Trial record 1 of 1 for:    NCT02046070
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Phase 2 Study to Evaluate the Oral Combination of Ixazomib (MLN9708) With Cyclophosphamide and Dexamethasone in Patients With Newly Diagnosed or Relapsed and/or Refractory Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Millennium Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02046070
First received: December 12, 2013
Last updated: October 21, 2014
Last verified: October 2014
  Purpose

This is a phase 2, multicenter, open-label study in patients with Newly Diagnosed Multiple Myeloma (NDMM) who have not received prior systemic treatment for multiple myeloma (MM) and who are ineligible for high-dose therapy (HDT)-stem cell transplantation (SCT) due to age (ie, ≥ 65 years) or comorbid disease(s) or with Relapsed and/or Refractory Multiple Myeloma (RRMM)).


Condition Intervention Phase
Multiple Myeloma
Drug: Cyclophosphamide
Drug: Ixazomib (MLN9708)
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 2 Study to Evaluate the Oral Combination of Ixazomib (MLN9708) With Cyclophosphamide and Dexamethasone in Patients With Newly Diagnosed or Relapsed and/or Refractory Multiple Myeloma Requiring Systemic Treatment

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Combined Response Rate during the Induction Phase in Newly Diagnosed Multiple Myeloma (NDMM) Participants [ Time Frame: Day 1 of Cycles 1-13, 28-day cycles (Up to 1 year) ] [ Designated as safety issue: No ]
    Combined Response Rate is the percentage of participants with Complete Response (CR), including stringent Complete Response (sCR), and Very Good Partial Response (VGPR) according to the International Myeloma Working Group (IMWG) criteria during the induction phase (Cycles 1-13, 28-day cycles).

  • Overall Response Rate (ORR) in Relapsed and/or Refractory Multiple Myeloma (RRMM) Participants [ Time Frame: Day 1 of each 28 day cycle (Up to 36 months) ] [ Designated as safety issue: No ]
    ORR is the percentage of participants with Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) according to IMWG criteria.


Secondary Outcome Measures:
  • Number of Participants with Adverse Events (AEs), Grade 3 or higher AEs, AEs resulting in discontinuation, AEs resulting in dose reduction and Serious Adverse Events (SAEs) in NDMM Participants [ Time Frame: First dose of study drug through 30 days after last dose of drug (Up to 36 months) ] [ Designated as safety issue: Yes ]

    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.

    Serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug will be determined by the Investigator.


  • Overall response rate (ORR), CR, VGPR, PR and stable disease (SD), progressive disease(PD) during the Induction Phase and the ORR (CR + VGPR + PR), CR + VGPR, CR, VGPR, and PR through out the entire treatment period in NDMM Participants [ Time Frame: Day 1 of Cycles 1-13, 28-day cycles (Up to 1 year) ] [ Designated as safety issue: No ]
    Percentage of participants with ORR [defined as Complete Response (CR) + Very Good Partial Response (VGPR) + Partial Response (PR)], CR, VGPR and PR according to IMWG criteria in the induction Phase (Cycles 1-13, 28-day cycles).

  • Time to Response (TTR) in NDMM Participants [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
    TTR is defined as the time interval from the date of enrollment to the date of the first documented response during the induction phase.

  • Duration of Response (DOR) in NDMM Participants [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    DOR is defined as the time interval from the date of first response to the date of disease progression.

  • Time to Progression (TTP) in NDMM Participants [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    TTP is defined as the time interval from the date of enrollment to the date of first documented disease progression.

  • Progression Free Survival (PFS) in NDMM Participants [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    PFS is defined as the time interval from the date of enrollment to the date of the first documented disease progression or death.

  • Number of participants with AEs, SAEs, AEs resulting in discontinuation and AEs resulting in dose reduction in NDMM Participants Remaining on Treatment after 13 Cycles [ Time Frame: Enrollment through 30 days after the last dose of drug (Up to 36 months) ] [ Designated as safety issue: No ]

    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug.

    Serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug will be determined by the Investigator.


  • Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) during the Induction Phase in NDMM Participants [ Time Frame: Baseline (Day 1-Cycle 1), Day 1 of each 28-day cycles 2-13 (Up to 1 year) ] [ Designated as safety issue: No ]
    The EOTRC QLQ-C30 is a patient completed 30 item questionnaire that consists of 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The patient evaluates their health status over the previous week. There are 28 questions answered on a 4-point scale where1=Not at all (best) to 4=Very Much (worst) and 2 questions answered on a 7-point scale where 1=Very poor (worst) to 7= Excellent (best) for a total possible score of 0 to 100, where higher scores indicate better Global Health Status. Negative changes from Baseline indicate deterioration in quality of life or functioning and positive changes indicate improvement.

  • ORR, CR, VGPR, and PR in NDMM Participants Remaining on Treatment after 13 Cycles [ Time Frame: Day 1 of each 28-day Cycle (Up to 36 months) ] [ Designated as safety issue: No ]
    Percentage of participants with Overall Response (CR + VGPR + PR) , Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR) according to IMWG criteria.

  • Cmax: Maximum Observed Plasma Concentration in NDMM Participants [ Time Frame: Days 1-3, 5, 8, 15-17, 19 and 22 during cycle 1 and day 1 of cycle 2 (safety lead-in patients) or days 1, 8, 15, and 22 during cycles 1-3 (excluding safety lead-in) ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. PK analysis is based on concentrations of MLN2238, the complete hydrolysis product of ixazomib.

  • Tmax: Time to reach the maximum plasma concentration (Cmax) in NDMM Participants [ Time Frame: Days 1-3, 5, 8, 15-17, 19 and 22 during cycle 1 and day 1 of cycle 2 (safety lead-in patients) or days 1, 8, 15, and 22 during cycles 1-3 (excluding safety lead-in) ] [ Designated as safety issue: No ]
    Tmax is the time in hours to reach the maximum plasma concentration. PK analysis is based on concentrations of MLN2238, the complete hydrolysis product of ixazomib.

  • AUC: Area under the Plasma Concentration Versus Time Curve in NDMM Participants [ Time Frame: Days 1-3, 5, 8, 15-17, 19 and 22 during cycle 1 and day 1 of cycle 2 (safety lead-in patients) or days 1, 8, 15, and 22 during cycles 1-3 (excluding safety lead-in) ] [ Designated as safety issue: No ]
    PK analysis for AUC is based on concentrations of ixazomib (MLN9708).

  • Number of Participants with Adverse Events (AEs), Grade 3 or higher AEs, AEs resulting in discontinuation, AEs resulting in dose reduction, serious adverse events (SAEs) in RRMM Participants [ Time Frame: First dose of study drug through 30 days after last dose of drug (Up to 36 months) ] [ Designated as safety issue: No ]

    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment.

    Serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. Relationship of each AE to study drug will be determined by the Investigator.


  • Cmax: Maximum Observed Plasma Concentration in RRMM Participants [ Time Frame: Days 1-3, 5, 8, 15-17, 19 and 22 during cycle 1 and day 1 of cycle 2 (safety lead-in patients) or days 1, 8, 15, and 22 during cycles 1-3 (excluding safety lead-in) ] [ Designated as safety issue: No ]
    Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. PK analysis is based on concentrations of MLN2238, the complete hydrolysis product of ixazomib (MLN9708).

  • Tmax: Time to reach the maximum plasma concentration (Cmax) in RRMM Participants [ Time Frame: Days 1-3, 5, 8, 15-17, 19 and 22 during cycle 1 and day 1 of cycle 2 (safety lead-in patients) or days 1, 8, 15, and 22 during cycles 1-3 (excluding safety lead-in) ] [ Designated as safety issue: No ]
    Tmax is the time in hours to reach maximum plasma concentration. PK analysis is based on concentrations of MLN2238, the complete hydrolysis product of ixazomib.

  • AUC: Area under the Plasma Concentration Versus Time Curve in RRMM Participants [ Time Frame: Days 1-3, 5, 8, 15-17, 19 and 22 during cycle 1 and day 1 of cycle 2 (safety lead-in patients) or days 1, 8, 15, and 22 during cycles 1-3 (excluding safety lead-in) ] [ Designated as safety issue: No ]
    PK analysis of AUC is based on concentrations of MLN2238, the complete hydrolysis product of ixazomib.

