Ixazomib Plus Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Relapsed/Refractory Multiple Myeloma

Sponsor
City of Hope Medical Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02119468
Collaborator
National Cancer Institute (NCI) (NIH)
32
Enrollment
5
Locations
2
Arms
90.1
Anticipated Duration (Months)
6.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of ixazomib and to see how well it works when given together with pomalidomide and dexamethasone in treating patients with relapsed or relapsed/refractory multiple myeloma. Ixazomib may stop the growth of cancer by interfering with proteasomes (the protein breakdown mechanism in the cells). Pomalidomide and dexamethasone can modify and regulate the immune system and may stop cancer cells from growing. Giving ixazomib with pomalidomide and dexamethasone may be an effective treatment for relapsed or relapsed/refractory multiple myeloma.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To determine the recommended phase II dose (RP2D) of MLN9708 (ixazomib), when given in combination with pomalidomide and dexamethasone, in patients with relapsed or relapsed/refractory multiple myeloma. (Phase I) II. To estimate the response rate and to evaluate the antitumor activity of the three drug combination: MLN9708 (at the RP2D), pomalidomide and dexamethasone, in patients with relapsed or relapsed/refractory multiple myeloma. (Phase II)
SECONDARY OBJECTIVES:
  1. To evaluate the safety of MLN9708 at each dose level when given as part of a three drug combination by assessing the following: type, frequency, severity, attribution, time course and duration of adverse events; and clinical laboratory tests at various points in the study. (Phase I) II. To characterize and evaluate toxicities, including type, frequency, severity, attribution, time course and duration, at the RP2D, for the three drug combination. (Phase
    1. To obtain estimates of response duration, depth of response, clinical benefit response, and survival (overall and progression-free), at the RP2D, for the three drug combination. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of ixazomib followed by a phase II study.

Patients receive ixazomib orally (PO) on days 1, 8, and 15; dexamethasone PO on days 1, 8, 15, and 22; and pomalidomide PO on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I/II Trial of MLN9708 Plus Pomalidomide and Dexamethasone for Relapsed or Relapsed Refractory Multiple Myeloma
Actual Study Start Date :
Jun 30, 2014
Actual Primary Completion Date :
May 18, 2016
Anticipated Study Completion Date :
Dec 31, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Treatment (3mg MLN9708)

Patients receive 3mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: ixazomib citrate
Given orally
Other Names:
  • MLN9708
  • proteasome inhibitor MLN9708
  • Drug: dexamethasone
    Given orally
    Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
  • Drug: pomalidomide
    Given orally
    Other Names:
  • CC-4047
  • Pomalyst
  • Experimental: Treatment (4mg MLN9708)

    Patients receive 4mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: ixazomib citrate
    Given orally
    Other Names:
  • MLN9708
  • proteasome inhibitor MLN9708
  • Drug: dexamethasone
    Given orally
    Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
  • Drug: pomalidomide
    Given orally
    Other Names:
  • CC-4047
  • Pomalyst
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Patients With Dose-Limiting Toxicities (Phase I) [From the initial treatment to Day 28 (Cycle #1)]

      Dose Limiting Toxicity (DLT) is defined as any of the toxicities in Section 7.3 that are at least possibly related to either Pomalidomide or MLN9708 that occur during cycle 1. Toxicity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.03. The highest dose level that produces 1/6 dose-limiting toxicities (DLTs) in course 1 will be the maximum tolerated dose (MTD). The RP2D of ixazomib and pomalidomide will generally be the MTD, but it may be less than the MTD based on a review of available data/cumulative toxicities from phase I.

    2. Overall Response Rate at the Recommended Phase II Dose (RP2D) [From the initial treatment to 24 months]

      Over response rate is calculated as the percent of evaluable patients that have confirmed stringent complete remission (sCR), complete remission (CR), very good partial remission (VGPR) or partial remission [PR]) per modified IMWG criteria. sCR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow. CR defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR defined as serum and urine M-protein detectable or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h. PR defined as > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h. The exact 95% confidence intervals are calculated for the estimate.

    3. Maximum Tolerated Dose (MTD) of MLN9708 (Phase I) [From the initial treatment to Day 28 (Cycle #1)]

      The highest dose level that produces 1/6 dose-limiting toxicities (DLTs) in Cycle #1 will be the maximum tolerated dose (MTD). The RP2D of ixazomib and pomalidomide will generally be the MTD, but it may be less than the MTD based on a review of available data/cumulative toxicities from phase I.

    Secondary Outcome Measures

    1. Duration of Response at the Recommended Phase II Dose (RP2D) [Time interval from the date of first documented response (sCR/CR/VGPR or PR) to documented disease relapse, progression or death whichever occurs first, up to 24 months]

      Time from the date of first documented response (sCR/CR/VGPR or PR) to documented disease relapse, progression or death whichever occurs first. sCR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow. CR defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR defined as serum and urine M-protein detectable or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h. PR defined as > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h.

