Aurora A Kinase Inhibitor MLN8237 and Bortezomib in Treating Patients With Relapsed or Refractory Multiple Myeloma

Phase 1

Completed

• Conditions: Refractory Multiple Myeloma
• Interventions: Drug: Aurora A kinase inhibitor MLN8237; Drug: bortezomib

• Registration Number: NCT01034553
• Lead Sponsor: Mayo Clinic

Brief Summary

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.

Detailed Description

PRIMARY OBJECTIVES:

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)

SECONDARY OBJECTIVE:

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2009-12-16
• Study First Submitted QC: 2009-12-16
• Study First Posted: 2009-12-17
• Study Start: 2010-02
• Primary Completion: 2014-09
• Study Completion: 2014-11
• Results First Submitted: 2015-10-16
• Status Verified: 2016-02
• Results First Submitted QC: 2016-04-18
• Last Update Submitted: 2016-04-18
• Results First Posted: 2016-05-25
• Last Update Posted: 2016-05-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	Aurora A kinase inhibitor MLN8237	Patients receive oral aurora A kinase inhibitor MLN8237 once daily on days 1-14 and bortezomib IV on days 1, 4, 8 and 11.
Arm I	bortezomib	Patients receive oral aurora A kinase inhibitor MLN8237 once daily on days 1-14 and bortezomib IV on days 1, 4, 8 and 11.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate to the Combination of MLN8237 and Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma.	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
Dose-limiting Toxicity (DLT) (Phase I)	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.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival	Every 28 day cycle(up to 10 cycles) then follow-up for up to 2 years
Overall Survival	Every 28 day cycle(up to 10 cycles) then follow-up for up to 2 years

Trial Locations

Locations (6)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Mayo Clinic in Arizona; 🇺🇸 Scottsdale, Arizona, United States

University of California, San Francisco; 🇺🇸 San Fransisco, California, United States