Aurora A Kinase Inhibitor MLN8237 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma
RATIONALE: Aurora A kinase inhibitor MLN8237 and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I/II trial is studying the side effects and best dose of giving aurora A kinase inhibitor MLN8237 together with bortezomib and to see how well they work in treating patients with relapsed or refractory multiple myeloma.
|Refractory Multiple Myeloma||Drug: Aurora A kinase inhibitor MLN8237 Drug: bortezomib||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Combination of Aurora Kinase Inhibitor MLN8237 and Bortezomib in Relapsed or Refractory Multiple Myeloma|
- Dose-limiting Toxicity (DLT) (Phase I) [ Time Frame: 28 days ]
Patients were evaluated over the first cycle of treatment for Dose Limiting Toxicities. For this trail DLTs are as follows:
An AE attributed (definitely, probably, or possibly) to study treatment during cycle 1 and the following criteria:
Grade 4 Neutropenia Grade 4 Thrombocytopenia, or grade 3 with bleeding Febrile neutropenia Creatinine serum great than 2 times baseline or upper limit of normal Grade 3 or higher Fatigue Grade 3 or higher nausea, vomiting, or diarrhea Any grade 3 or higher Non-hematologic toxicity per NCI CTCAE V4.0 Inability to initiate the scheduled cycle 2, day 1 due to toxicity
The maximum tolerated dose level (MTD) will be defined as the highest safely tolerated dose.
- Overall Response Rate to the Combination of MLN8237 and Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma. [ Time Frame: Every 28 day cycle(up to 10 cycles) ]sCR: Normal serum FLC ratio, and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence, negative immunofixation of the serum and urine, <5% plasma cells in bone marrow, disappearance of any soft tissue plasmacytomas, and normalization of FLC ratio. VGPR:PR and serum and urine M-component detectable by immunofixation but not on electrophoresis, or if serum measurable,≥90% or greater reduction in serum M-component plus urine M-component <100 mg per 24h and if only measurable non-bone marrow parameter was FLC,≥90% or greater reduction in difference from involved and uninvolved FLC levels. PR:≥50% reduction of serum M-protein or reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24h or if FLC, ≥50% decrease in the difference between involved and uninvolved FLC levels or ≥50% reduction in bone marrow plasma cells is required in place of M-protein, provided baseline percentage was ≥30%, and ≥50% reduction in the size of soft tissue plasmacytomas
- Progression-free Survival [ Time Frame: Every 28 day cycle(up to 10 cycles) then follow-up for up to 2 years ]
- Overall Survival [ Time Frame: Every 28 day cycle(up to 10 cycles) then follow-up for up to 2 years ]
|Study Start Date:||February 2010|
|Study Completion Date:||November 2014|
|Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive oral aurora A kinase inhibitor MLN8237 once daily on days 1-14 and bortezomib IV on days 1, 4, 8 and 11.
Drug: Aurora A kinase inhibitor MLN8237
Other Name: MLN8237Drug: bortezomib
I. To determine the maximum tolerated doses (MTD) with the combination of MLN8237 and bortezomib. (Phase I) II. To describe the toxicities associated with the combination of MLN8237 and bortezomib. (Phase I) III. To evaluate the overall response rate to the combination of MLN8237 and bortezomib in patients with relapsed or refractory multiple myeloma. (Phase II)
I. To assess progression-free survival in patients treated with this combination. (Phase II)
II. To assess overall survival in patients treated with this combination.(Phase II)
OUTLINE: This is a phase I dose escalation study followed by a phase II study. Patients receive oral aurora kinase inhibitor MLN8237 once daily on days 1-14 and bortezomib IV on days 1, 4, 8 and 11. Treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment all patients are followed every 2 months for 1 year and then every 3 months for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01034553
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|United States, California|
|University of California, San Francisco|
|San Fransisco, California, United States, 94143|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, Ohio|
|Ohio State University|
|Columbus, Ohio, United States, 43210|
|Study Chair:||Alexander K. Stewart, M.D.||Mayo Clinic|
|Principal Investigator:||Shaji K. Kumar, M.D.||Mayo Clinic|