Back to resultsA Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
Primary Purpose
Multiple Myeloma
Status
Active
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Ixazomib
Lenalidomide
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Drug therapy
Eligibility Criteria
Inclusion Criteria:
Must have a diagnosis of a MM using current IMWG diagnostic criteria and have received 1 prior line of therapy.
- Participants must have completed 3 cycles of a bortezomib-based induction regimen (as defined by current NCCN guidelines) and have no evidence of disease progression as defined by IMWG criteria.
- Participants with light chain and free light chain (FLC) only may be enrolled if they meet all the criteria for a diagnosis of MM.
- Participants must be considered by their physician eligible to receiving the IRD regimen.
Must be transplant ineligible as determined by their physician, or if transplant eligible, not expect to undergo transplant for at least 24 months after study enrollment.
o Stem cell harvest and mobilization regimen is acceptable if clinically indicated, but must first be confirmed by the Takeda Medical Monitor.
- Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2 at time of enrollment.
Female participants who:
- Are postmenopausal for at least 1 year before the screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the participant (periodic abstinence [example, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
Male participants, even if surgically sterilized (that is, status post-vasectomy), must agree to one of the following:
- Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence (example, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
Exclusion Criteria:
- Participation in other interventional clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial. Non-interventional trials (that is, observational trials) are permitted at any time point.
- Failure to have fully recovered (that is, less than or equal to [<=] Grade 1 toxicity) from the reversible effects of prior chemotherapy.
- Major surgery within 14 days before enrollment.
- Radiotherapy within 14 days before enrollment (if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib).
- Central nervous system involvement by MM.
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
- 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.
- Systemic treatment, within 14 days before the first dose of ixazomib, with strong cytochrome P450 3A (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.
- Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus positive.
- Diagnosed or treated for another malignancy within 2 years before study 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.
- Has greater than or equal to (>=) Grade 2 peripheral neuropathy, or Grade 1 with pain on clinical examination during the screening period.
- Have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not.
- PD on first-line therapy.
Sites / Locations
- Arizona Oncology Associates, P.C.
- CARTI Cancer Center
- Pacific Cancer Medical Center
- Compassionate Care Research Group, Inc.
- The Oncology Institute of Hope & Innovation
- US Oncology Research
- Woodlands Medical Specialists - Pensacola
- Grady Memorial Hospital
- Illinois Cancer Specialists - Niles
- American Health Network
- Hematology Oncology Of Indiana
- Oschner Medical Center
- Saint Agnes Hospital
- Regional Cancer Care Associates
- Karmanos Cancer Institute
- Central Care Cancer Center
- Kansas City Veterans Affairs Medical Center
- St. Vincent Frontier Cancer Center
- Comprehensive Cancer Centers of Nevada
- San Juan Oncology Associates
- TriHealth Cancer Institute - Medical Oncology and Hematology Westside
- Willamette Valley Cancer Institute and Research Center - Springfield
- Fox Chase Cancer Center
- Avera Cancer Institute
- Veterans Affairs Tennessee Valley Healthcare System
- Texas Oncology - Austin Midtown
- Texas Oncology - Presbyterian Cancer Center Dallas
- Texas Oncology - El Paso Cancer Treatment Center Grandview
- Cancer Center Associates
- South Texas Veterans Health Care System
- Texas Oncology - San Antonio Northwest
- Millennium Physicians Association
- Texas Oncology - Tyler
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg
Arm Description
Ixazomib 4 milligram (mg), capsules, orally, once, on Days 1, 8 and 15 and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21; and dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22 of a 28-day cycle for a maximum of 39 cycles until PD or unacceptable toxicity, whichever occurs first for up to 3 years.
Outcomes
Primary Outcome Measures
Progression Free Survival (PFS)
PFS is defined as time from date of first administration of study drug regimen to date of first documentation of progressive disease (PD) based on local laboratory results and investigator's assessment using modified International Myeloma Working Group (IMWG) response criteria or death due to any cause, whichever occurs first.
Secondary Outcome Measures
Percentage of Participants with Partial Response (PR), Very Good Partial Response (VGPR) and Complete Response (CR)
Response is based on investigator's assessment using modified IMWG criteria.
Duration of Response
Duration of response is defined as the time from the date of first documentation of a PR or better to the date of first documentation of PD for responders.
Duration of Treatment (DoT)
DoT is defined as the time from the date of the first administration of the study drug regimen (IRD) to the date of the last administration of any of the 3 study drugs in the regimen.
Duration of Ixazomib Therapy
Duration of ixazomib therapy is defined as the time from the date of the first administration of ixazomib therapy to the date of the last administration of ixazomib therapy.
Relative Dose Intensity (RDI) for Each Study Drug
RDI for each study drug is defined as 100*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals [dose prescribed at enrollment * number of prescribed doses per cycle * the number of treated cycles].
