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

Multiple Myeloma Clinical Trial

Official title:

Phase I Clinical Trial of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Advanced Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00111813
• Other study ID #: 0683-015
• Secondary ID: 2005_018
• Status: Completed
• Phase: Phase 1
• First received: May 25, 2005
• Last updated: May 5, 2015
• Start date: September 2005
• Est. completion date: May 2011

Study information

• Verified date: May 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purposes of this study are:

• To determine the maximum tolerated dose (MTD) for the combination of oral vorinostat and bortezomib in participants with advanced multiple myeloma

• To assess the safety and tolerability of this regimen and to document the participant's clinical status (by anti-tumor activity) for this combination, as determined per standard of care.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: May 2011
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults with refractory or relapsed multiple myeloma

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (a measurement to determine participant's ability to perform daily activities)

• Adequate bone marrow reserve

• Adequate hepatic and renal function

• Ability to swallow capsules

• 3 weeks or more since prior chemotherapy and have recovered from prior toxicities

Exclusion Criteria:

• Participants who plan to have a bone marrow transplant within 4 weeks of start of treatment

• Participants with prior treatment with other investigational agents with a similar anti-tumor mechanism

• Participants with other active/uncontrolled clinically significant illness

• Pregnant or nursing female participants

• Participants who received bortezomib within 3 months of start of this trial

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• vorinostat
Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).
• bortezomib
Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Day 1 to an event causing discontinuation from the study, assessed up to 29 months	Yes
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.	Day 1 to disease progression, toxicity, or death, assessed up to 29 months	Yes
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.	Day 1 to disease progression, toxicity, or death, assessed up to 29 months	Yes
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.	Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months)	Yes
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.	Day 1 up to disease progression, toxicity, or death, assessed up to 29 months	Yes