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

Browse trials for

• Multiple Myeloma 3,632
• Neoplasms, Plasma Cell 2,306

Multiple Myeloma

3,632 studies on the registry are indexed under Multiple Myeloma; 745 are open to participants now.

This study's enrollment of 34 is below the median of 41 across 2,907 interventional studies indexed under Multiple Myeloma.

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Study arms

• Experimental
  vorinostat 200 mg + bortezomib 0.7 mg/m^2

  Vorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.

  Drug: vorinostat · Drug: bortezomib

• Experimental
  vorinostat 200 mg + bortezomib 0.9 mg/m^2

  Vorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.

  Drug: vorinostat · Drug: bortezomib

• Experimental
  vorinostat 300 mg + bortezomib 1.3 mg/m^2

  Vorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle.

  Drug: vorinostat · Drug: bortezomib

• Experimental
  vorinostat 400 mg + bortezomib 0.9 mg/m^2

  Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.

  Drug: vorinostat · Drug: bortezomib

• Experimental
  vorinostat 400 mg + bortezomib 1.1 mg/m^2

  Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.

  Drug: vorinostat · Drug: bortezomib

• Experimental
  vorinostat 400 mg + bortezomib 1.3 mg/m^2

  Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.

  Drug: vorinostat · Drug: bortezomib

Interventions

• Drugvorinostat

  Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).

  Also known as: MK0683, Zolinza®, Suberoylanilide Hydroxamic Acid (SAHA)

• Drugbortezomib

  Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.

  Also known as: Velcade

Primary outcomes

1. 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.

   Time frame: Day 1 to an event causing discontinuation from the study, assessed up to 29 months

Secondary outcomes

1. 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.

   Time frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months

2. 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.

   Time frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months

3. 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.

   Time frame: Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months)

4. 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.

   Time frame: Day 1 up to disease progression, toxicity, or death, assessed up to 29 months

Baseline characteristics

Publications

• Weber DM, Graef T, Hussein M, Sobecks RM, Schiller GJ, Lupinacci L, Hardwick JS, Jagannath S. Phase I trial of vorinostat combined with bortezomib for the treatment of relapsing and/or refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):319-24. doi: 10.1016/j.clml.2012.07.007. PubMed 23040438 ↗