility Name

UCLA Medical Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

University of Illinois

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

Indiana Oncology Hematology Consultants

City

Indianapolis

State/Province

Indiana

ZIP/Postal Code

46202

Country

United States

Facility Name

Roswell Park Cancer Institute

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263

Country

United States

Facility Name

St. Vincent's Comprehensive Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10011

Country

United States

Facility Name

Weill Medical College of Cornell University

City

New York

State/Province

New York

ZIP/Postal Code

10021

Country

United States

Facility Name

Brody School of Medicine

City

Greenville

State/Province

North Carolina

ZIP/Postal Code

27834

Country

United States

Facility Name

University of Oklahoma

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73104

Country

United States

Facility Name

Medical University of South Carolina

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

UT Health Science Center

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

Princess Margaret Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G2M9

Country

Canada

Acute Myeloid Leukemia

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial