Phase 1 Study of Vorinostat and Bortezomib in Multiple My... | NCT00111813

ID	Type	Description	Link
2005_018

Phase 1 Study of Vorinostat and Bortezomib in Multiple My... | NCT00111813 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
vorinostat 200 mg + bortezomib 0.7 mg/m^2	Experimental	Vorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.	Drug: vorinostat Drug: bortezomib
vorinostat 200 mg + bortezomib 0.9 mg/m^2	Experimental	Vorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.	Drug: vorinostat Drug: bortezomib
vorinostat 300 mg + bortezomib 1.3 mg/m^2	Experimental	Vorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle.	Drug: vorinostat Drug: bortezomib
vorinostat 400 mg + bortezomib 0.9 mg/m^2	Experimental	Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.	Drug: vorinostat Drug: bortezomib
vorinostat 400 mg + bortezomib 1.1 mg/m^2	Experimental	Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
vorinostat	Drug	Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).	vorinostat 200 mg + bortezomib 0.7 mg/m^2

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Duration of Treatment With Vorinostat	Event causing discontinuation from the study was defined as (1) progressive disease OR (2) intolerable toxicity. Progressive disease was defined as: >25% increase in the level of serum monoclonal paraprotein. 25% increase in 24-hour urinary light chain excretion. >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy. Development of new bone lesions or soft tissue plasmacytomas. Development of hypercalcemia. Intolerable toxicity was based on the clinical judgment of the investigator.	Day 1 to an event causing discontinuation from the study, assessed up to 29 months

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug	An adverse experience (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.

Name	Affiliation	Role
Medical Monitor	Merck Sharp & Dohme LLC	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23040438	Derived	Weber DM, Graef T, Hussein M, Sobecks RM, Schiller GJ, Lupinacci L, Hardwick JS, Jagannath S. Phase I trial of vorinostat combined with bortezomib for the treatment of relapsing and/or refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):319-24. doi: 10.1016/j.clml.2012.07.007.

Arm/Group Information

ID	Title	Description
FG000	Vorinostat 200 mg + Bortezomib 0.7 mg/m^2	Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).
FG001	Vorinostat 200 mg + Bortezomib 0.9 mg/m^2	Vorinostat capsules given b.i.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).
FG002	Vorinostat 300 mg + Bortezomib 1.3 mg/m^2	Vorinostat capsules given once daily (q.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
FG003	Vorinostat 400 mg + Bortezomib 0.9 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
FG004	Vorinostat 400 mg + Bortezomib 1.1 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
FG005	Vorinostat 400 mg + Bortezomib 1.3 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0003 subjects FG0013 subjects FG00210 subjects FG0036 subjects FG0046 subjects FG0056 subjects
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0031 subjects FG004
NOT COMPLETED		FG0003 subjects FG0013 subjects FG00210 subjects FG0035 subjects FG004

Type	Comment	Reasons
Adverse Event		FG0001 subjects FG0012 subjects FG0024 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	All Participants	Vorinostat capsules given 200 mg b.i.d., 300 mg q.d., or 400 mg q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib 0.7 mg/m^2, 0.9 mg/m^2, 1.1 mg/m^2, or 1.3 mg/m^2 twice weekly on Days 1, 4, 8, and 11 or on Days 4, 8, 11, and 15 of each cycle, depending on dose level.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Duration of Treatment With Vorinostat

Event causing discontinuation from the study was defined as (1) progressive disease OR (2) intolerable toxicity.

Progressive disease was defined as:

>25% increase in the level of serum monoclonal paraprotein.
25% increase in 24-hour urinary light chain excretion.
>25% increase in plasma cells in a bone marrow aspirate or on trephine

biopsy.

Development of new bone lesions or soft tissue plasmacytomas.
Development of hypercalcemia.

Intolerable toxicity was based on the clinical judgment of the investigator.

Posted

Mean

Full Range

Days

Day 1 to an event causing discontinuation from the study, assessed up to 29 months

ID	Title	Description
OG000	All Participants	Vorinostat capsules given 200 mg b.i.d., 300 mg q.d., or 400 mg q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib 0.7 mg/m^2, 0.9 mg/m^2, 1.1 mg/m^2, or 1.3 mg/m^2 twice weekly on Days 1, 4, 8, and 11 or on Days 4, 8, 11, and 15 of each cycle, depending on dose level.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Vorinostat 200 mg + Bortezomib 0.7 mg/m^2	Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Neutropenia	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 12.1	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Senior Vice President, Global Clinical Development	Merck Sharp & Dohme Corp	1-800-672-6372		ClinicalTrialsDisclosure@merck.com

Condition Browse Module

ID	Term
D009101	Multiple Myeloma

ID	Term
D054219	Neoplasms, Plasma Cell
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D020141	Hemostatic Disorders

Intervention Browse Module

ID	Term
D000077337	Vorinostat
D000069286	Bortezomib

ID	Term
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814	Aniline Compounds

Secondary

Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug

An adverse experience (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.

