Phase I Study of MK-0683 in Combination With Bortezomib in Participants With Multiple Myeloma (MK-0683-098)

A Multicenter, Open-Label, Phase I Study of MK-0683 in Combination With Bortezomib in Patients With Relapsed and/or Refractory Multiple Myeloma

The primary purpose of this clinical study is to determine the recommended clinical doses of vorinostat (MK-0683) and bortezomib administered in combination to participants with relapsed and/or refractory multiple myeloma (MM). It was hypothesized that administration of vorinostat in combination with bortezomib is sufficiently safe and tolerated well enough to permit further study in participants with relapsed and/or refractory MM. Study results are based on data collected up to the data cut-off date of 20-March-2011.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Vorinostat; Drug: Bortezomib

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• is ≥20 years of age.
• has an established diagnosis of MM based on the myeloma diagnostic criteria
• has received at least 1 but not more than 3 prior anti-myeloma regimens and has progressive disease after the most recent treatment regimen
• has adequate organ function

Exclusion Criteria:

• has had a prior allogeneic bone marrow transplant or plans to undergo any type of bone marrow transplantation during the study
• has known hypersensitivity to any components of vorinostat or bortezomib
• has active hepatitis B or C, plasma cell leukemia, or is human immunodeficiency virus (HIV) positive
• has had prior treatment with vorinostat or histone deacetylase (HDAC) inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Vorinostat + Bortezomib; Participants undergo up to 3 successive 21-day treatment cycles. During Cycle 1, participants receive vorinostat (400 mg once daily [QD] on Days 1 through 14) + bortezomib (1.3 mg/m^2 intravenous [IV] on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 2 participants receive vorinostat (400 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11). If that dose is not well tolerated, during Cycle 3 participants receive vorinostat (300 mg QD on Days 1 through 14) + bortezomib (1.0 mg/m^2 IV on Days 1, 4, 8, and 11).

Drug: Vorinostat; Vorinostat (MK-0683) three or four 100 mg capsules taken by mouth with food.; Other Names: MK-0683; ZOLINZA™; Drug: Bortezomib; Bortezomib (1.0 or 1.3 mg/m^2) intravenous infusion.; Other Names: VELCADE®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-Limiting Toxicity (DLT) During Cycle 1	The number of participants with ≥1 DLT during Cycle 1 is reported. A DLT is defined as an event considered by the investigator to be related to study treatment, and either: 1) a Grade 3 or 4 non-hematologic event (except for manageable toxicity by supportive care or non-prohibited therapies, or a transient increase in alanine aminotransferase [ALT]/aspartate aminotransferase [AST]); or 2) a Grade 4 hematologic toxicity except neutropenia or hemoglobin decreased (neutropenia was a DLT if it was Grade 3-4 with fever ≥38.5°C; Grade 3-4 with an infection requiring antibiotic/antifungal therapy; or Grade 4 and lasting ≥5 days).	Up to 21 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With an Adverse Event (AE)	The number of participants with ≥1 AE is reported. An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study product(s), whether or not considered related to the use of the product(s).	Up to 346 days (up to 30 days after the final dose of study treatment)
Area Under the Plasma Concentration-Time Curve From 0 to 24 Hours Postdose (AUC0-24hr) of Vorinostat Administered With Bortezomib on Days 1 and 11	The AUC0-24hr of vorinostat in plasma on Days 1 and 11 is reported in participants who also received bortezomib.	Predose and 0.8, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Days 1 and 11

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Ogawa Y, Ogura M, Tobinai K, Ando K, Suzuki T, Watanabe T, Ohmachi K, Uchida T, Hanson ME, Tanaka Y, Koh Y, Shimamoto T, Hotta T. A phase I study of vorinostat combined with bortezomib in Japanese patients with relapsed or refractory multiple myeloma. Int J Hematol. 2016 Jan;103(1):25-33. doi: 10.1007/s12185-015-1897-7. Epub 2015 Nov 30.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2009
• Primary Completion (Actual): June 11, 2010
• Study Completion (Actual): April 19, 2012

Study Registration Dates

• First Submitted: March 4, 2009
• First Submitted That Met QC Criteria: March 6, 2009
• First Posted (Estimate): March 9, 2009

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 7, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Bortezomib; Vorinostat
• Other Study ID Numbers: 0683-098; MK-0683-098 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf