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

This study has been terminated.

(Study has been stopped by sponsor decision)

Sponsor:

Information provided by (Responsible Party):

Teva Pharmaceutical Industries ( Cephalon )

ClinicalTrials.gov Identifier:

NCT00513305

First received: August 6, 2007

Last updated: July 24, 2012

Last verified: July 2012

History of Changes

Results First Received: July 29, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Acute Myeloid Leukemia
Interventions:	Drug: Arsenic trioxide Drug: Low-dose cytarabine alone

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

Description

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.

Participant Flow: Overall Study

	Low-dose Cytarabine Plus Arsenic Trioxide	Low-dose Cytarabine Alone
STARTED	33	34 ^[1]
COMPLETED	5	7
NOT COMPLETED	28	27
Adverse Event	6	2
Death (through Consolidation Treatment)	2	2
Lack of Efficacy	8	13
Withdrawal by Subject	1	2
Disease progression	8	5
Eligible for stem cell transplant	1	0
Hematologic counts did not recover	1	0
Physician Decision	1	0
Persistent hypocellularity	0	1
Sponsor Decision	0	2

[1]	One subject withdrew prior to receiving study medication

Baseline Characteristics

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Reporting Groups

	Description
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.
Total	Total of all reporting groups

Baseline Measures

	Low-dose Cytarabine Plus Arsenic Trioxide	Low-dose Cytarabine Alone	Total
Number of Participants [units: participants]	33	34	67
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	9	7	16
>=65 years	24	27	51
Age [units: years] Mean ± Standard Deviation	70.9 ± 7.1	71.5 ± 6.8	71.2 ± 6.9
Gender [units: participants]
Female	16	17	33
Male	17	17	34
Region of Enrollment [units: participants]
United States	32	32	64
Canada	1	2	3

Outcome Measures

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1. Primary:

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 ]

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2. Secondary:

Number of Participants Who Died or Were Censored by 24 Months [ Time Frame: From Baseline through 24 months following Baseline ]

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3. Secondary:

Proportion of Participants With Relapse-Free Survival (RFS)Using the Kaplan-Meier Estimate [ Time Frame: From Baseline (randomization) through 24 months following Baseline ]

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4. Secondary:

Number of Participants Who Experienced Early Death [ Time Frame: 14 days from start of study drug treatment ]

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5. Secondary:

Number of Participants Who Experienced Induction (Thirty-Day) Mortality [ Time Frame: Up to 30 days following start of study drug treatment ]

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6. Secondary:

Proportion of Participants Surviving at 6 Months and 12 Months Using the Kaplan Meier Estimate [ Time Frame: Baseline through 12 months ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.

Results Point of Contact:

Name/Title: Sponsor's Medical Expert, Clinical Research
Organization: Cephalon, Inc.
phone: 1-800-896-5855

No publications provided

Responsible Party:	Teva Pharmaceutical Industries ( 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:	July 24, 2012
Health Authority:	United States: Food and Drug Administration

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