An Effectiveness and Safety Study of Ixazomib in Combination With Lenalidomide and Dexamethasone (IRD) in Participants With Multiple Myeloma (MM) Previously Receiving a Bortezomib-based Induction Regimen (US MM-6)

Sponsor

Millennium Pharmaceuticals, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03173092

Collaborator

(none)

141

Enrollment

Locations

Arm

110.3

Anticipated Duration (Months)

4.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the progression-free survival (PFS) at 2 years for MM participants previously receiving a bortezomib-based induction regimen to IRD.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Ixazomib Drug: Lenalidomide Drug: Dexamethasone	Phase 4

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 ixazomib in addition 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

141 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Sep 20, 2017

Anticipated Primary Completion Date :

Nov 30, 2026

Anticipated Study Completion Date :

Nov 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg 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 for up to 3 years.	Drug: Ixazomib Ixazomib capsules. Other Names: NINLARO MLN9708 Drug: Lenalidomide Lenalidomide capsules. Drug: Dexamethasone Dexamethasone.

Arm

Intervention/Treatment

Experimental: Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg

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 for up to 3 years.

Drug: Ixazomib

Ixazomib capsules.

Other Names:

NINLARO

MLN9708

Drug: Lenalidomide

Lenalidomide capsules.

Drug: Dexamethasone

Dexamethasone.

Outcome Measures

Primary Outcome Measures

Progression Free Survival (PFS) [From date of first study drug administration until disease progression or death due to any cause, whichever occurs first (Up to 2 years)]
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) [Day 1 of each cycle (every 28 days) until disease progression for up to 2 years]
Response is based on investigator's assessment using modified IMWG criteria.
Duration of Response [Day 1 of each cycle (every 28 days) until disease progression for up to 2 years]
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 Therapy (DoT) [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)]
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 [From the date of the first ixazomib administration to the date of the last ixazomib administration (Up to 3 years)]
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 [Up to 3 years]
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].

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates, P.C.	Tucson	Arizona	United States	85704
2	CARTI Cancer Center	Little Rock	Arkansas	United States	72205
3	Pacific Cancer Medical Center	Anaheim	California	United States	92801
4	Compassionate Care Research Group, Inc.	Fountain Valley	California	United States	92708
5	The Oncology Institute of Hope & Innovation	Whittier	California	United States	90603
6	US Oncology Research	Colorado Springs	Colorado	United States	80218
7	Woodlands Medical Specialists - Pensacola	Pensacola	Florida	United States	32503
8	Grady Memorial Hospital	Atlanta	Georgia	United States	30303
9	Illinois Cancer Specialists - Niles	Niles	Illinois	United States	60714
10	American Health Network	Greenfield	Indiana	United States	46140
11	Hematology Oncology Of Indiana	Indianapolis	Indiana	United States	46260
12	Oschner Medical Center	New Orleans	Louisiana	United States	70121
13	Saint Agnes Hospital	Baltimore	Maryland	United States	21229
14	Regional Cancer Care Associates	Bethesda	Maryland	United States	20817
15	Karmanos Cancer Institute	Bloomfield Hills	Michigan	United States	48302
16	Central Care Cancer Center	Bolivar	Missouri	United States	65613
17	Kansas City Veterans Affairs Medical Center	Kansas City	Missouri	United States	64128
18	St. Vincent Frontier Cancer Center	Billings	Montana	United States	59102
19	Comprehensive Cancer Centers of Nevada	Henderson	Nevada	United States	89052
20	San Juan Oncology Associates	Farmington	New Mexico	United States	87401
21	TriHealth Cancer Institute - Medical Oncology and Hematology Westside	Cincinnati	Ohio	United States	45247
22	Willamette Valley Cancer Institute and Research Center - Springfield	Springfield	Oregon	United States	97401
23	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
24	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
25	Veterans Affairs Tennessee Valley Healthcare System	Nashville	Tennessee	United States	37212
26	Texas Oncology - Austin Midtown	Austin	Texas	United States	78705
27	Texas Oncology - Presbyterian Cancer Center Dallas	Dallas	Texas	United States	75231
28	Texas Oncology - El Paso Cancer Treatment Center Grandview	El Paso	Texas	United States	79902
29	Cancer Center Associates	Mesquite	Texas	United States	75150
30	South Texas Veterans Health Care System	San Antonio	Texas	United States	78229
31	Texas Oncology - San Antonio Northwest	San Antonio	Texas	United States	78240
32	Millennium Physicians Association	Shenandoah	Texas	United States	77385
33	Texas Oncology - Tyler	Tyler	Texas	United States	75702