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Relapsed Multiple MyelomaPhase 3NCT01564537

A Phase 3 Study Comparing Oral Ixazomib Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma

A Phase 3 study testing Ixazomib, Lenalidomide and Dexamethasone in people with Relapsed Multiple Myeloma and Refractory Multiple Myeloma, run by Takeda at 24 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to determine whether the addition of oral ixazomib to the background therapy of lenalidomide and dexamethasone improves progression free survival (PFS) in participants with relapsed and/or refractory multiple myeloma (RRMM). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ixazomib, Lenalidomide and Dexamethasone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
722 participants
Where
24 sitesin 2 countries
Study dates
1 Aug 2012to 8 Feb 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female participants 18 years of age or older.
  • Multiple myeloma diagnosed according to standard criteria either currently or at the time of initial diagnosis.
  • NOTE: The initial diagnosis must have been symptomatic multiple myeloma, although the relapsed disease did not need to be symptomatic.
  • Must have had 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.
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  • Serum free light chain (FLC) assay: involved FLC level ≥ 10 mg/dL (≥ 100 mg/L), provided that the serum FLC ratio was abnormal.
  • Participants with relapsed and/or refractory multiple myeloma (RRMM) who had received 1 to 3 prior therapies.
  • NOTE: population included the following 3 categories of participants:
  • Participants who relapsed from their previous treatment(s) but were not refractory to any previous treatment.
  • Participants who were refractory to all lines of previous treatment(s) (ie, participants who had never responded to any therapies received).
  • Participants who relapsed from at least 1 previous treatment AND additionally were refractory to at least 1 previous treatment. For the purposes of this study, refractory disease was defined as disease progression on treatment or progression within 60 days after the last dose of a given therapy.
  • A line of therapy was defined as 1 or more cycles of a planned treatment program. This may have consisted of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation, followed by maintenance was considered 1 line of therapy. Autologous and allogenic transplants were permitted.
  • Must have met the following clinical laboratory criteria:
  • Absolute neutrophil count (ANC) ≥ 1000/mm^3 and platelet count ≥ 75,000/mm^3. Platelet transfusions to help participants meet eligibility criteria were not allowed within 3 days prior to randomization.
  • Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN.
  • Calculated creatinine clearance ≥ 30 mL/min NOTE: Participants with a low creatinine clearance ≤ 60 mL/min (or ≤ 50 mL/min, according to lenalidomide prescribing information/local practice) were to receive a reduced lenalidomide dose of 10 mg once daily (QD) on Days 1 through 21 of a 28-day cycle. The lenalidomide dose may have been escalated to 15 mg QD after 2 cycles if the participant was not responding to treatment and was tolerating the treatment. If renal function normalized (ie, creatinine clearance >60 mL/min or >50 mL/min, according to lenalidomide prescribing information/local practice) and the participant continued to tolerate this treatment, lenalidomide may then have been escalated to 25 mg QD.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Participants who received prior allogenic transplant must have had no active graft-versus-host disease.
  • Female participants who:
  • Were postmenopausal for at least 24 months before the screening visit, OR
  • Were surgically sterile, OR
  • If they were of childbearing potential must have: had a negative pregnancy test with a sensitivity of at least 25 mIU/mL within 10 to 14 days and again within 24 hours prior to starting Cycle 1 of lenalidomide; either agreed to practice true abstinence, when this was in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal were not acceptable methods of contraception.) OR begun 2 reliable methods of birth control (1 highly effective method and 1 additional effective method) at the same time, at least 28 days before starting study treatment through 90 days after the last dose of study treatment; and agreed to ongoing pregnancy testing AND must have also adhered to the guidelines of the RevAssist program (US participants), RevAid program (Canadian participants), iAccess program (Australian participants), RevMate program (Japanese participants) or The Lenalidomide Pregnancy Risk Minimisation Plan as outlined in the Study Manual (all other participants who were not using commercial supplies).
  • Male patients, even if surgically sterilized (ie, status postvasectomy), who:
  • Agreed to practice true abstinence, when this was in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal were not acceptable methods of contraception.) OR
  • Agreed to practice effective barrier contraception during the entire study treatment period and 90 days after the last dose of study treatment if their partner was of childbearing potential, even if they had a successful vasectomy, AND
  • Must have also adhered to the guidelines of the RevAssist program (US participants), RevAid program (Canadian participants), iAccess program (Australian participants), RevMate program (Japanese participants) or The Lenalidomide Pregnancy Risk Minimisation Plan as outlined in the study Manual (all other participants who were not using commercial supplies)
  • Must have been able to take concurrent aspirin 81 to 325 mg daily (or enoxaparin 40 mg subcutaneously daily [or its equivalent] if allergic to aspirin), per published standard or institutional standard of care, as prophylactic anticoagulation.
  • NOTE: For participants with prior history of deep vein thrombosis (DVT), low-molecular-weight heparin (LMWH) was mandatory.
  • Voluntary written consent must have been given before performance of any study related procedure not part of standard medical care, with the understanding that consent may have been withdrawn by the participant at any time without prejudice to future medical care.
  • Was willing and able to adhere to the study visit schedule and other protocol requirements.

