Phase I Trial of Vorinostat (MK-0683, SAHA) in Combination With Decitabine in Patients With AML or MDS (MK-0683-055 EXT1)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Merck

ClinicalTrials.gov Identifier:

NCT00479232

First received: May 24, 2007

Last updated: February 5, 2013

Last verified: February 2013

History of Changes

Results First Received: April 28, 2011

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Leukemia, Myelocytic, Acute Myelodysplastic Syndromes Myelodysplastic Syndromes
Interventions:	Drug: vorinostat Drug: decitabine

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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Concurrent, Vorinostat 400mg qd x 7d/4wk + Decitabine	(concurrent) vorinostat 400 mg capsules given once daily (qd) on Days 1 to 7 in a 28 day cycle, along with decitabine intravenous (IV) 20mg/m^2 daily for 5 days in each 28 day cycle, up to 24 months of treatment.
Concurrent, Vorinostat 400mg qd x 7d/2wk + Decitabine	(concurrent) vorinostat 400 mg capsules given qd on Days 1 to 7 and Days 15 to 21 in a 28 day cycle, along with decitabine IV 20mg/m^2 daily for 5 days in each 28 day cycle, up to 24 months of treatment.
Concurrent, Vorinostat 400mg qd x 14d/4wk + Decitabine (MTD)	(concurrent) vorinostat 400 mg capsules given qd on Days 1 to 14 in a 28 day cycle, along with decitabine IV 20mg/m^2 daily for 5 days in each 28 day cycle, up to 24 months of treatment.
Sequential, Vorinostat 400mg qd x 7d/4wk + Decitabine	(sequential) vorinostat 400 mg capsules given qd on Days 6 to 12 in a 28 day cycle, along with decitabine IV 20mg/m^2 daily for 5 days in each 28 day cycle, up to 24 months of treatment.
Sequential, Vorinostat 400mg qd x 10d/4wk + Decitabine	(sequential) vorinostat 400 mg capsules given qd on Days 6 to 15 in a 28 day cycle, along with decitabine IV 20mg/m^2 daily for 5 days in each 28 day cycle, up to 24 months of treatment.
Sequential, Vorinostat 400mg qd x 14d/4wk + Decitabine (MTD)	(sequential) vorinostat 400 mg capsules given qd on Days 6 to 19 in a 28 day cycle, along with decitabine IV 20mg/m^2 daily for 5 days in each 28 day cycle, up to 24 months of treatment.

Participant Flow: Overall Study

	Concurrent, Vorinostat 400mg qd x 7d/4wk + Decitabine	Concurrent, Vorinostat 400mg qd x 7d/2wk + Decitabine	Concurrent, Vorinostat 400mg qd x 14d/4wk + Decitabine (MTD)	Sequential, Vorinostat 400mg qd x 7d/4wk + Decitabine	Sequential, Vorinostat 400mg qd x 10d/4wk + Decitabine	Sequential, Vorinostat 400mg qd x 14d/4wk + Decitabine (MTD)
STARTED	3	3	28	3	4	30
COMPLETED	0	0	0	0	0	0
NOT COMPLETED	3	3	28	3	4	30
Adverse Event	0	0	5	0	0	10
Deviation from Protocol	0	0	1	0	0	0
Lack of Efficacy	0	0	2	0	0	4
Physician Decision	0	0	2	0	0	1
Progressive Disease	3	1	12	3	3	12
Withdrew Consent	0	2	6	0	1	3

Baseline Characteristics

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Reporting Groups

	Description
Vorinostat + Decitabine, Concurrent	(concurrent) Vorinostat 400 mg capsules once daily given 7 days, 14 days with 8 day break after first 7 days or 14 days without break, out of 28 day cycles along with decitabine IV 20 mg/m^2 daily for 5 days in each 28 day cycle. Up to 24 months of treatment.
Vorinostat + Decitabine, Sequential	(sequential) Vorinostat 400 mg capsules once daily given 7, 10 or 14 days in 28 day cycles along with decitabine IV 20 mg/m^2 daily for 5 days in each 28 day cycle. Up to 24 months of treatment.
Total	Total of all reporting groups

Baseline Measures

	Vorinostat + Decitabine, Concurrent	Vorinostat + Decitabine, Sequential	Total
Number of Participants [units: participants]	34	37	71
Age [units: years] Mean ± Standard Deviation	63.9 ± 13.0	66.6 ± 13.8	65.3 ± 13.4
Gender [units: participants]
Female	11	18	29
Male	23	19	42

Outcome Measures

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1. Primary:

Number of Participants Experiencing Dose Limiting Toxicity (DLT) Events [ Time Frame: Day 1 to 28 of Cycle 1 ]

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2. Other Pre-specified:

Objective Response Rate in Participants Treated With Vorinostat + Decitabine With Refractory or Relapse Acute Myelogenous Leukemia (AML) [ Time Frame: Approximately 6 months ]

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3. Other Pre-specified:

Objective Response Rate in Participants Treated With Vorinostat + Decitabine With Intermediate-high Risk Myelodysplastic Syndrome (MDS) or Untreated Acute Myelogenous Leukemia (AML) [ Time Frame: Approximately 6 months ]

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Measure Type	Other Pre-specified
Measure Title	Objective Response Rate in Participants Treated With Vorinostat + Decitabine With Intermediate-high Risk Myelodysplastic Syndrome (MDS) or Untreated Acute Myelogenous Leukemia (AML)
Measure Description	Objective Response Rate was measured in participants with intermediate-high risk MDS or untreated AML who were treated with vorinostat and decitabine either on a concurrent or sequential regimen. The Objective response was defined as any confirmed complete remission or any confirmed partial remission for AML participants and complete remission, confirmed partial remission or confirmed hematologic improvement for MDS participants.
Time Frame	Approximately 6 months
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
Untreated AML or Intermediate, Concurrent	Participants with Untreated AML or Intermediate-High Risk MDS who were treated with vorinostat and Decitabine concurrently.
Untreated AML or Intermediate, Sequential	Participants with Untreated AML or Intermediate-High Risk MDS who were treated with vorinostat and Decitabine sequentially.

Measured Values

	Untreated AML or Intermediate, Concurrent	Untreated AML or Intermediate, Sequential
Number of Participants Analyzed [units: participants]	20	22
Objective Response Rate in Participants Treated With Vorinostat + Decitabine With Intermediate-high Risk Myelodysplastic Syndrome (MDS) or Untreated Acute Myelogenous Leukemia (AML) [units: percentage of participants]	35.0	13.6

No statistical analysis provided for Objective Response Rate in Participants Treated With Vorinostat + Decitabine With Intermediate-high Risk Myelodysplastic Syndrome (MDS) or Untreated Acute Myelogenous Leukemia (AML)

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. Restriction Description: The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.

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
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Results Point of Contact:

Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com

No publications provided

Responsible Party:	Merck
ClinicalTrials.gov Identifier:	NCT00479232 History of Changes
Other Study ID Numbers:	MK-0683-055, 2007_500
Study First Received:	May 24, 2007
Results First Received:	April 28, 2011
Last Updated:	February 5, 2013
Health Authority:	United States: Food and Drug Administration

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