  • CR + VGPR , CR, VGPR, PR, SD and PD in RRMM Participants [ Time Frame: Day 1 of each 28-day Cycle (Up to 36 months) ] [ Designated as safety issue: No ]
    Percentage of participants with Complete Response (CR) + Very Good Partial Response (VGPR), CR, VGPR, Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD) according to IMWG criteria throughout the study.

  • Time to Response (TTR) in RRMM Participants [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    TTR is defined as the time interval from the date of enrollment to the date of the first documented response during the induction phase.

  • Duration of Response (DOR) in RRMM Participants [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    DOR is defined as the time interval from the date of first response to the date of disease progression.

  • Time to Progression (TTP) in RRMM Participants [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    TTP is defined as the time interval from the date of enrollment to the date of first documented disease progression.

  • Progression Free Survival (PFS) in RRMM Participants [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    PFS is defined as the time interval from the date of enrollment to the date of the first documented disease progression or death.

  • Change from Baseline in EORTC Quality of Life Questionnaire (QLQ-C30) in RRMM Participants [ Time Frame: Baseline (Day 1-Cycle 1), Day 1 of each 28-day cycle (Up to 36 months) ] [ Designated as safety issue: No ]
    The EOTRC QLQ-C30 is a patient completed 30 item questionnaire that consists of 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The patient evaluates their health status over the previous week. There are 28 questions answered on a 4-point scale where1=Not at all (best) to 4=Very Much (worst) and 2 questions answered on a 7-point scale where 1=Very poor (worst) to 7= Excellent (best) for a total possible score of 0 to 100, where higher scores indicate better Global Health Status. Negative changes from Baseline indicate deterioration in quality of life or functioning and positive changes indicate improvement.


Estimated Enrollment: 148
Study Start Date: March 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ixazomib (MLN9708) + 300mg/m^2 Cyclophosphamide_ NDMM
Ixazomib (MLN9708) 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity [13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months] and cyclophosphamide 300 mg/m^2, tablets, orally, Days 1, 8 and 15 of a 28-day cycle for 13 cycles or PD/death or unacceptable toxicity and dexamethasone 40 mg, tablets, orally, Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients >75 years) of a 28-day cycle for 13 cycles or PD/death or unacceptable toxicity in participants with NDMM.
Drug: Cyclophosphamide
Cyclophosphamide tablets
Drug: Ixazomib (MLN9708)
Ixazomib (MLN9708) capsules
Drug: Dexamethasone
Dexamethasone tablets
Experimental: Ixazomib (MLN9708) + 400 mg/m^2 Cyclophosphamide_NDMM
Ixazomib (MLN9708) 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle until progressive disease (PD)/death or unacceptable toxicity [13 cycles in the Induction Phase continuing in the Maintenance Phase for up to 36 Months] and cyclophosphamide 400 mg/m^2, tablets, orally, Days 1, 8 and 15 of a 28-day cycle for 13 cycles or PD/death or unacceptable toxicity and dexamethasone 40 mg, tablets, orally, Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients >75 years) of a 28-day cycle for 13 cycles or PD/death or unacceptable toxicity in participants with NDMM.
Drug: Cyclophosphamide
Cyclophosphamide tablets
Drug: Ixazomib (MLN9708)
Ixazomib (MLN9708) capsules
Drug: Dexamethasone
Dexamethasone tablets
Experimental: Ixazomib (MLN9708) + 300 mg/m^2 Cyclophosphamide_RRMM
Ixazomib (MLN9708) 4.0 mg, capsules, orally, on Days 1, 8, 15 of a 28-day cycle and cyclophosphamide 300 mg/m^2, tablets, orally, Days 1, 8 and 15 of a 28-day cycle and dexamethasone 40 mg, tablets, orally, Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients >75 years) of a 28-day cycle until PD/death or unacceptable toxicity in participants with RRMM.
Drug: Cyclophosphamide
Cyclophosphamide tablets
Drug: Ixazomib (MLN9708)
Ixazomib (MLN9708) capsules
Drug: Dexamethasone
Dexamethasone tablets

Detailed Description:

The drug being tested in this study is called ixazomib (MLN9708). Ixazomib(MLN9708) is being tested to slow disease progression in people who have newly diagnosed multiple myeloma (NDMM) who are ineligible for high-dose therapy (HDT)-stem cell transplantation (SCT), and also in people who have relapsed and/or refractory multiple myeloma (RRMM) who have received 1 to 3 lines of prior therapy and whose disease is not refractory to proteasome inhibitors. This study will look at disease response rates and safety in people who take ixazomib (MLN9708) in addition to cyclophosphamide and dexamethasone.

The study will enroll approximately 148 patients.

NDMM participants will be randomly assigned (by chance, like flipping a coin) to one of two treatment groups and RRMM participants will be assigned to a third group:

  • NDMM - ixazomib (MLN9708) 4.0 mg + 300 mg/m^2 Cyclophosphamide + dexamethasone
  • NDMM - ixazomib (MLN9708) 4.0 mg + 400 mg/m^2 Cyclophosphamide + dexamethasone
  • RRMM - ixazomib (MLN9708) 4.0 mg + 300 mg/m^2 Cyclophosphamide + dexamethasone

NDMM participants will be asked to take one ixazomib (MLN9708) 4.0 mg capsule on Days 1, 8 and 15 and either a 300 mg/m^2 or 400 mg/m^2 cyclophosphamide tablet on Days 1, 8 and 15 and a dexamethasone 40 mg tablet on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients >75 years) in a 28-day cycle, for a 13-cycle Induction Phase. Participation may continue into a Maintenance Phase if at least stable disease has been reached with an acceptable toxicity profile. Ixazomib (MLN9708) will continue to be administered on Days 1, 8, and 15 in 28-day treatment cycles until disease progression or unacceptable toxicity for up to 36 Months.

RRMM participants will be asked to take one ixazomib (MLN9708) 4.0 mg capsule on Days 1, 8 and 15 and a 300 mg/m^2 cyclophosphamide tablet on Days 1, 8 and 15 and a dexamethasone 40 mg tablet on Days 1, 8, 15 and 22 (dose reduced to 20 mg for patients >75 years) in a 28-day cycle until disease progression or unacceptable toxicity for up to 36 Months.

This multicentre trial will be conducted in EU, US and Australia. Study treatment will continue until disease progression, death, unacceptable toxicity or withdrawal from treatment. At a minimum, the first 6 dose limiting toxicity-evaluable patients in each treatment arm will participate in the safety lead-in portion of the study. All patients will need to make at least 10 visits to the clinic for the first cycle and at least 4 visits n cycles 2 and 3. Starting at cycle 4, all participants will make at least 2 visits to the clinic per cycle, up to cycle 14 for NDMM patients or until treatment discontinuation for RRMM patients. For NDMM patients continuing treatment beyond cycle 14, a visit will occur on day one of every cycle at a minimum. All participants will make an end of treatment visit at the clinic 30 days after the last dose of study drug for safety evaluation. Participants who discontinue treatment before disease progression will continue to be followed and will visit the clinic every 8 weeks until the occurrence of disease progression, death, or consent withdrawal for further follow-up.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Each participant with newly diagnosed multiple myeloma (NDMM) must meet all of the following inclusion criteria to be enrolled in the study:

  1. Adult male or female participants 18 years of age or older with a confirmed diagnosis of symptomatic multiple myeloma (MM) according to standard criteria.
  2. Participants for whom cyclophosphamide and dexamethasone treatment is appropriate and who are considered not eligible for high-dose therapy (HDT)-stem cell transplantation (SCT) for 1 or more of the following reasons:

    • The participant is 65 years of age or older.
    • The participant is less than 65 years of age but has significant comorbid condition(s) that are, in the opinion of the investigator, likely to have a negative impact on tolerability of HDT-SCT.

Each participant with relapsed and/or refractory multiple myeloma (RRMM) must meet all of the following inclusion criteria to be enrolled in the study:

  1. Adult male or female participants 18 years or older with a confirmed diagnosis of symptomatic MM either currently or at the time of initial diagnosis, according to standard criteria, and relapsed and/or refractory disease after 1 to 3 lines of prior therapy. A participant is considered to have refractory disease if disease progression occurred during the treatment period or within 60 days of receiving the last dose of a given therapy. A line of therapy is defined as 1 or more cycles of a single-agent or combination therapy or a sequence of planned treatments such as induction therapy followed by autologous stem cell transplantation (ASCT) and then maintenance therapy.
  2. No evidence of graft-versus-host disease for participants who have undergone prior allogeneic stem cell transplantation.