Who cannot join

  • Was refractory to lenalidomide or proteasome inhibitor-based therapy at any line.
  • NOTE: Refractory disease was defined as disease progression on treatment or progression within 60 days after the last dose of a given therapy. Participants who progressed after 60 days from the last dose of a given therapy were considered relapsed and were eligible for inclusion in the study.
  • Participants who were refractory to thalidomide-based therapy were eligible.
  • Female participants who were breast feeding or pregnant.
  • Failure to have fully recovered (ie, Grade 1 toxicity) from the effects of prior chemotherapy (except for alopecia) regardless of the interval since last treatment.
  • Major surgery within 14 days before randomization.
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  • Radiotherapy within 14 days before randomization.
  • Central nervous system involvement.
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days before randomization.
  • 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.
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within 6 months before randomization in the study.
  • Systemic treatment with strong inhibitors of cytochrome P450 (CYP) 1A2 (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.
  • Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus positive.
  • 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 (eg, peripheral neuropathy that is Grade 1 with pain or Grade 2 or higher of any cause).
  • Psychiatric illness/social situation that would limit compliance with study requirements.
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
  • Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal condition that could interfere with the oral absorption or tolerance of treatment.
  • Diagnosed or treated for another malignancy within 2 years before randomization or previously diagnosed with another malignancy and any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type were not excluded if they had undergone complete resection.

Trial locations and contacts

24 sites in 2 countries.

24 sites in 2 countries

United States18 sites

  • Pacific Cancer Medical Center Inc

    Anaheim, California, 92801

  • West Contra Costa Healthcare District

    Berkeley, California, 94704

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 2215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • MUSC Hollings Cancer Center

    Charleston, South Carolina, 29425

  • John H. Stroger, Jr. Hospital of Cook County

    Chicago, Illinois, 60612

  • Blood and Cancer Clinic

    Fayetteville, North Carolina, 28303

  • University of Florida

    Gainesville, Florida, 32610

  • Hackensack University Medical Center

    Hackensack, New Jersey, 7601

  • Cancer & Blood Disease Center

    Lecanto, Florida, 34461

  • University of Arkansas Medical Sciences

    Little Rock, Arkansas, 72205

  • Northwest Georgia Oncology Center

    Marietta, Georgia, 30060

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • West Virginia University Hospitals and Clinic

    Morgantown, West Virginia, 26506-9300

  • Columbia University Medical Center

    New York, New York, 10032

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Scranton Hematology Oncology

    Scranton, Pennsylvania, 18510

  • Fred Hutchinson Cancer Research

    Seattle, Washington, 98109

Other trials in United States

Canada6 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • CHUM Notre-Dame Hospital

    Montreal, Quebec, H2L 4M1

  • MUHC Glen Site Cedars Cancer Centre

    Montreal, Quebec, H4A 3J1

  • Saint John Regional Hospital

    Saint John, New Brunswick, E2L 4L2

  • Vancouver General Hospital

    Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

About this study

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 Relapsed and/or Refractory Multiple Myeloma

The purpose of this study is to determine whether the addition of oral ixazomib to the background therapy of lenalidomide and dexamethasone improves progression free survival (PFS) in participants with relapsed and/or refractory multiple myeloma (RRMM).

