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Refractory Multiple MyelomaPhase 1/2NCT01034553

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

A Phase 1/2 study testing Aurora A kinase inhibitor MLN8237 and bortezomib in people with Refractory Multiple Myeloma, run by Mayo Clinic at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Refractory Multiple Myeloma
What is being tested?
Aurora A kinase inhibitor MLN8237 and bortezomib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
6 sitesUnited States
Study dates
Feb 2010to Nov 2014
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Ohio State University

    Columbus, Ohio, 43210

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • University of California, San Francisco

    San Francisco, California, 94143

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Phase I/II Study of Combination of Aurora Kinase Inhibitor MLN8237 and Bortezomib in 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
Aurora A kinase inhibitor MLN8237, bortezomib
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Aurora A kinase inhibitor MLN8237Drug

    Also called MLN8237

    Given orally

  • bortezomibDrug

    Also called LDP 341, MLN341, PS-341, VELCADE

    Given IV

Study groups in NCT01034553
Study groupRoleWhat they receive
Arm IExperimentalPatients receive oral aurora A kinase inhibitor MLN8237 once daily on days 1-14 and bortezomib IV on days 1, 4, 8 and 11.
Receives: Drug: Aurora A kinase inhibitor MLN8237; Drug: bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 28 days

  2. 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

    Measured: Every 28 day cycle(up to 10 cycles)

Secondary outcomes (2)

  1. Progression-free Survival

    Measured: Every 28 day cycle(up to 10 cycles) then follow-up for up to 2 years

  2. Overall Survival

    Measured: Every 28 day cycle(up to 10 cycles) then follow-up for up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Dec 2009 (estimated)
  2. Study startFeb 2010
  3. Primary completionSep 2014
  4. Study completionNov 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01034553
Sponsor's protocol ID
MC088A
Other IDs
NCI-2009-01475, 08-006317, X14003, MC088A
Status last verified
Feb 2016
First submitted
16 Dec 2009
Last updated
25 May 2016
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Aurora A kinase inhibitor MLN8237 and bortezomib in people with Refractory Multiple Myeloma, run by Mayo Clinic at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 May 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting Toxicity (DLT) (Phase I) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01034553.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2016.

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