To determine whether the addition of oral ixazomib to the background therapy of lenalidomide and dexamethasone improves progression-freesurvival (PFS) in patients with relapsed and/or refractory multiple myeloma (RRMM) The objective has been met.…
ID
Source
Brief title
Condition
- Plasma cell neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is PFS, defined as the time from the date of randomization
to the date of first documentation of disease progression based on central
laboratory results and international myeloma working group (IMWG) criteria as
evaluated by an independent review committee (IRC), or death due to any cause,
whichever occurs first
The endpoint has been met. Upon implementation of Amendment 8, evaluation of
the safety profile of MLN9708 and/or LenDex is the only endpoint being
assessed. Analysis of all other study endpoints will be complete at the final
analysis and no further formal statistical analyses will be performed. However,
the complete list of endpoints is retained for reference.
Secondary outcome
The key secondary endpoints are:
• OS, measured as the time from the date of randomization to the date of death
• OS in high-risk patients carrying del(17)
The endpoint has been met. Upon implementation of Amendment 8, evaluation of
the safety profile of MLN9708 and/or LenDex is the only endpoint being
assessed. Analysis of all other study endpoints will be complete at the final
analysis and no further formal statistical analyses will be performed. However,
the complete list of endpoints is retained for reference.
Background summary
Multiple myeloma (MM) is a clonal disease of plasma cells that is characterized
by the accumulation of plasma cells in the bone marrow (and other organs) and
sometimes results in bone marrow failure, bone destruction, hypercalcemia, and
renal failure.
Although MM is uniformly fatal, survival has improved over the last 2 decades
because of newer and more effective treatment options. Multiple myeloma is
sensitive to a number of cytotoxic drugs such as alkylating agents,
anthracyclines, and corticosteroids for initial treatment and for relapsed
disease.
Despite the increase in the number of therapeutic options, the disease remains
incurable and there is a need for new and better agents. Patients who relapse
after their initial therapy demonstrate variable response to subsequent
treatments with decreasing likelihood and duration of response (DOR). Patients
ultimately become refractory to approved therapies and have no alternative
treatment options. In an effort to further target the proteasome with improved
activity in MM and other cancers, Millennium has developed ixazomib citrate.
Study objective
To determine whether the addition of oral ixazomib to the background therapy
of lenalidomide and dexamethasone improves progression-free
survival (PFS) in patients with relapsed and/or refractory multiple myeloma
(RRMM)
The objective has been met. Upon implementation of Amendment 8, the objective
is to continue to collect long-term safety data from patients
who are continuing on ixazomib (MLN9708) and LenDex or LenDex (note the placebo
capsule will be discontinued) because of continuing clinical
benefit. Data collection for all other study objectives will be complete at the
time of the final analysis and no further formal analyses will be
conducted. The original lists of objectives are retained for reference only.
Study design
randomized, double-blind, placebo-controlled study
Intervention
Ixazomib citrate Plus Lenalidomide and Dexamethasone Versus Placebo Plus
Lenalidomide and Dexamethasone
Patients will receive study drug (ixazomib citrate 4.0 mg or matching placebo
capsule) on Days 1, 8, and
15 plus lenalidomide (25 mg) on Days 1 through 21 and dexamethasone (40 mg) on
Days 1, 8, 15,
and 22 of a 28-day cycle. Patients may continue to receive treatment until PD
or unacceptable
toxicity, whichever comes first. Dose modifications may be made based on
toxicities. Patients with
creatinine clearance of 30 to 50 mL/min will receive a reduced lenalidomide
dose of 10 mg once
daily on Days 1 through 21 of a 28-day cycle. The lenalidomide dose may be
escalated to 15 mg
once daily after 2 cycles if the patient is not responding to treatment and is
tolerating the treatment.
Study burden and risks
Additional tests/assessments related to study participation are:
• questionnaires and review of status;
• elektrocardiogram (ecg);
• farmacokinetic bloodsamples;
• patient diary.
Based on studies in an early stage with patients treated with ixazomib citrate,
the following discomforts and risks could occur:
• a low numer of platelets (an increase of the chance of bleedings);
• skin rash, which can vary from a few red spots that may or may not itch or
spots over the entire body;
• vfatigue or weakness, nausea, vomiting, diarrheae.
Landsdowne Street Cambridge 40
MA 02139
US
Landsdowne Street Cambridge 40
MA 02139
US
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005496-17-NL |
| ClinicalTrials.gov | NCT01564537 |
| CCMO | NL40132.018.12 |