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

NCT01034553 | Completed Phase 1 Results DMC

• 4 other identifiers: MC088ANCI-2009-0147508-006317X14003
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 6

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.

Conditions

Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Dose-limiting Toxicity (DLT) (Phase I)

  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.

  28 days

• Overall Response Rate to the Combination of MLN8237 and Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma.

  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

  Every 28 day cycle(up to 10 cycles)

Secondary Outcomes (2)

• 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

Study Arms (1)

Arm I

EXPERIMENTAL

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; Drug: bortezomib

Interventions

Aurora A kinase inhibitor MLN8237 DRUG

Given orally

Also known as: MLN8237

Arm I

bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, PS-341, VELCADE

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ANC \>= 1500/uL
• AST =\< 2.5 x ULN
• Creatinine =\< 1.5 x ULN
• Creatinine clearance as calculated by the method of Cockroft and Gault \>= 30 mL/minute
• Patients with relapsed or refractory multiple myeloma requiring treatment
• Patients who have received prior bortezomib therapy will be allowed on trial as long as they did not progress during bortezomib or =\< 60 days of therapy discontinuation
• Negative serum pregnancy test done =\< 7 days prior to registration, for women of childbearing potential (WOCBP) only (a WOCBP is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months)
• Willingness to return to enrolling institution for follow-up
• Life expectancy \>= 12 weeks
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
• Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study
• Male subject agrees to use an acceptable method for contraception for the duration of the study
• Patients have a baseline LVEF \>= 45% at baseline
• Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
• PLT \>= 100,000/uL

You may not qualify if:

• Major surgery, open biopsy (excluding bone marrow) or significant traumatic injury =\< 4 weeks prior to registration
• Melphalan or other myelosuppressive agents including lenalidomide and non-myelosuppressive agents such as thalidomide or high dose corticosteroids =\< 2 weeks prior to registration
• Concurrent use of corticosteroids, but patients may be on chronic steroids (maximum dose 20 mg/day prednisone equivalent) if they are being given for disorders other than myeloma, i.e., adrenal insufficiency, rheumatoid arthritis, etc
• Uncontrolled infection
• Pregnant women or women of reproductive ability who are unwilling to use effective contraception
• Nursing women
• Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 4 weeks after stopping treatment
• Other co-morbidity or psychiatric illness which would interfere with patient's ability to participate in this trial
• Recent history of myocardial infarction in the six months prior to registration
• Uncontrolled angina or electrocardiographic evidence of acute ischemia
• Severe uncontrolled ventricular arrhythmias or electrocardiographic evidence of active conduction system abnormalities
• Cardiac amyloidosis with hypotension (systolic BP less than 100mmHg)
• MGUS or smoldering myeloma
• Serious non-healing wound, or ulcer
• Known hypersensitivity to Bortezomib, boron or mannitol

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (6)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

MLN 8237; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Alexander Keith Stewart, M.B.CH.B
• Organization: Mayo Clinic

stewart.keith@mayo.edu

(480)301-4411

Study Officials

• Alexander K. Stewart, M.D.

  Mayo Clinic

  STUDY CHAIR

• Shaji K. Kumar, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2009
• First Posted: December 17, 2009
• Study Start: February 1, 2010
• Primary Completion: September 1, 2014
• Study Completion: November 1, 2014
• Last Updated: May 25, 2016
• Results First Posted: May 25, 2016

Record last verified: 2016-02

Locations

US (6)