Acute Myeloid LeukemiaPhase 3NCT00513305

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

A Phase 3 study testing Arsenic trioxide and Low-dose cytarabine alone in people with Acute Myeloid Leukemia, run by Cephalon at 12 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 60 years and older
Conditions the study is for: Acute Myeloid Leukemia
What is being tested?: Arsenic trioxide and Low-dose cytarabine alone
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 67 participants
Where: 12 sitesin 2 countries
Study dates: Oct 2007to Dec 2009
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 60 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

12 sites in 2 countries.

Country

City, postcode or hospital

12 sites in 2 countries

United States11 sites

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

Other trials in United States

Canada1 site

Princess Margaret Hospital
Toronto, Ontario, M5G2M9

Other trials in Canada

About this study

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

Conditions: Acute Myeloid Leukemia
Being tested: Arsenic trioxide, Low-dose cytarabine alone
Keywords: acute myeloid leukemia, cytarabine, arsenic trioxide.
Medical subject headings: Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Arsenic trioxideDrug
Arsenic trioxide will be administered intravenously (iv) at a dose of 0.25 mg/kg.
Low-dose cytarabine aloneDrug
Cytarabine will be administered at a dose of 10 mg/m^2 subcutaneously (sc) twice a day (bid).

Study groups in NCT00513305
Study group	Role	What they receive
Low-dose cytarabine plus arsenic trioxide	Active comparator	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. Receives: Drug: Arsenic trioxide; Drug: Low-dose cytarabine alone
Low-dose cytarabine alone	Active comparator	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. Receives: Drug: Low-dose cytarabine alone

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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 outcomes (5)

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.)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline through 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 2007Dec 2009

First posted8 Aug 2007 (estimated)
Study startOct 2007
Primary completionJul 2009
Study completionDec 2009

Why it stopped: Study has been stopped by sponsor decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 67 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00513305
Sponsor's protocol ID: C18477/3059/AM/US-CA
Status last verified: Jul 2012
First submitted: 6 Aug 2007
Last updated: 1 Aug 2012
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Acute Myeloid Leukemia trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT00513305
Acronym / sponsor ID: C18477/3059/AM/US-CA
Conditions: Acute Myeloid Leukemia
Keywords: acute myeloid leukemia, cytarabine, arsenic trioxide.
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study has been stopped by sponsor decision
Enrolment: 67 participants (actual)
Lead sponsor: CephalonIndustry (pharma, biotech, devices)
Study start: Oct 2007
Primary completion: Jul 2009 (actual)
Study completion: Dec 2009 (actual)
First posted: 8 Aug 2007 (estimated)
Results: Posted 29 Mar 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Low-dose cytarabine plus arsenic trioxide	Active comparator	Drug: Arsenic trioxide, Drug: Low-dose cytarabine aloneCycle 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.
Low-dose cytarabine alone	Active comparator	Drug: Low-dose cytarabine aloneCytarabine 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.

Who may qualify

Ages: 60 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (7 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Arsenic trioxideArsenic trioxide will be administered intravenously (iv) at a dose of 0.25 mg/kg.	Drug	Low-dose cytarabine plus arsenic trioxide
Low-dose cytarabine aloneCytarabine will be administered at a dose of 10 mg/m^2 subcutaneously (sc) twice a day (bid).	Drug	Low-dose cytarabine alone, Low-dose cytarabine plus arsenic trioxide

Primary outcome

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.

5 secondary outcomes

Number of Participants Who Died or Were Censored by 24 Months
Time frame: From Baseline through 24 months following Baseline
Proportion of Participants With Relapse-Free Survival (RFS)Using the Kaplan-Meier Estimate
Time frame: From Baseline (randomization) through 24 months following Baseline
Number of Participants Who Experienced Early Death
Time frame: 14 days from start of study drug treatment
Number of Participants Who Experienced Induction (Thirty-Day) Mortality
Time frame: 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
Time frame: Baseline through 12 months

Results and safety

Results posted to the registry on 29 Mar 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Low-dose Cytarabine Plus Arsenic Trioxide	33	5
Low-dose Cytarabine Alone	34	7

Primary outcome: 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. Number. Unit: Percentage of participants in CR

Measure	Low-dose Cytarabine Plus Arsenic Trioxide n = 33	Low-dose Cytarabine Alone n = 34
Value	15.2 (0.051 to 0.319)	8.8 (0.019 to 0.0237)

Low-dose Cytarabine Plus Arsenic Trioxide vs Low-dose Cytarabine Alone: p = 0.425, Chi-squared

Population analysed: Intention to treat (ITT) Analysis Set

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: approximately 2 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Low-dose Cytarabine Plus Arsenic Trioxide	19 of 33 (57.6%)	33 of 33 (100%)	Not reported
Low-dose Cytarabine Alone	21 of 33 (63.6%)	33 of 33 (100%)	Not reported

Limitations and caveats (from the sponsor): In September 2009, the sponsor decided to stop the study due to difficulty in enrollment. The study was stopped prior to the first planned interim analysis. Most of the analysis planned in the protocol was not performed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2012.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

12 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Arsenic trioxide and Low-dose cytarabine alone in people with Acute Myeloid Leukemia, run by Cephalon at 12 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Mar 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00513305.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2012.