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A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral MLN9708 Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

Phase 3
Completed
Conditions
Kahler's disease
Multiple Myeloma (MM)
10035227
Registration Number
NL-OMON55577
Lead Sponsor
Millenium Pharmaceuticals
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
9
Inclusion Criteria

1.Multiple myeloma diagnosed according to standard criteria either
currently or at the time of initial diagnosis.
2.Patients must have measurable disease defined by at least 1 of the
following 3 measurements:
•Serum M-protein >= 1 g/dL (>= 10 g/L).
•Urine M-protein >= 200 mg/24 hours.
•Serum free light chain assay: involved free light chain level >=10 mg/dL
(>= 100 mg/L), provided that the serum free light chain ratio is abnormal.
3.Patients with relapsed and/or refractory MM who have received 1 to 3
prior therapies.
4.ECOG performance status of 0, 1, or 2.

Exclusion Criteria

1. Patient was refractory to lenalidomide or proteasome inhibitor-based therapy
at any line.
2. Female patients who are lactating or pregnant.
3. Failure to have fully recovered (ie, < Grade 1 toxicity) from the effects
of prior chemotherapy regardless of the interval since last treatment.
4. Major surgery within 14 days before randomization.
5. Radiotherapy within 14 days before randomization.
6. Central nervous system involvement.
7. Infection requiring systemic antibiotic therapy or other serious infection
within 14 days before randomization.
8. Diagnosis of Waldenstrom*s macroglobulinemia, POEMS (polyneuropathy,
organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes)
syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome,
or myeloproliferative syndrome.
9. Evidence of current uncontrolled cardiovascular conditions, including
uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic
congestive heart failure, unstable angina, or myocardial infarction within the
past 6 months.
10. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin,
ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin,
itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong
CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin,
phenobarbital), or use of Ginkgo biloba or St. John*s wort within 14 days
before randomization in the study.
11. Ongoing or active systemic infection, active hepatitis B virus infect,
active hepatitis C infection, or known human immunodeficiency virus (HIV)
positive.
12. Comorbid systemic illnesses or other severe concurrent disease which, in
the judgment of the investigator, would make the patient inappropriate for
entry into this study or interfere significantly with the proper assessment of
safety and toxicity of
the prescribed regimens.
13. Psychiatric illness/social situation that would limit compliance with study
requirements.

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>The primary endpoint is PFS, defined as the time from the date of randomization<br /><br>to the date of first documentation of disease progression based on central<br /><br>laboratory results and international myeloma working group (IMWG) criteria as<br /><br>evaluated by an independent review committee (IRC), or death due to any cause,<br /><br>whichever occurs first<br /><br>The endpoint has been met. Upon implementation of Amendment 8, evaluation of<br /><br>the safety profile of MLN9708 and/or LenDex is the only endpoint being<br /><br>assessed. Analysis of all other study endpoints will be complete at the final<br /><br>analysis and no further formal statistical analyses will be performed. However,<br /><br>the complete list of endpoints is retained for reference.</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>The key secondary endpoints are:<br /><br>• OS, measured as the time from the date of randomization to the date of death<br /><br>• OS in high-risk patients carrying del(17)<br /><br><br /><br>The endpoint has been met. Upon implementation of Amendment 8, evaluation of<br /><br>the safety profile of MLN9708 and/or LenDex is the only endpoint being<br /><br>assessed. Analysis of all other study endpoints will be complete at the final<br /><br>analysis and no further formal statistical analyses will be performed. However,<br /><br>the complete list of endpoints is retained for reference.</p><br>
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