A Multicenter, Open-Label, Phase I Study of MK-0683 in Combination With Bortezomib in Patients With Relapsed and/or Refractory Multiple Myeloma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 9
- Primary Endpoint
- Number of Participants With Dose-Limiting Toxicity (DLT) During Cycle 1
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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).
Intervention: Vorinostat (Drug)
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).
Intervention: Bortezomib (Drug)
Outcomes
Primary Outcomes
Number of Participants With Dose-Limiting Toxicity (DLT) During Cycle 1
Time Frame: Up to 21 days
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).
Secondary Outcomes
No secondary outcomes reported