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Trial record 1 of 1 for:    NCT01850524
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IXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01850524
Recruitment Status : Active, not recruiting
First Posted : May 9, 2013
Last Update Posted : October 20, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE April 26, 2013
First Posted Date  ICMJE May 9, 2013
Last Update Posted Date October 20, 2020
Actual Study Start Date  ICMJE May 17, 2013
Actual Primary Completion Date December 2, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2020)
Progression Free Survival (PFS) [ Time Frame: Up to 87 months ]
PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 6, 2013)
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). ]
PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease or death due to any cause, whichever occurs first.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2020)
  • Overall Survival (OS) [ Time Frame: 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.
  • Complete Response (CR) Rate [ Time Frame: 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.
  • Pain Response Rate as Assessed by the Brief Pain Inventory- Short Form (BPI-SF) and Analgesic Use [ Time Frame: 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. Brief Pain Inventory - Short Form (m-BPI-SF) is a participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable).
  • Overall Response Rate (ORR) [ Time Frame: Up to 27 months ]
    ORR is defined as the percentage of participants who achieved partial response (PR) or better relative to the ITT population during treatment period.
  • Time to Response [ Time Frame: Up to 27 months ]
    Time to response is defined as the time from the date of randomization to the first documentation of PR or better, as measured by IMWG criteria.
  • Duration of Response [ Time Frame: Up to 27 months ]
    Duration of response is measured as the time from the date of first documentation of PR or better to the date of first documented progression (PD) for responders, as measured by IMWG criteria.
  • Time to Progression (TTP) [ Time Frame: Up to 27 months ]
    Time to progression is defined as the time from randomization to the date of first documented disease progression.
  • Progression Free Survival (PFS)-2 [ Time Frame: Up to 87 months ]
    PFS2 is defined as the time from the date of randomization to the date of second documentation of disease progression (on subsequent line of anticancer therapy), as assessed by the investigator in accordance with IMWG criteria, or death due to any cause, whichever occurs first.
  • Percentage of Participants with Eastern Cooperative Oncology Group (ECOG) Performance Score [ Time Frame: Up to 27 months ]
    Eastern Cooperative Oncology Group (ECOG) scale score ranged from 0 to 5, where 0 indicated normal activity and 5 indicated death.
  • Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From the first dose of study drug through 30 days after administration of the last dose of study drug (Up to 28 months) ]
    An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent.
  • Percentage of Participants with Abnormal Laboratory Values [ Time Frame: From the first dose of study drug through 30 days after administration of the last dose of study drug (Up to 28 months) ]
    The laboratory evaluations will include hematology, clinical chemistry and urinalysis.
  • Change from Baseline in Health-Related Quality of Life (HRQOL) Measured by European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ)-C30 Scale Total Score [ Time Frame: Baseline to Month 27 ]
    EORTC-QLQ-C30 scale is used to assess HRQOL in cancer participants and contains 30 items. Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status scale, higher scores represent better HRQOL; whereas for the symptom scales lower scores represent better HRQOL.
  • Change from Baseline in HRQOL Measured by EORTC-QLQ)-MY20 Scale [ Time Frame: Baseline to Month 27 ]
    EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. The scale has 20 questions. Raw scores are averaged, and transformed to 0-100 scale, where higher score is better quality of life.
  • OS in High-risk Population Carrying del(17p), amp(1q21), t(4;14), or t(14;16) Mutations [ Time Frame: 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, as assessed in high-risk population carrying del(17p), amp(1q21), t(4;14), or t(14;16) mutations.
  • PFS in High-risk Population Carrying del(17p), amp(1q21), t(4;14), or t(14;16) Mutations [ Time Frame: Up to 87 months ]
    PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease based on central laboratory results and IMWG criteria as evaluated by an independent review committee (IRC) or death due to any cause, whichever occurs first, as assessed in high-risk population carrying del(17p), amp(1q21), t(4;14), or t(14;16) mutations.
  • Percentage of Participants with MRD-Negative Status as Assessed by Flow Cytometry [ Time Frame: Up to 27 months ]
    The absence of minimal residual disease (MRD negativity) will be tested in all participants who achieve a CR and maintained it until Cycle 18, using bone marrow aspirates. The frequency of MRD negativity, in each treatment arm will be determined, and its association with TTP, PFS, and OS will be evaluated.
  • Time to Pain Progression [ Time Frame: Up to 27 months ]
    Time to pain progression will be assessed as the time from randomization to the date of initial progression classification. Pain progression is defined as the occurrence of 1 of the following and confirmed by 2 consecutive evaluations (To qualify as progression, the participant must have a BPI-SF worst pain score > 4 during pain progression): 1) a ≥ 2 point and 30% increase from Baseline in BPI-SF worst pain score without an increase in analgesic use, or 2) a 25% or more increase in analgesic use from Baseline without a decrease in BPI-SF worst pain score from Baseline. Brief Pain Inventory - Short Form (m-BPI-SF) is a participant rated 11-point Likert rating scale ranged from 0 (no pain) to 10 (worst pain imaginable).
  • Cmax: Maximum Plasma Concentration for IXAZOMIB and its Metabolite MLN2238 [ Time Frame: Cycle 1, Day 1 at multiple time points (up to 4 hours) post-dose and Day 14 at any time; Cycle 2-3, Day 1 pre-dose and Day 14 at any time; Cycles 4-12 pre-dose (Cycle length is 28 days) ]
  • Percentage of Participants with New or Worsening of Existing Skeletal-related Events (SREs) [ Time Frame: Baseline and up to Month 27 ]
    SRE is defined as new fractures [including vertebral compression fractures]), irradiation of or surgery on bone, or spinal cord compression).
Original Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2013)
  • 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). ]
    Standard multiple myeloma disease assessment
  • Pain response rate as assessed by the BFI-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) ]
    OS is defined as the time from the date of randomization to the date of death.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE IXAZOMIB Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Newly Diagnosed Multiple Myeloma
Official Title  ICMJE 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 Newly Diagnosed Multiple Myeloma
Brief Summary The purpose of this study is to provide continued access to ixazomib and/or lenalidomide to participants who are continuing to have clinical benefit and to continue collecting relevant safety data to monitor safety in participants with Newly Diagnosed Multiple Myeloma (NDMM) who are not eligible for stem cell transplant.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: IXAZOMIB
    IXAZOMIB capsules.
    Other Name: MLN9708
  • Drug: Placebo
    IXAZOMIB matching-placebo capsules.
  • Drug: Dexamethasone
    Dexamethasone tablets.
  • Drug: Lenalidomide
    Lenalidomide capsules.
Study Arms  ICMJE
  • Active Comparator: IXAZOMIB

