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

• Status: Completed
• Trial end date: 2014-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Treatments: Bortezomib

Criteria

Inclusion

• 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care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

• Total bilirubin =<1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x ULN, the direct bilirubin must be =< 2.0 mg/dL

• Measurable disease of multiple myeloma as defined by at least ONE of the following:

• Serum monoclonal protein >= 1.0 g/dL, >= 200 mg of monoclonal protein in the urine on 24 hour electrophoresis, serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio, monoclonal bone marrow plasmacytosis >= 30% (evaluable disease), or measurable plasmacytoma

• ECOG Performance Status (PS) 0, 1, or 2

• Hgb >= 9 g/dl

Exclusion

• 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

• Patient has >=Grade 2 peripheral neuropathy within 14 days before enrollment

• Patient has received other investigational drugs with 14 days before enrollment

• Diagnosed or treated for another malignancy within 2 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy

• Infection requiring systemic antibiotic therapy within 14 days preceding the first dose of study drug, or other severe infection

• Inability to swallow orally administered medication

• Prior allogeneic bone marrow or organ transplantation

• Patients who are currently receiving digoxin, cyclosporine, tacrolimus or sirolimus

• Severe cardiac comorbidity

• Known positive for HIV or active infectious hepatitis, type A, B or C