Posted

Number

Participants

Day 1 to disease progression, toxicity, or death, assessed up to 29 months

ID	Title	Description
OG000	Vorinostat 200 mg + Bortezomib 0.7 mg/m^2	Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).
OG001	Vorinostat 200 mg + Bortezomib 0.9 mg/m^2	Vorinostat capsules given b.i.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).
OG002	Vorinostat 300 mg + Bortezomib 1.3 mg/m^2	Vorinostat capsules given once daily (q.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG003	Vorinostat 400 mg + Bortezomib 0.9 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG004	Vorinostat 400 mg + Bortezomib 1.1 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG005	Vorinostat 400 mg + Bortezomib 1.3 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Units	Counts
Participants	OG0003 OG0013 OG00210 OG003

Title

Denominators

Categories

No dose modification

Title	Measurements
	OG0003 OG0013 OG0028 OG003

Secondary

Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.

Posted

Mean

Standard Deviation

Days

Day 1 to disease progression, toxicity, or death, assessed up to 29 months

ID	Title	Description
OG000	Vorinostat 200 mg + Bortezomib 0.7 mg/m^2	Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).
OG001	Vorinostat 200 mg + Bortezomib 0.9 mg/m^2	Vorinostat capsules given b.i.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).
OG002	Vorinostat 300 mg + Bortezomib 1.3 mg/m^2	Vorinostat capsules given once daily (q.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG003	Vorinostat 400 mg + Bortezomib 0.9 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG004	Vorinostat 400 mg + Bortezomib 1.1 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG005	Vorinostat 400 mg + Bortezomib 1.3 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Units	Counts
Participants	OG0003 OG0013 OG00210 OG003

Title

Denominators

Categories

Title	Measurements
	OG000NA± NANo participants had a dose modification at this dose. OG001NA± NANo participants had a dose modification at this dose. OG00258± 39

Secondary

Clinical AE Summary

An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition.

A serious AE (SAE) was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.

Posted

Number

Participants

Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months)

ID	Title	Description
OG000	Vorinostat 200 mg + Bortezomib 0.7 mg/m^2	Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).
OG001	Vorinostat 200 mg + Bortezomib 0.9 mg/m^2	Vorinostat capsules given b.i.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).
OG002	Vorinostat 300 mg + Bortezomib 1.3 mg/m^2	Vorinostat capsules given once daily (q.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG003	Vorinostat 400 mg + Bortezomib 0.9 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG004	Vorinostat 400 mg + Bortezomib 1.1 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG005	Vorinostat 400 mg + Bortezomib 1.3 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Units	Counts
Participants	OG0003 OG0013 OG00210 OG003

Title

Denominators

Categories

With one or more AEs

Title	Measurements
	OG0003 OG0013 OG00210 OG003

Secondary

Laboratory AE Summary

An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition.

A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.

A lab (S)AE was any lab value considered clinically significant in the investigator's judgment.

Posted

Number

Participants

Day 1 up to disease progression, toxicity, or death, assessed up to 29 months

ID	Title	Description
OG000	Vorinostat 200 mg + Bortezomib 0.7 mg/m^2	Vorinostat capsules given twice daily (b.i.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).
OG001	Vorinostat 200 mg + Bortezomib 0.9 mg/m^2	Vorinostat capsules given b.i.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 4, 8, 11, and 15 of each cycle).
OG002	Vorinostat 300 mg + Bortezomib 1.3 mg/m^2	Vorinostat capsules given once daily (q.d.). Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG003	Vorinostat 400 mg + Bortezomib 0.9 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG004	Vorinostat 400 mg + Bortezomib 1.1 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).
OG005	Vorinostat 400 mg + Bortezomib 1.3 mg/m^2	Vorinostat capsules given q.d. Treatment in 21 day cycles (participants received vorinostat for 14 days followed by a 7 day break). Bortezomib injection. Treatment in 21 day cycles (participants received bortezomib on Days 1, 4, 8, and 11 of each cycle).

Units	Counts
Participants	OG0003 OG0013 OG00210 OG003

Title

Denominators

Categories

With one or more laboratory AEs

Title	Measurements
	OG0001 OG0011 OG0023 OG003