Read the detailed description

The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have relapsed and/or refractory multiple myeloma (RRMM). This study will look at progression free survival (PFS), overall survival (OS) and safety in participants who take ixazomib in addition to lenalidomide and dexamethasone compared to placebo in addition to lenalidomide and dexamethasone.

The study enrolled 722 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

  • Ixazomib 4 mg + lenalidomide + dexamethasone
  • Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient + lenalidomide + dexamethasone

All participants will receive treatment in 28 day cycles until disease progression or unacceptable toxicity.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 80 months. Participants will make multiple visits to the clinic, and will be contacted every 4 weeks for PFS and every 12 weeks for OS.

Being tested
Ixazomib, Lenalidomide, Dexamethasone, Placebo
Keywords
Drug therapy
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IxazomibDrug

    Also called MLN9708, NINLARO®

    Ixazomib capsules

  • LenalidomideDrug

    Lenalidomide capsules

  • DexamethasoneDrug

    Dexamethasone tablets

  • PlaceboDrug

    Ixazomib placebo-matching capsules

Study groups in NCT01564537
Study groupRoleWhat they receive
Ixazomib + Lenalidomide + DexamethasoneExperimentalIxazomib 4 mg, capsules, orally, once, on Days 1, 8 and 15; plus lenalidomide 25 mg, orally, once, on Days 1 through 21; and dexamethasone 40 mg, orally, once, on Days 1, 8, 15 and 22 of a 28-day cycle for multiple cycles until progressive disease (PD) or unacceptable toxicity, whichever occurred first up to end of treatment (EOT) up to approximately 42.9 months.
Receives: Drug: Ixazomib; Drug: Lenalidomide; Drug: Dexamethasone
Placebo + Lenalidomide + DexamethasonePlacebo comparatorIxazomib placebo-matching capsules, orally, once, on Days 1, 8 and 15; plus lenalidomide 25 mg, orally, once, on Days 1 through 21; and dexamethasone 40 mg, orally, once, on Days 1, 8, 15 and 22 of a 28-day cycle for multiple cycles until PD or unacceptable toxicity, whichever occurred first up to approximately 41 months.
Receives: Drug: Lenalidomide; Drug: Dexamethasone; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS) as Assessed by the Independent Review Committee (IRC)

    Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of first documentation of disease progression (PD) or death due to any cause, whichever occurs first. Response including PD was assessed by independent review committee (IRC) using the International Myeloma Working Group (IMWG) response criteria. PD requires 1 of the following: Increase of ≥ 25% from nadir in: Serum M-component (absolute increase ≥ 0.5 g/dl); Urine M-component (absolute increase ≥ 200 mg/24 hours); In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved free light chain (FLC) levels (absolute increase > 10 mg/dl); Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcemia (corrected serum calcium > 11.5 mg/dl) attributed solely to plasma cell proliferative disease. Status evaluated every 4 weeks until disease progression (PD) was confirmed.

    Measured: From date of randomization until disease progression or death up to approximately 27 months (approximate median follow-up 15 months)

Secondary outcomes (14)

  1. Overall Survival (OS)

    Overall survival is defined as the time from the date of randomization to the date of death. Participants without documentation of death at the time of the analysis were censored at the date when they were last known to be alive.

    Measured: From date of randomization until death (up to approximately 97 months)

  2. Overall Survival in High-Risk Participants Carrying Deletion 17 [Del(17)]

    Overall survival is defined as the time from the date of randomization to the date of death. The high-risk participants whose myeloma carried del(17) subgroup was defined as the cases reported as positive for del(17) by the central laboratory combined with those cases that lacked a central laboratory result but with known del (17) by local laboratory. Participants without documentation of death at the time of the analysis were censored at the date when they were last known to be alive. Data is only reported high-risk participants with Del(17).

    Measured: From the time of screening until disease progression and thereafter every 12 weeks until death or study termination (up to approximately 97 months)

  3. Overall Response Rate (ORR) as Assessed by the IRC

    ORR was defined as the percentage of participants with Complete Response (CR) including stringent complete response (sCR), very good partial response (VGPR) and Partial Response (PR) assessed by the IRC using IMWG criteria. Percentages are rounded off to single decimal.

    Measured: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months(approximate median follow-up 15 months)

  4. Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) as Assessed by the IRC

    Response was assessed by the IRC using International Myeloma Working Group (IMWG) Criteria. CR is defined as negative immunofixation on the serum and urine and; disappearance of any soft tissue plasmacytomas and; < 5% plasma cells in bone marrow. VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg per 24 hours. Percentages are rounded off to single decimal.

    Measured: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months (approximate median follow-up 15 months)

  5. Duration of Response (DOR)

    DOR was measured as the time in months from the date of first documentation of a confirmed response of PR or better (CR [including sCR] + PR+ VGPR) to the date of the first documented disease progression (PD) among participants who responded to the treatment. Response was assessed by the investigator using International Myeloma Working Group (IMWG) Criteria.

    Measured: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 38 months

  6. Time to Progression (TTP) as Assessed by the IRC

    TTP was measured as the time in months from the first dose of study treatment to the date of the first documented progressive disease (PD) as assessed by the IRC using IMWG criteria.

    Measured: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months (approximate median follow-up 15 months)

  7. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Eastern Cooperative Oncology Group (ECOG) performance score, laboratory values, vital sign measurements and reported adverse events (AEs) were collected and assessed to evaluate the safety of therapy throughout the study. An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.

    Measured: From the date of signing of the informed consent form through 30 days after the last dose of study drug up to approximately 115 months

  8. Number of Participants With Change From Baseline in Pain Response

    Pain response was defined as 30% reduction from Baseline in Brief Pain Inventory-Short Form (BPI-SF) worst pain score over the last 24 hours without an increase in analgesic (oral morphine equivalents) use at 2 consecutive evaluations. The BPI-SF contains 15 items designed to capture the pain severity ("worst," "least," "average," and "now" [current pain]), pain location, medication to relieve the pain, and the interference of pain with various daily activities including general activity, mood, walking activity, normal work, relations with other people, sleep, and enjoyment of life. The pain severity items are rated on a 0 to 10 scale where: 0=no pain and 10=pain as bad as you can imagine and averaged for a total score of 0 (best) to 10 (Worst).

    Measured: Baseline and end of treatment (EOT) (up to approximately 38 months)

  9. Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life (QOL) Questionnaire (EORTC-QLQ-C30)

    The EORTC-QLQ-C30 is a 30-question tool used to assess the overall quality of life in cancer participants. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact).The EORTC-QLQ-C30 Global Health Status/QOL Scale is scored between 0 and 100, where higher scores indicate better Global Health Status/QOL. Negative changes from baseline indicate deterioration in QOL or functioning and positive changes indicate improvement. Scores are linearly transformed to a 0-100 scale. High scores for the global and functional domains indicate higher quality of life or functioning. Higher scores on the symptom scales represent higher levels of symptomatology or problems.

