Phase 1 Study of Vorinostat and Bortezomib in Multiple Myeloma (MK-0683-015 EXT 1 (AM1))
- Registration Number
- NCT00111813
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 34
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description vorinostat 400 mg + bortezomib 0.9 mg/m^2 vorinostat Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle. vorinostat 200 mg + bortezomib 0.9 mg/m^2 bortezomib Vorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle. vorinostat 200 mg + bortezomib 0.7 mg/m^2 bortezomib Vorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle. vorinostat 200 mg + bortezomib 0.7 mg/m^2 vorinostat Vorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle. vorinostat 200 mg + bortezomib 0.9 mg/m^2 vorinostat Vorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle. vorinostat 300 mg + bortezomib 1.3 mg/m^2 vorinostat Vorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle. vorinostat 400 mg + bortezomib 1.1 mg/m^2 bortezomib Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle. vorinostat 300 mg + bortezomib 1.3 mg/m^2 bortezomib Vorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle. vorinostat 400 mg + bortezomib 0.9 mg/m^2 bortezomib Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle. vorinostat 400 mg + bortezomib 1.1 mg/m^2 vorinostat Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle. vorinostat 400 mg + bortezomib 1.3 mg/m^2 vorinostat Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle. vorinostat 400 mg + bortezomib 1.3 mg/m^2 bortezomib Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
- Primary Outcome Measures
Name Time Method Mean Duration of Treatment With Vorinostat Day 1 to an event causing discontinuation from the study, assessed up to 29 months 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug Day 1 to disease progression, toxicity, or death, assessed up to 29 months 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 Day 1 to disease progression, toxicity, or death, assessed up to 29 months 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 Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months) 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 Day 1 up to disease progression, toxicity, or death, assessed up to 29 months 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.