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

NCT00858234 | Completed Phase 1 Results

• 2 other identifiers: 0683-098MK-0683-098
• Study Type: interventional
• Target: 9
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of Participants With an Adverse Event (AE)

  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

  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

Study Arms (1)

Vorinostat + Bortezomib

EXPERIMENTAL

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; Drug: Bortezomib

Interventions

Vorinostat DRUG

Vorinostat (MK-0683) three or four 100 mg capsules taken by mouth with food.

Also known as: MK-0683, ZOLINZA™

Vorinostat + Bortezomib

Bortezomib DRUG

Bortezomib (1.0 or 1.3 mg/m\^2) intravenous infusion.

Also known as: VELCADE®

Vorinostat + Bortezomib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 26619834 RESULT

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Vorinostat; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Monitor

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2009
• First Posted: March 9, 2009
• Study Start: February 13, 2009
• Primary Completion: June 11, 2010
• Study Completion: April 19, 2012
• Last Updated: April 9, 2021
• Results First Posted: April 9, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share