A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)

Multiple Myeloma Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03173092
• Other study ID #: C16038
• Secondary ID: U1111-1192-7696
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: November 13, 2017
• Est. completion date: November 30, 2026

Study information

• Verified date: February 2024
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 141
• Est. completion date: November 30, 2026
• Est. primary completion date: November 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. 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.

3. Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0, 1, or 2 at time of enrollment.

4. 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).

5. 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:

1. 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.

2. Failure to have fully recovered (that is, less than or equal to [<=] Grade 1 toxicity) from the reversible effects of prior chemotherapy.

3. Major surgery within 14 days before enrollment.

4. 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).

5. Central nervous system involvement by MM.

6. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.

7. 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.

8. 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.

9. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus positive.

10. 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.

11. Has greater than or equal to (>=) Grade 2 peripheral neuropathy, or Grade 1 with pain on clinical examination during the screening period.

12. Have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not.

13. PD on first-line therapy.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Ixazomib
Ixazomib capsules.
• Lenalidomide
Lenalidomide capsules.
• Dexamethasone
Dexamethasone.

Locations

Country	Name	City	State
United States	Pacific Cancer Medical Center	Anaheim	California
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	Texas Oncology - Austin Midtown	Austin	Texas
United States	Saint Agnes Hospital	Baltimore	Maryland
United States	Regional Cancer Care Associates	Bethesda	Maryland
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	Karmanos Cancer Institute	Bloomfield Hills	Michigan
United States	Central Care Cancer Center	Bolivar	Missouri
United States	TriHealth Cancer Institute - Medical Oncology and Hematology Westside	Cincinnati	Ohio
United States	US Oncology Research	Colorado Springs	Colorado
United States	Texas Oncology - Presbyterian Cancer Center Dallas	Dallas	Texas
United States	Texas Oncology - El Paso Cancer Treatment Center Grandview	El Paso	Texas
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	Compassionate Care Research Group, Inc.	Fountain Valley	California
United States	American Health Network	Greenfield	Indiana
United States	Comprehensive Cancer Centers of Nevada	Henderson	Nevada
United States	Hematology Oncology Of Indiana	Indianapolis	Indiana
United States	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri
United States	CARTI Cancer Center	Little Rock	Arkansas
United States	Cancer Center Associates	Mesquite	Texas
United States	Veterans Affairs Tennessee Valley Healthcare System	Nashville	Tennessee
United States	Oschner Medical Center	New Orleans	Louisiana
United States	Illinois Cancer Specialists - Niles	Niles	Illinois
United States	Woodlands Medical Specialists - Pensacola	Pensacola	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	South Texas Veterans Health Care System	San Antonio	Texas
United States	Texas Oncology - San Antonio Northwest	San Antonio	Texas
United States	Millennium Physicians Association	Shenandoah	Texas
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Willamette Valley Cancer Institute and Research Center - Springfield	Springfield	Oregon
United States	Arizona Oncology Associates, P.C.	Tucson	Arizona
United States	Texas Oncology - Tyler	Tyler	Texas
United States	The Oncology Institute of Hope & Innovation	Whittier	California

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From date of first study drug administration until disease progression or death due to any cause, whichever occurs first (Up to 2 years).
Secondary	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.	Day 1 of each cycle (every 28 days) until disease progression for up to 3 years.
Secondary	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.	Day 1 of each cycle (every 28 days) until disease progression for up to 3 years.
Secondary	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.	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).
Secondary	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.	From the date of the first ixazomib administration to the date of the last ixazomib administration (Up to 3 years).
Secondary	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].	Up to 3 years
Secondary	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).	Up to 3 years.