Duration of Proteasome Inhibitor Therapy
Duration of proteasome inhibitor therapy is defined as the time from the date of the first administration of bortezomib based therapy to the date of the last administration of the study drug (ixazomib).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03173092
Brief Title
A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
Official Title
An Open-Label, Single-Arm, Multicenter Study to Evaluate the Effectiveness and Safety of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) in Patients With Multiple Myeloma Previously Receiving a Bortezomib-Based Induction Regimen (US MM-6)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 20, 2017 (Actual)
Primary Completion Date
November 30, 2026 (Anticipated)
Study Completion Date
November 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The main aim is to evaluate the effect of Ixazomib in combination with lenalidomide and dexamethasone on Multiple Myeloma disease progression at 2 years in participants who previously received a bortezomib-based induction regimen.
The study will enroll approximately 160 participants, who are enrolled after completing 3 cycles of chemotherapy (Bortezomib-Based Induction Regimen). They are then treated with Ixazomib in addition to lenalidomide and dexamethasone.
Detailed Description
The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have MM. This study will look at the effectiveness and safety in participants who take the all-oral combination of ixazomib added to lenalidomide and dexamethasone.
The study will enroll approximately 160 participants. Participants will initially receive:
• Ixazomib 4 mg + lenalidomide 25 mg + dexamethasone 40 mg
Participants include MM participants who have received 3 cycles of a bortezomib-based induction regimen (as defined by current National Comprehensive Cancer Network [NCCN] guidelines) and have no evidence of PD following initial first-line therapy. All participants will be asked to take ixazomib 4 mg on Days 1, 8 and 15 and lenalidomide 25 mg from Day 1 through 21 and dexamethasone 40 mg on Days 1, 8, 15 and 22 in 28 day cycles until disease progression or unacceptable toxicity for up to 3 years.
Dose modifications of ixazomib, and/or lenalidomide and/or dexamethasone are allowed at the discretion of the physician.
This multi-center trial will be conducted in United States. It is anticipated that the treatment phase of this study will last up to 78 months, including 42 months for enrollment, and a 36-month IRD treatment period (39 cycles) with ixazomib and/or lenalidomide and/or dexamethasone for the last participant enrolled.
Participants will make multiple visits to the clinic as per their standard of care, and will be followed for PFS. After disease progression, participants will be followed-up for overall survival every 6 months until death or termination of the study by the sponsor.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Drug therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
141 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg
Arm Type
Experimental
Arm Description
Ixazomib 4 milligram (mg), capsules, orally, once, on Days 1, 8 and 15 and lenalidomide 25 mg, capsules, orally, once on Days 1 through 21; and dexamethasone 40 mg, tablets, orally, once on Days 1, 8, 15 and 22 of a 28-day cycle for a maximum of 39 cycles until PD or unacceptable toxicity, whichever occurs first for up to 3 years.
Intervention Type
Drug
Intervention Name(s)
Ixazomib
Other Intervention Name(s)
NINLARO, MLN9708
Intervention Description
Ixazomib capsules.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Lenalidomide capsules.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
PFS is defined as time from date of first administration of study drug regimen to date of first documentation of progressive disease (PD) based on local laboratory results and investigator's assessment using modified International Myeloma Working Group (IMWG) response criteria or death due to any cause, whichever occurs first.
Time Frame
From date of first study drug administration until disease progression or death due to any cause, whichever occurs first (Up to 2 years).
Secondary Outcome Measure Information:
Title
Percentage of Participants with Partial Response (PR), Very Good Partial Response (VGPR) and Complete Response (CR)
Description
Response is based on investigator's assessment using modified IMWG criteria.
Time Frame
Day 1 of each cycle (every 28 days) until disease progression for up to 3 years.
Title
Duration of Response
Description
Duration of response is defined as the time from the date of first documentation of a PR or better to the date of first documentation of PD for responders.
Time Frame
Day 1 of each cycle (every 28 days) until disease progression for up to 3 years.
Title
Duration of Treatment (DoT)
Description
DoT is defined as the time from the date of the first administration of the study drug regimen (IRD) to the date of the last administration of any of the 3 study drugs in the regimen.
Time Frame
From the date of the first study drug administration to the date of the last administration of any of the 3 study drugs (Up to 3 years).
Title
Duration of Ixazomib Therapy
Description
Duration of ixazomib therapy is defined as the time from the date of the first administration of ixazomib therapy to the date of the last administration of ixazomib therapy.
Time Frame
From the date of the first ixazomib administration to the date of the last ixazomib administration (Up to 3 years).
Title
Relative Dose Intensity (RDI) for Each Study Drug
Description
RDI for each study drug is defined as 100*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals [dose prescribed at enrollment * number of prescribed doses per cycle * the number of treated cycles].
Time Frame
Up to 3 years
Title
Duration of Proteasome Inhibitor Therapy
Description
Duration of proteasome inhibitor therapy is defined as the time from the date of the first administration of bortezomib based therapy to the date of the last administration of the study drug (ixazomib).
Time Frame
Up to 3 years.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Must have a diagnosis of a MM using current IMWG diagnostic criteria and have received 1 prior line of therapy.
Participants must have completed 3 cycles of a bortezomib-based induction regimen (as defined by current NCCN guidelines) and have no evidence of disease progression as defined by IMWG criteria.
Participants with light chain and free light chain (FLC) only may be enrolled if they meet all the criteria for a diagnosis of MM.
Participants must be considered by their physician eligible to receiving the IRD regimen.
Must be transplant ineligible as determined by their physician, or if transplant eligible, not expect to undergo transplant for at least 24 months after study enrollment.
o Stem cell harvest and mobilization regimen is acceptable if clinically indicated, but must first be confirmed by the Takeda Medical Monitor.
Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2 at time of enrollment.
Female participants who:
Are postmenopausal for at least 1 year before the screening visit, OR
Are surgically sterile, OR
If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, OR
Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the participant (periodic abstinence [example, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
Male participants, even if surgically sterilized (that is, status post-vasectomy), must agree to one of the following:
Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence (example, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).
Exclusion Criteria:
Participation in other interventional clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial. Non-interventional trials (that is, observational trials) are permitted at any time point.
Failure to have fully recovered (that is, less than or equal to [<=] Grade 1 toxicity) from the reversible effects of prior chemotherapy.
Major surgery within 14 days before enrollment.
Radiotherapy within 14 days before enrollment (if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib).
Central nervous system involvement by MM.
Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
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.
Systemic treatment, within 14 days before the first dose of ixazomib, with strong cytochrome P450 3A (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.
Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus positive.
Diagnosed or treated for another malignancy within 2 years before study 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.
Has greater than or equal to (>=) Grade 2 peripheral neuropathy, or Grade 1 with pain on clinical examination during the screening period.
Have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not.
PD on first-line therapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Oncology Associates, P.C.
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85704
Country
United States
Facility Name
CARTI Cancer Center
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Pacific Cancer Medical Center
City
Anaheim
State/Province
California
ZIP/Postal Code
92801
Country
United States
Facility Name
Compassionate Care Research Group, Inc.
City
Fountain Valley
State/Province
California
ZIP/Postal Code
92708
Country
United States
Facility Name
The Oncology Institute of Hope & Innovation
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
US Oncology Research
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Woodlands Medical Specialists - Pensacola
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32503
Country
United States
Facility Name
Grady Memorial Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Illinois Cancer Specialists - Niles
City
Niles
State/Province
Illinois
ZIP/Postal Code
60714
Country
United States
Facility Name
American Health Network
City
Greenfield
State/Province
Indiana
ZIP/Postal Code
46140
Country
United States
Facility Name
Hematology Oncology Of Indiana
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Oschner Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Saint Agnes Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21229
Country
United States
Facility Name
Regional Cancer Care Associates
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Karmanos Cancer Institute
City
Bloomfield Hills
State/Province
Michigan
ZIP/Postal Code
48302
Country
United States
Facility Name
Central Care Cancer Center
City
Bolivar
State/Province
Missouri
ZIP/Postal Code
65613
Country
United States
Facility Name
Kansas City Veterans Affairs Medical Center
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64128
Country
United States
Facility Name
St. Vincent Frontier Cancer Center
City
Billings
State/Province
Montana
ZIP/Postal Code
59102
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89052
Country
United States
Facility Name
San Juan Oncology Associates
City
Farmington
State/Province
New Mexico
ZIP/Postal Code
87401
Country
United States
Facility Name
TriHealth Cancer Institute - Medical Oncology and Hematology Westside
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45247
Country
United States
Facility Name
Willamette Valley Cancer Institute and Research Center - Springfield
City
Springfield
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Avera Cancer Institute
City
Sioux Falls
State/Province
South Dakota
ZIP/Postal Code
57105
Country
United States
Facility Name
Veterans Affairs Tennessee Valley Healthcare System
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
Texas Oncology - Austin Midtown
City
Austin
State/Province
Texas
ZIP/Postal Code
78705
Country
United States
Facility Name
Texas Oncology - Presbyterian Cancer Center Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Texas Oncology - El Paso Cancer Treatment Center Grandview
City
El Paso
State/Province
Texas
ZIP/Postal Code
79902
Country
United States
Facility Name
Cancer Center Associates
City
Mesquite
State/Province
Texas
ZIP/Postal Code
75150
Country
United States
Facility Name
South Texas Veterans Health Care System
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Texas Oncology - San Antonio Northwest
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78240
Country
United States
Facility Name
Millennium Physicians Association
City
Shenandoah
State/Province
Texas
ZIP/Postal Code
77385
Country
United States
Facility Name
Texas Oncology - Tyler
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Learn more about this trial
A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
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