Newly-diagnosed multiple myeloma (NDMM)
Conditions
Interventions
investigational material(s)
Generic name etc : MLN9708
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational material
Sponsors
Takeda Pharmaceutical Company Limited
Millennium Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female participants 18 years or older diagnosed with Multiple Myeloma according to standard criteria who have not received prior treatment - Participants for whom lenalidomide and dexamethasone treatment is appropriate and who are not eligible for high-dose therapy followed by stem-cell transplantation (HDT-SCT) for 1 or more of the following reasons: i. Participant is 65 years of age or older ii.Participant is less than 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT - Measurable disease as specified in study protocol - Eastern Cooperative Oncology Group (ECOG)performance status of 0 to 2 - Meet the clinical laboratories criteria as specified in the protocol - Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence, and must also agree to ongoing pregnancy testing; must also adhere to the guidelines of the lenalidomide pregnancy prevention program - Male participants who agree to practice effective barrier contraception or agree to practice true abstinence AND must adhere to the guidelines of the lenalidomide pregnancy prevention program - Suitable venous access for the study-required blood sampling - Must be able to take concurrent aspirin 70mg to 325 mg daily (or enoxaparin if aspirin allergic) - Voluntary written consent - Participant is willing and able to adhere to the study visit schedule and other protocol requirements
Exclusion criteria
Exclusion criteria: - Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen - Diagnosed and treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection - Inability or unwillingness to receive antithrombotic therapy - Female patients who are breast feeding or pregnant - Major surgery or radiotherapy within 14 days before randomization - Infection requiring intravenous antibiotics within 14 days before the first dose of study drug - Central nervous system involvement - Diagnosis of Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome - Evidence of current uncontrolled cardiovascular conditions - 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 - Active hepatitis B or C virus infection, or known human immunodeficiency virus(HIV) positive - 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 (eg, peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause) - Serious medical or illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol - Known allergy to any of the study medications - Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment - Treatment with any investigational products within 60 days before the first dose of the study drug regimen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1.Efficacy: Progression-free survival (PFS) Timeframe: Up to approximately 79 months PFS was defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause according to International Myeloma Working Group (IMWG) criteria whichever occurs first. PD required one of the following: Increase of >=25% from nadir in: Serum M-component and/or (the absolute increase must be >=0.5 g/dL); Urine M-component and/or (the absolute increase must be >=200 mg/24 hours); in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase must be > 10 mg/dL); Bone marrow plasma cell percentage: the absolute % must be >10%; development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas; hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.85 mmol/L). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.Overall Survival (OS) Timeframe: From the date of randomization to death due to any cause (Up to 87 months) OS is defined as the time from the date of randomization to the date of death. Participants without documented death at the time of analysis are censored at the date last known to be alive. 2.Complete Response (CR) Rate Timeframe: Up to 27 months CR rate is defined as the percentage of participants who achieve CR assessed by an IRC relative to the intent-to-treat (ITT) population during the treatment period. Percentage of participants with CR, as assessed by IMWG disease assessment criteria will be reported. CR was defined as disappearance of all target lesions. 3.Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use Timeframe: Up to 27 months: Pain response rate is defined as percentage of participants with pain response. Pain response is defined as the occurrence of at least a 30% reduction from baseline in BPI-SF worst pain score over the last 24 hours without an increase in analgesic use for 2 consecutive measurements > 28 days apart, will be reported. BPI-SF is a participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable). 4.-7. Overall Response Rate (ORR), Time to Response, Duration of Response, and Time to Progression (TTP) Timeframe: Up to 27 months: ORR was defined as the percentage of participants who achieved CR+ partial response (PR)+ very good partial response (VGPR) (including sCR) or better relative to the ITT population during treatment period. PR was defined as at least a 30% decrease in sum of diameters (SoD) of target lesions, taking as reference baseline SoD. VGPR is disappearance of any soft tissue plasmacytomas present at baseline and no new plasmacytomas. sCR was defined as stringent complete response. Time to response was defined as the time from the date of randomization to the first documentation of PR or better, as measured by IMWG criteria. Du | — |
Countries
Japan, Refer to "Other"section
Outcome results
None listed