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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)

NCT03173092

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 4

Trial Eligibility

Document

Title

  • Brief Title: 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)
  • 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 IDs

  • ORG STUDY ID: C16038
  • SECONDARY ID: U1111-1192-7696
  • NCT ID: NCT03173092

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
IxazomibNINLARO, MLN9708Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg
LenalidomideIxazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg
DexamethasoneIxazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mg

Purpose

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.

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 2 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 36 months, including 12 months for enrollment,
      and a 24-month IRD treatment period (26 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.
    

Trial Arms

NameTypeDescriptionInterventions
Ixazomib 4 mg + Lenalidomide 25 mg + Dexamethasone 40 mgExperimentalIxazomib 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 26 cycles until PD or unacceptable toxicity, whichever occurs for up to 2 years.
  • Ixazomib
  • Lenalidomide
  • Dexamethasone

Eligibility Criteria

        Inclusion Criteria:

          1. Must have a diagnosis of a MM using current International Myeloma Working Group (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.

             • 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.

        Exclusion Criteria:

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

          2. Major surgery within 14 days before enrollment.

          3. 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.)

          4. Central nervous system involvement.

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

          6. 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.

          7. 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.

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

          9. 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 non-melanoma skin cancer or carcinoma in situ of any type
             are not excluded if they have undergone complete resection.

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

         11. PD on first-line therapy.

         12. 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
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)
Safety Issue:
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.

Secondary Outcome Measures

Measure:Percentage of Participants with Partial Response (PR), Very Good Partial Response (VGPR) and Complete Response (CR)
Time Frame:Day 1 of each cycle (every 28 days) until disease progression for up to 2 years
Safety Issue:
Description:Response is based on investigator's assessment using modified IMWG criteria.
Measure:Duration of Response
Time Frame:Day 1 of each cycle (every 28 days) until disease progression for up to 2 years
Safety Issue:
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.
Measure:Duration of Therapy (DoT)
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 2 years)
Safety Issue:
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.
Measure:Duration of Ixazomib Therapy
Time Frame:From the date of the first ixazomib administration to the date of the last ixazomib administration (Up to 2 years)
Safety Issue:
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.
Measure:Relative Dose Intensity (RDI) for Each Study Drug
Time Frame:Up to 2 years
Safety Issue:
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].

Details

Phase:Phase 4
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Millennium Pharmaceuticals, Inc.

Trial Keywords

  • Drug therapy

Last Updated

August 12, 2019