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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. )

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: IXAZOMIB Drug: Placebo Drug: Dexamethasone Drug: Lenalidomide Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 701 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 17, 2013
Actual Primary Completion Date : December 2, 2019
Estimated Study Completion Date : February 28, 2022


Arm Intervention/treatment
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.

Drug: IXAZOMIB
IXAZOMIB capsules.
Other Name: MLN9708

Drug: Dexamethasone
Dexamethasone tablets.

Drug: Lenalidomide
Lenalidomide capsules.

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.

Drug: Placebo
IXAZOMIB matching-placebo capsules.

Drug: Dexamethasone
Dexamethasone tablets.

Drug: Lenalidomide
Lenalidomide capsules.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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).

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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).

  18. 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) ]
  19. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01850524


Locations
Show Show 148 study locations
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Director Clinical Science Millennium Pharmaceuticals, Inc.
Additional Information:
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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01850524    
Other Study ID Numbers: C16014
2013-000326-54 ( EudraCT Number )
U1111-1158-2646 ( Registry Identifier: WHO )
163325 ( Registry Identifier: HC-CTD )
First Posted: May 9, 2013    Key Record Dates
Last Update Posted: October 20, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Newly Diagnosed multiple myeloma
multiple myeloma
MLN9708
IXAZOMIB
Proteasome inhibitor
Tourmaline MM2
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Lenalidomide
Ixazomib
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors