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Relapsed and/or Refractory Multiple MyelomaPhase 2NCT02917941

A Study of Ixazomib Plus Lenalidomide and Dexamethasone in Adult Japanese Participants With Relapsed and/or Refractory Multiple Myeloma

A Phase 2 study testing Ixazomib, Lenalidomide and Dexamethasone in people with Relapsed and/or Refractory Multiple Myeloma, run by Takeda at 21 sites in Japan.

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 evaluate the efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese participants with relapsed and/or refractory multiple myeloma (RRMM). Read more about this study

Who is it for?
Ages 20 years and older
What is being tested?
Ixazomib, Lenalidomide and Dexamethasone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
21 sitesJapan
Study dates
1 Nov 2016to 31 Aug 2019
Phase
Phase 2
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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female Japanese participants 20 years of age or older.
  • Multiple myeloma (MM) diagnosed according to standard criteria either currently or at the time of initial diagnosis.
  • The initial diagnosis must be symptomatic MM, although the relapsed disease does not need to be symptomatic.
  • Participants must have measurable disease defined by at least 1 of the following 3 measurements based on central laboratory data:
  • Serum M-protein: >=1 g/dL (>= 10 g/L).
  • Urine M-protein: >=200 mg/24 hours.
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  • Serum free light chain assay: involved free light chain level >=10 mg/dL (>= 100 mg/L), provided that the serum free light chain ratio is abnormal.
  • Participants with RRMM who have received 1 to 3 prior therapies.
  • This participant population includes the following 3 categories of participants:
  • Participants who relapsed from their therapy(s) but were not refractory to any previous therapy.
  • Participants who were refractory to all lines of previous therapy(s) (ie, participants who have never responded to any therapies received).
  • Participants who were relapsed from at least 1 line of therapy AND additionally were refractory to at least 1 line of therapy. For the purposes of this study, refractory MM is defined as PD on therapy or PD within 60 days after the last dose of a given therapy.
  • A line of therapy is defined as 1 or more cycles of a planned treatment program. This may consist 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 is considered 1 line of therapy. Autologous and allogenic transplants are permitted.
  • Participants must meet the following clinical laboratory criteria:
  • Absolute neutrophil count (ANC) >= 1,000/mm3, hemoglobin >= 8 g/dL and platelet count >= 75,000/mm3. Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days prior to screening.
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Participants who received prior allogenic transplant must have no active graft-versus-host disease (GVHD).
  • Participants who meet the following conditions:
  • Female participants who:
  • Are postmenopausal for at least 24 months before the screening visit, OR
  • Are surgically sterile, OR
  • Females of childbearing potential must:
  • Have 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
  • Agree to practice true abstinence or to begin TWO reliable methods of birth control (1 highly effective method and 1 additional effective method AT THE SAME TIME) for at least 28 days before starting the study treatment through 90 days after the last dose of the study treatment.
  • Agree to ongoing pregnancy testing
  • Adhere to the guidelines of the RevMate program
  • Male participants, even if surgically sterilized (ie, status postvasectomy), must:
  • Agree to avoid sexual intercourse completely 90 days after the last dose of the study treatment.
  • Agree to practice true abstinence or to practice effective barrier contraception during the entire study treatment period and 90 days after the last dose of the study treatment if their partner is of childbearing potential, even if they have had a successful vasectomy, and
  • Adhere to the guidelines of the RevMate program
  • Thromboembolism prophylaxis is required based on published standard or institutional standard of care.
  • Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
  • Participant is willing and able to adhere to the study visit schedule and other protocol requirements.

Who cannot join

  • Participants who were refractory to lenalidomide or proteasome inhibitor-based therapy at any line.
  • Refractory disease is defined as PD on treatment or PD within 60 days after the last dose of a given therapy. Participants who progressed the disease after 60 days from the last dose of a given therapy will be considered relapsed and are eligible for inclusion in the study.
  • Participants who were refractory to thalidomide-based therapy are eligible.
  • Female participants who are breast feeding or pregnant.
  • Failure to have fully recovered (ie, =< Grade 1 toxicity) from the effects of prior chemotherapy (except for hair loss) regardless of the interval since the last treatment.
  • Major surgery within 14 days before enrollment.
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  • Radiotherapy within 14 days before enrollment.
  • Central nervous system involvement.
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment.
  • Rash or pruritus requiring systemic medication within 14 days before enrollment.
  • 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 the past 6 months before enrollment.
  • Systemic treatment with strong cytochrome P450, family 3, subfamily A (CYP3A) inducers (rifampicin, carbamazepine, phenytoin), or St. John's wort within 14 days before enrollment.
  • Ongoing or active systemic infection, known human immunodeficiency virus (HIV)- positive, known hepatitis B surface antigen seropositive or known hepatitis C virus (HCV)-RNA positive.
  • Participants who have positive hepatitis B core antibody (HBcAb) can be enrolled but must have hepatitis B virus (HBV)-DNA negative. Participants who have positive hepatitis C antibody can be enrolled but must have HCV-RNA negative.
  • 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 enrollment 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.
  • Participants who have participated in a clinical trial of ixazomib, or have been treated with ixazomib.

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

Japan21 sites

  • Study site

    Bunkyo-ku, Tokyo

  • Study site

    Chiba

  • Study site

    Fukuoka

  • Study site

    Fukuyama, Hiroshima

  • Study site

    Ibaraki, Ibaragi

  • Study site

    Ikoma, Nara

  • Study site

    Kobe, Hyōgo

  • Study site

    Koto-ku, Tokyo

  • Study site

    Nagoya, Aichi-ken

  • Study site

    Narita, Chiba

  • Study site

    Niigata

  • Study site

    Okayama

  • Study site

    Osaka

  • Study site

    Sagamihara, Kanagawa

  • Study site

    Sendai, Miyagi

  • Study site

    Shibukawa, Gunma

  • Study site

    Shibuya-ku, Tokyo

  • Study site

    Shinjuku-ku, Tokyo

  • Study site

    Sunto-gun, Shizuoka

  • Study site

    Tachikawa, Tokyo

  • Study site

    Utsunomiya, Tochigi

Other trials in Japan

About this study

Official title: A Phase 2, Open-Label, Multicenter Study of Ixazomib Plus Lenalidomide and Dexamethasone in Adult Japanese Patients With Relapsed and/or Refractory Multiple Myeloma

The purpose of this study is to evaluate the efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese participants with relapsed and/or refractory multiple myeloma (RRMM).

Read the detailed description

This is a phase 2, open label, single arm, multicenter study to evaluate the efficacy and safety of ixazomib plus lenalidomide and dexamethasone in Japanese participants with relapsed and/or refractory multiple myeloma (MM). The participants population will consist of adult men and women who have a confirmed diagnosis of MM, who have received 1 to 3 prior lines of therapy, and who meet other outlined eligibility criteria. Participants will receive study drug (ixazomib 4.mg) on Days 1, 8, and 15 plus lenalidomide (25 mg) on Days 1 through 21 and dexamethasone (40 mg) on Days 1, 8, 15, and 22 of a 28-day cycle. Participants may continue to receive treatment until progressive disease (PD) or unacceptable toxicity, whichever comes first. Dose modifications may be made based on toxicities. Participant with a low creatinine clearance < 60 mL/min will receive a reduced lenalidomide dose of 10 mg once daily on Days 1 through 21 of a 28-day cycle. The lenalidomide dose may be escalated to 15 mg once daily after 2 cycles if the participant is not responding to treatment and is tolerating the treatment. If renal function normalizes (ie, creatinine clearance >= 60 mL/min) and the participant continues to tolerate this treatment, lenalidomide may then be escalated to 25 mg once daily.

Treatment periods will be defined as 28-day cycles. Participant will be seen at regular treatment cycle intervals while they are participating in the study: four times a treatment cycle for the first 2 cycles, twice a treatment cycle for the 3rd cycle, and then once a treatment cycle for the remainder of their participation in the active treatment and, if applicable, the progression free survival (PFS) and overall survival (OS) follow-up phases of the study.

Response will be assessed by investigator according to the International Myeloma Working Group criteria for all participants every 4 weeks until PD. Central laboratory data will be used for serum M-protein, urine M-protein and serum free light chain. All participants will be followed for survival after progression. Participants will be contacted every 12 weeks until death or termination of the study by the sponsor.

The study will be closed at 24 months from the enrollment of the last participant.

Being tested
Ixazomib, Lenalidomide, Dexamethasone

What participants receive

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

Study groups in NCT02917941
Study groupRoleWhat they receive
Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mgExperimentalIxazomib 4 mg, capsules, orally on Days 1, 8, and 15 plus lenalidomide 25 mg, capsule, orally, once daily on Days 1 through 21 and dexamethasone 40 mg, tablet, orally on Days 1, 8, 15, and 22 of a 28-day cycle up to 32 cycles.
Receives: Drug: Ixazomib; Drug: Lenalidomide; Drug: Dexamethasone

What is being measured

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

  1. Percentage of Participants With Very Good Partial Response (VGPR) or Better Response (Complete Response (CR) + VGPR)

    Response was assessed using International Myeloma Working Group (IMWG) Criteria. CR was defined as negative immunofixation in serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR was 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.

    Measured: Up to approximately 33 months

Secondary outcomes (8)

  1. Progression-free Survival (PFS)

    PFS was defined as the time in months from the date of first study drug administration to the date of first documentation of PD or death from any cause, whichever occurred first. PD required one 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 participants 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.

    Measured: Up to approximately 33 months

  2. Overall Response Rate (ORR)

    ORR:percentage of participants with CR including stringent complete response(sCR),VGPR,partial response(PR) per independent review committee(IRC)by IMWG criteria.CR: serum,urine -ve immunofixation; disappearance of soft tissue plasmacytomas,<5%plasma cells in bone marrow(CR in those with only measurable disease by serum FLC levels=normal FLC ratio 0.26 to 1.65+CR criteria).sCR:CR+normal FLC ratio,absence of clonal plasma cells(immunohistochemistry)or 2-to 4-color flow cytometry.VGPR:serum,urine M-protein detectable by immunofixation,not by electrophoresis or ≥90%reduction,<100mg/24hrs(VGPR in those with only measurable disease by serum FLC levels,requires>90%decrease in involved-uninvolved FLC level difference).PR: ≥50%reduction of serum M protein+reduction in 24-hr urinary M protein by≥90%/ to<200mg/24-hr or ≥50%decrease in difference between involved-uninvolved FLC levels/≥50%reduction in bone marrow plasma cells,if≥30%at baseline/≥50%soft tissue plasmacytoma size reduction.

    Measured: Up to approximately 33 months

  3. Duration of Response (DOR)

    DOR was measured as time in months from date of first documentation of response, VGPR or better, and ORR (CR+PR (including sCR and VGPR) or better, to date of first documented PD among participants who responded to treatment. Response was assessed by investigator using IMWG Criteria. CR:negative immunofixation in serum and urine and; disappearance of any soft tissue plasmacytomas and;<5% plasma cells in bone marrow. sCR:CR plus normal FLC ratio, absence of clonal plasma cells by immunohistochemistry or 2- to 4-color flow cytometry. VGPR:serum and urine M-protein detectable by immunofixation but not on electrophoresis/≥90% reduction in serum M-protein plus urine M-protein level <100 mg/24 hours. PR:≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to <200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved FLC levels/≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/≥50% reduction in size of soft tissue plasmacytomas.

    Measured: Up to approximately 33 months

  4. Time to Progression (TTP)

    TTP was measured as the time in months from the first dose of study treatment to the date of the first documented PD as assessed using IMWG criteria. PD required one 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 participants without measurable serum and urine M-protein levels the difference between involved and uninvolved 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.

    Measured: Up to approximately 33 months

  5. Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs)

    An adverse event (AE) is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it was related to the medicinal product. A TEAE is defined as any AE that occurred after administration of the first dose of any study drug through 30 days after the last dose of any study drug.

    Measured: Up to approximately 33 months

  6. Number of Participants With NCI CTCAE Grade 3 or Higher TEAEs Related Laboratory Parameters

    Laboratory parameters included chemistry and hematology. An AE is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it was related to the medicinal product. A TEAE is defined as any AE that occurred after administration of the first dose of any study drug through 30 days after the last dose of any study drug. An AE was graded as per NCI CTCAE.

    Measured: Up to approximately 33 months

  7. Number of Participants With NCI CTCAE Grade 3 or Higher TEAEs Related to Vital Signs

    Vital signs included temperature, blood pressure, heart rate, and respiratory rate. An AE is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it was related to the medicinal product. A TEAE is defined as any AE that occurred after administration of the first dose of any study drug through 30 days after the last dose of any study drug. An AE was graded as per NCI CTCAE.

    Measured: Up to approximately 33 months

  8. Overall Survival (OS)

    OS was defined as the time from the date of first study drug administration to the date of death.

    Measured: Up to approximately 33 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 Sep 2016 (estimated)
  2. Study start1 Nov 2016
  3. Primary completion31 Aug 2019
  4. Study completion31 Aug 2019

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02917941
Sponsor's protocol ID
C16028
Other IDs
U1111-1187-4027, JapicCTI-163381
Status last verified
Dec 2020
First submitted
22 Sep 2016
Last updated
12 Jan 2021
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • Iida S, Izumi T, Komeno T, Terui Y, Chou T, Ikeda T, Berg D, Fukunaga S, Sugiura K, Sasaki M. A phase 2, open-label, multicenter study of ixazomib plus lenalidomide and dexamethasone in adult Japanese patients with relapsed and/or refractory multiple myeloma. Int J Clin Oncol. 2022 Jan;27(1):224-233. doi: 10.1007/s10147-021-02030-7. Epub 2021 Oct 2.

    PubMed 34599726

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ixazomib, Lenalidomide and Dexamethasone in people with Relapsed and/or Refractory Multiple Myeloma, run by Takeda at 21 sites in Japan.

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 36 inclusion and 21 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 12 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Japan. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 18 Sep 2020). 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?

Percentage of Participants With Very Good Partial Response (VGPR) or Better Response (Complete Response (CR) + VGPR) (time frame: Up to approximately 33 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 NCT02917941, which also lists 1 linked publication.

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 12 Jan 2021.

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