    IXAZOMIB 4.0 mg capsules orally once on Days 1,8,15 and lenalidomide 25 mg capsules orally on Days 1-21 and dexamethasone 40 mg tablets orally on Days 1,8, 15 and 22, during every 28-day cycle, for the first 18 cycles or until progressive disease or unacceptable toxicity, whichever occurs first.

    After cycle 18 IXAZOMIB and Lenalidomide will be reduced and Dexamethasone will be discontinued.

    Interventions:
    • Drug: IXAZOMIB
    • Drug: Dexamethasone
    • Drug: Lenalidomide
  • Placebo Comparator: Placebo

    IXAZOMIB matching-placebo capsules orally once on Days 1,8,15 and lenalidomide 25 mg capsules orally on days 1-21 and dexamethasone 40mg tablets orally on Days 1,8, 15 and 22, during every 28-day cycle for the first 18 cycles or until progressive disease or unacceptable toxicity, whichever occurs first.

    After cycle 18 IXAZOMIB and Lenalidomide will be reduced and Dexamethasone will be discontinued.

    Interventions:
    • Drug: Placebo
    • Drug: Dexamethasone
    • Drug: Lenalidomide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 6, 2013)
701
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 28, 2022
Actual Primary Completion Date December 2, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female participants 18 years or older diagnosed with Multiple Myeloma according to standard criteria who have not received prior treatment for multiple myeloma.
  2. 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:

    • The participant is 65 years of age or older.
    • The 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.
  3. Measurable disease as specified in study protocol.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  5. Meet the clinical laboratories criteria as specified in the protocol.
  6. 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.
  7. 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.
  8. Suitable venous access for the study-required blood sampling.
  9. Must be able to take concurrent aspirin 70 mg to 325 mg daily (or enoxaparin if aspirin allergic).
  10. Voluntary written consent.
  11. Participant is willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

  1. Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen.
  2. Diagnosed and treated for another malignancy within 5 years before randomization or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
  3. Inability or unwillingness to receive antithrombotic therapy.
  4. Female participants who are lactating or pregnant.
  5. Major surgery or radiotherapy within 14 days before randomization.
  6. Infection requiring intravenous antibiotics within 14 days before the first dose of study drug.
  7. Central nervous system involvement.
  8. Diagnosis of Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
  9. Evidence of current uncontrolled cardiovascular conditions within 6 months prior to randomization, including: Uncontrolled hypertension, cardiac arrhythmias, or congestive heart failure; Unstable angina, or Myocardial infarction.
  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. Active hepatitis B or C virus 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 participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (e.g., peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause).
  13. Psychiatric illness/social situation that would limit compliance with study requirements.
  14. Known allergy to any of the study medications.
  15. 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.
  16. Treatment with any investigational products within 60 days before randomization.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Korea, Republic of,   New Zealand,   Russian Federation,   United States
Removed Location Countries Japan,   United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT01850524
Other Study ID Numbers  ICMJE C16014
2013-000326-54 ( EudraCT Number )
U1111-1158-2646 ( Registry Identifier: WHO )
163325 ( Registry Identifier: HC-CTD )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
URL: https://vivli.org/ourmember/takeda/
Responsible Party Takeda ( Millennium Pharmaceuticals, Inc. )
Study Sponsor  ICMJE Millennium Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Clinical Science Millennium Pharmaceuticals, Inc.
PRS Account Takeda
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP