Phase 1 Study of Vorinostat and Bortezomib in Multiple Myeloma (MK-0683-015 EXT 1 (AM1))

Experimental: vorinostat 200 mg + bortezomib 0.7 mg/m^2

Vorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.

Droga: vorinostat

Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).

Otros nombres:

• Zolinza®
• MK0683
• Ácido hidroxámico de suberoilanilida (SAHA)

Droga: bortezomib

Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.

Otros nombres:

• Velcade

Experimental: vorinostat 200 mg + bortezomib 0.9 mg/m^2

Vorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.

Droga: vorinostat

Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).

Otros nombres:

• Zolinza®
• MK0683
• Ácido hidroxámico de suberoilanilida (SAHA)

Droga: bortezomib

Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.

Otros nombres:

• Velcade

Experimental: vorinostat 300 mg + bortezomib 1.3 mg/m^2

Vorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle.

Droga: vorinostat

Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).

Otros nombres:

• Zolinza®
• MK0683
• Ácido hidroxámico de suberoilanilida (SAHA)

Droga: bortezomib

Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.

Otros nombres:

• Velcade

Experimental: vorinostat 400 mg + bortezomib 0.9 mg/m^2

Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.

Droga: vorinostat

Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).

Otros nombres:

• Zolinza®
• MK0683
• Ácido hidroxámico de suberoilanilida (SAHA)

Droga: bortezomib

Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.

Otros nombres:

• Velcade

Experimental: vorinostat 400 mg + bortezomib 1.1 mg/m^2

Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.

Droga: vorinostat

Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).

Otros nombres:

• Zolinza®
• MK0683
• Ácido hidroxámico de suberoilanilida (SAHA)

Droga: bortezomib

Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.

Otros nombres:

• Velcade

Experimental: vorinostat 400 mg + bortezomib 1.3 mg/m^2

Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.

Droga: vorinostat

Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).

Otros nombres:

• Zolinza®
• MK0683
• Ácido hidroxámico de suberoilanilida (SAHA)

Droga: bortezomib

Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.

Otros nombres:

• Velcade

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.

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.

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.

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.

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.