In addition, all participants (NDMM and RRMM) must meet all of the remaining criteria:

  1. Participants must have measurable disease defined by at least 1 of the following 3 measurements:

    • Serum M-protein ≥ 1 g/dL (≥ 10 g/L).
    • Urine M-protein ≥ 200 mg/24 hours.
    • 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.
  2. Participants must meet all of the following clinical laboratory criteria:

    • Absolute neutrophil count (ANC) ≥ 1000/mm^3 and platelet count ≥ 75,000/mm^3. Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days prior to administration of the study drug.
    • 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 (CrCL) ≥ 30 mL/min.
  3. Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
  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 through 90 days after the last dose of study drug, or
    • agree to practice true abstinence over the period previously described, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [ie, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.), and
    • adhere to any treatment-specific pregnancy prevention guidelines for cyclophosphamide and dexamethasone.
  5. Male participants, even if surgically sterilized (ie, status post-vasectomy), who:

    • 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 over the period previously described, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.), and
    • adhere to any treatment-specific pregnancy prevention guidelines for cyclophosphamide and dexamethasone.
  6. 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.
  7. Suitable venous access for the study-required blood sampling.
  8. Is willing and able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

  1. Prior treatment for multiple myeloma with either standard of care treatment or investigational regimen (for participants with NDMM only).

    NOTE: Prior treatment with corticosteroids (maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone over 14 days. Localized radiation is permitted as long as it is below a therapeutic level and administered at least 14 days prior to the first dose of study treatment.

  2. Diagnosis of smoldering MM, Waldenström's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
  3. Central nervous system involvement.
  4. Diagnosed or treated for another malignancy within 2 years before the first dose 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.
  5. Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of any cause on clinical examination during the Screening period.
  6. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of study drug, including difficulty swallowing.
  7. Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
  8. Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active hepatitis B or C infection.
  9. Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study treatment.
  10. Known allergy to any of the study medications, their analogues, or excipients in the various formulations.
  11. Major surgery within 14 days before the first dose of study drug. (Note: kyphoplasty or vertebroplasty is not considered major surgery.)
  12. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
  13. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  14. 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.
  15. Treatment with any investigational products for reasons other than MM within 30 days before the first dose of study drug.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02046070

Contacts
Contact: For an updated listing of recruitment sites contact: Millennium Medical and Drug Information Center 1-877-674-3784 medical@mlnm.com

Locations
United States, Kentucky
Recruiting
Hazard, Kentucky, United States
United States, Missouri
Recruiting
St. Louis, Missouri, United States
Australia, New South Wales
Not yet recruiting
Camperdown, New South Wales, Australia
Australia, Victoria
Not yet recruiting
Heidelberg, Victoria, Australia
Not yet recruiting
Melbourne, Victoria, Australia
Australia
Not yet recruiting
Adelaide, Australia
Greece
Recruiting
Athens, Attiki, Greece
Poland
Recruiting
L0dz, L0dzkie, Poland
Recruiting
Lublin, Lubelskie, Poland
Not yet recruiting
Gdansk, Pomorskie, Poland
Recruiting
Chorzow, Slaskie, Poland
Sweden
Not yet recruiting
Helsingborg, Skane lan, Sweden
Recruiting
Stockholm, Sodermanlands lan, Sweden
Recruiting
Lund, Sweden
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02046070     History of Changes
Other Study ID Numbers: C16020, 2013-003113-17, U1111-1158-2714
Study First Received: December 12, 2013
Last Updated: October 21, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Greece: Ministry of Health and Welfare
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Sweden: Medical Products Agency

Keywords provided by Millennium Pharmaceuticals, Inc.:
MLN9708
Newly diagnosed
NDMM
IXAZOMIB
RRMM

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Alkylating Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents

ClinicalTrials.gov processed this record on October 29, 2014