    Measured: Baseline, EOT and follow-up (up to approximately 97 months)

  10. Change From Baseline in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Multiple Myeloma Module (QLQ-MY-20)

    The EORTC-QLQ-MY-20 is a patient-completed, 20-question quality of life questionnaire that has 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms and side-effects of treatment). The participant answers questions about their health during the past week using a 4-point scale where 1=Not at All to 4=Very Much. A negative change from Baseline indicates improvement. Scores are linearly transformed to a 0-100 scale. Higher scores on the symptom scales (e.g. Disease Symptoms, Side Effects of Treatment) represent higher levels of symptomatology or problems. High scores for Body Image and Future Perspective represent better quality of life or functioning.

    Measured: Baseline, EOT and follow-up (up to approximately 97 months)

  11. OS in High-Risk Participants

    Overall survival (OS) is defined as the time from the date of randomization to the date of death. High-risk participants are defined as participants carrying cytogenic abnormalities: del(17), translocation t(4;14), or t(14;16) as reported by the central laboratory combined with those cases that lacked a central laboratory result but with known del (17), t(4;14), or t(14;16) by local laboratory. Cytogenetic abnormalities of del(13) and +1q are not included in the analysis. Participants without documentation of death at the time of the analysis were censored at the date when they were last known to be alive. Data is only reported for high-risk participants.

    Measured: From the time of screening until disease progression and thereafter every 12 weeks until death or study termination (up to approximately 97 months)

  12. PFS in High-Risk Participants

    Progression Free Survival (PFS) is defined as the time from the date of randomization to the date of first documentation of disease progression or death due to any cause, whichever occurs first. Response was assessed by independent review committee (IRC) using IMWG response criteria. High-risk participants are defined as participants carrying cytogenic abnormalities: del(17), translocation t(4;14), or t(14;16) as reported by the central laboratory combined with those cases that lacked a central laboratory result but with known del (17), t(4;14), or t(14;16) by local laboratory. Cytogenetic abnormalities of del(13) and +1q are not included in the analysis.

    Measured: From date of randomization until disease progression or death up to approximately 38 months (approximate median follow-up 15 months)

  13. Plasma Concentration Over Time for Ixazomib

    Measured: Pre-dose and post-dose at multiple timepoints up to Cycle 10 Day 1 (each cycle length = 28 days)

  14. Overall Response Rate in Participants Defined by Polymorphism

    Data is reported for percentage of participants defined by polymorphism defined by polymorphisms in proteasome genes, such as polymorphism P11A in PSMB1 gene. Percentages are rounded off to single decimal.

    Measured: Day 1 of each cycle (every 4 weeks) until disease progression up to approximately 27 months (approximate median follow-up 15 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Mar 2012 (estimated)
  2. Study start1 Aug 2012
  3. Primary completion1 Oct 2014
  4. Study completion8 Feb 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
722 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01564537
Sponsor's protocol ID
C16010
Other IDs
2011-005496-17, CTR20130908, U1111-1164-7646, NL40132.018.12, 12/LO/0949, JapicCTI-132345, 1015042370, C16010CTIL
Status last verified
Feb 2023
First submitted
22 Mar 2012
Last updated
10 Mar 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Richardson PG, Kumar SK, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Gimsing P, Garderet L, Touzeau C, Buadi FK, Laubach JP, Cavo M, Darif M, Labotka R, Berg D, Moreau P. Final Overall Survival Analysis of the TOURMALINE-MM1 Phase III Trial of Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma. J Clin Oncol. 2021 Aug 1;39(22):2430-2442. doi: 10.1200/JCO.21.00972. Epub 2021 Jun 11.

    PubMed 34111952

  • Di Bacco A, Bahlis NJ, Munshi NC, Avet-Loiseau H, Masszi T, Viterbo L, Pour L, Ganly P, Cavo M, Langer C, Kumar SK, Rajkumar SV, Keats JJ, Berg D, Lin J, Li B, Badola S, Shen L, Zhang J, Esseltine DL, Luptakova K, van de Velde H, Richardson PG, Moreau P. c-MYC expression and maturity phenotypes are associated with outcome benefit from addition of ixazomib to lenalidomide-dexamethasone in myeloma. Eur J Haematol. 2020 Jul;105(1):35-46. doi: 10.1111/ejh.13405. Epub 2020 Apr 15.

