Overview

This trial is active, not recruiting.

Condition multiple myeloma
Treatments ixazomib + lenalidomide + dexamethasone, placebo + lenalidomide + dexamethasone
Phase phase 3
Target proteasome
Sponsor Millennium Pharmaceuticals, Inc.
Start date May 2013
End date June 2018
Trial size 701 participants
Trial identifier NCT01850524, 163325, 2013-000326-54, C16014, U1111-1158-2646

Summary

This is a phase 3, randomized, double-blind, multicenter study to evaluate the safety and efficacy of IXAZOMIB versus placebo when added to lenalidomide and dexamethasone (LenDex) in patients with Newly Diagnosed Multiple Myeloma (NDMM) who are not eligible for stem cell transplant.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Active Comparator)
IXAZOMIB + Lenalidomide + Dexamethasone
ixazomib + lenalidomide + dexamethasone
Patients will receive single oral dose of IXAZOMIB (4.0mg) on days 1,8,15 and single oral dose of Lenalidomide (25mg) on days 1-21 and single oral dose of Dexamethasone (40mg) on days 1,8, 15 and 22 every 28 days for the first 18 cycles or until progressive disease or unacceptable toxicity, whichever comes first. After cycle 18 IXAZOMIB and Lenalidomide will be reduced and Dexamethasone will be discontinued.
(Placebo Comparator)
Placebo + Lenalidomide + Dexamethasone
placebo + lenalidomide + dexamethasone
Patients will receive single oral dose of Placebo on days 1,8,15 and single oral dose of Lenalidomide (25mg) on days 1-21 and single oral dose of Dexamethasone (40mg) on days 1,8, 15 and 22 every 28 days for the first 18 cycles or until progressive disease or unacceptable toxicity, whichever comes first. After cycle 18 IXAZOMIB and Lenalidomide will be reduced and Dexamethasone will be discontinued.

Primary Outcomes

Measure
Progression free survival (PFS)
time frame: PFS will be assessed at every cycle during the treatment period and subsequently every 4 weeks until disease progression (median length of the endpoint assessment period is projected to be approximately 30 months).

Secondary Outcomes

Measure
Complete Response (CR)
time frame: Response assessments will occur every cycle during the treatment period and subsequently every 4 weeks during the PFS follow-up period until disease progression (median length of the endpoint assessment period is projected to be approximately 30 months).
Pain response rate as assessed by the BPI-SF and analgesic use
time frame: BPI-SF will be assessed at every cycle during the treatment period and subsequently every 4 weeks during the PFS follow-up period until disease progression (median length of the endpoint assessment period is projected to be approximately 30 months).
Overall Survival (OS)
time frame: OS will be assessed at every cycle during the treatment period and subsequently every 4 weeks until disease progression and thereafter every 12 weeks until death or study termination (approximate length of the overall survival period is 60 month)

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Male or female patients 18 years or older diagnosed with Multiple Myeloma according to standard criteria who have not received prior treatment - Patients 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: 1. the patient is 65 years of age or older 2. the patient 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 patients 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 patients 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 - Patient is willing and able to adhere to the study visit schedule and other protocol requirements 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 lactating 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 psychiatric 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

Additional Information

Official title A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral IXAZOMIB (MLN9708) Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Takeda.