    PubMed 32145111

  • Avet-Loiseau H, Bahlis NJ, Chng WJ, Masszi T, Viterbo L, Pour L, Ganly P, Palumbo A, Cavo M, Langer C, Pluta A, Nagler A, Kumar S, Ben-Yehuda D, Rajkumar SV, San-Miguel J, Berg D, Lin J, van de Velde H, Esseltine DL, di Bacco A, Moreau P, Richardson PG. Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. Blood. 2017 Dec 14;130(24):2610-2618. doi: 10.1182/blood-2017-06-791228. Epub 2017 Oct 20.

    PubMed 29054911

  • Gupta N, Yang H, Hanley MJ, Zhang S, Liu R, Kumar S, Richardson PG, Skacel T, Venkatakrishnan K. Dose and Schedule Selection of the Oral Proteasome Inhibitor Ixazomib in Relapsed/Refractory Multiple Myeloma: Clinical and Model-Based Analyses. Target Oncol. 2017 Oct;12(5):643-654. doi: 10.1007/s11523-017-0524-3.

    PubMed 28803351

  • Mateos MV, Masszi T, Grzasko N, Hansson M, Sandhu I, Pour L, Viterbo L, Jackson SR, Stoppa AM, Gimsing P, Hamadani M, Borsaru G, Berg D, Lin J, Di Bacco A, van de Velde H, Richardson PG, Moreau P. Impact of prior therapy on the efficacy and safety of oral ixazomib-lenalidomide-dexamethasone vs. placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1. Haematologica. 2017 Oct;102(10):1767-1775. doi: 10.3324/haematol.2017.170118. Epub 2017 Jul 27.

    PubMed 28751562

  • Hou J, Jin J, Xu Y, Wu D, Ke X, Zhou D, Lu J, Du X, Chen X, Li J, Liu J, Gupta N, Hanley MJ, Li H, Hua Z, Wang B, Zhang X, Wang H, van de Velde H, Richardson PG, Moreau P. Randomized, double-blind, placebo-controlled phase III study of ixazomib plus lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma: China Continuation study. J Hematol Oncol. 2017 Jul 6;10(1):137. doi: 10.1186/s13045-017-0501-4.

    PubMed 28683766

  • Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Simpson DR, Gimsing P, Palumbo A, Garderet L, Cavo M, Kumar S, Touzeau C, Buadi FK, Laubach JP, Berg DT, Lin J, Di Bacco A, Hui AM, van de Velde H, Richardson PG; TOURMALINE-MM1 Study Group. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Apr 28;374(17):1621-34. doi: 10.1056/NEJMoa1516282.

    PubMed 27119237

  • Moreau P, Hulin C, Macro M, Caillot D, Chaleteix C, Roussel M, Garderet L, Royer B, Brechignac S, Tiab M, Puyade M, Escoffre M, Stoppa AM, Facon T, Pegourie B, Chaoui D, Jaccard A, Slama B, Marit G, Laribi K, Godmer P, Luycx O, Eisenmann JC, Allangba O, Dib M, Araujo C, Fontan J, Belhadj K, Wetterwald M, Dorvaux V, Fermand JP, Rodon P, Kolb B, Glaisner S, Malfuson JV, Lenain P, Biron L, Planche L, Caillon H, Avet-Loiseau H, Dejoie T, Attal M. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood. 2016 May 26;127(21):2569-74. doi: 10.1182/blood-2016-01-693580. Epub 2016 Mar 21.

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Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ixazomib, Lenalidomide and Dexamethasone in people with Relapsed Multiple Myeloma and Refractory Multiple Myeloma, run by Takeda at 24 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) as Assessed by the Independent Review Committee (IRC) (time frame: From date of randomization until disease progression or death up to approximately 27 months (approximate median follow-up 15 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01564537, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2023.

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