    2. Clinical Benefit Response Rate at the Recommended Phase II Dose (RP2D) [From the initial treatment up to 24 months]

      Clinical benefit response rate is calculated as the percent of evaluable patients that have confirmed stringent complete remission (sCR), complete remission (CR), very good partial remission (VGPR), partial remission (PR), minimal response (MR) or stable disease (SD) per modified IMWG criteria. The exact 95% confidence intervals are calculated for the estimate.

    3. One-Year Overall Survival at the Recommended Phase II Dose (RP2D) [Date of first dose of study drug to date of death from any cause, up to 24 months. And the median follow-up for the surviving patients is at least one year.]

      Overall survival (OS) was measured from initial treatment to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula. [Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.]

    4. One-Year Progression-Free Survival at the Recommend Phase II Dose (RP2D) [Date of first dose of study drug to first documented disease relapse, progression or death from any cause, whichever occurs first, up to 24 months. And the median follow-up for the surviving patients is at least one year.]

      Progression-free survival (PFS) was defined as time from initial treatment to recurrence, progression or death. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works. Progression-free survival was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula [Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Voluntary written informed 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 patient at any time without prejudice to future medical care

    • Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to and again within 24 hours of starting pomalidomide or MLN9708 and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide or MLN9708 through 90 days after the last dose of study drug; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy from the time of signing the informed consent form through 90 days after the last dose of study drug; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure

    • All patients enrolled into this trial, must be registered in and must comply with all requirements of the POMALYST (pomalidomide) Risk Evaluation and Mitigation Strategy (REMS) program

    • Patients must have a diagnosis of relapsed or relapsed and refractory multiple myeloma with a minimum of one prior regimen and a maximum of 5 prior regimens

    • Patients must have had therapy with a proteasome inhibitor and lenalidomide and be refractory to lenalidomide according to the International Myeloma Working Group (IMWG) criteria definition of refractory disease (progressive disease on or within 60 days of stopping lenalidomide)

    • Patients must have measurable disease defined as one of the following:

    • Serum M protein >= 0.5 g/dL

    • Urine M protein >= 200 mg/24 hours

    • Serum free light chain >= 10 mg/dL provided the free light chain (FLC) ratio is abnormal

    • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

    • Absolute neutrophil count (ANC) >= 1,000/mm^3

    • Platelet count >= 75,000/uL for patients in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count >= 50,000/uL for patients in whom >= 50% of bone marrow nucleated cells are plasma cells; platelet transfusions are not allowed within 3 days of last platelet assessment to confirm eligibility

    • Total bilirubin =< 1.5 × the institutional upper limit of the normal range (IULN)

    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 × IULN

    • Calculated creatinine clearance >= 45 mL/min

    Exclusion Criteria:
    • Female patients who are pregnant or breastfeeding or have a positive serum pregnancy test during the screening period

    • Failure to have fully recovered (ie, =< grade 1 toxicity) from the reversible effects of prior chemotherapy

    • Prior therapy with a combination regimen containing pomalidomide except the 2 drug combination of pomalidomide and dexamethasone

    • 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 MLN9708

    • 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 MLN9708, with strong inhibitors of cytochrome P450, family 1, subfamily A, polypeptide 2 (CYP1A2) (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P450, family 3, subfamily A (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

    • Unable or unwilling to undergo antithrombotic prophylaxis

    • Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive

    • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol

    • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent

    • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 or pomalidomide including difficulty swallowing

    • Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy with evidence of residual disease; patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection

    • Patient has > grade 2 peripheral neuropathy on clinical examination during the screening period

    • Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21 days of the start of this trial and throughout the duration of this trial (for all other standard therapies, no treatment within 14 days of the start of this trial)

    • Patients who are pomalidomide refractory, defined as patients who progress on or within 60 days of pomalidomide when given as a single agent or with dexamethasone

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Mayo ClinicScottsdaleArizonaUnited States85259
    2City of Hope Medical CenterDuarteCaliforniaUnited States91010
    3Emory University/Winship Cancer InstituteAtlantaGeorgiaUnited States30322
    4Mayo ClinicRochesterMinnesotaUnited States55905
    5Sarah Cannon Research Institute (SCRI)NashvilleTennesseeUnited States37203

    Sponsors and Collaborators

    • City of Hope Medical Center
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Amrita Krishnan, City of Hope Medical Center

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    City of Hope Medical Center
    ClinicalTrials.gov Identifier:
    NCT02119468
    Other Study ID Numbers:
    • 12267
    • NCI-2014-00803
    • 12267
    First Posted:
    Apr 21, 2014
    Last Update Posted:
    Sep 16, 2021
    Last Verified:
    May 1, 2021

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleDose Level #1 (3mg MLN9708)Dose Level #2 (4mg MLN9708)
    Arm/Group DescriptionPatients receive ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ixazomib citrate: Given orally dexamethasone: Given orally pomalidomide: Given orallyPatients receive ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Period Title: Overall Study
    STARTED725
    COMPLETED725
    NOT COMPLETED00

    Baseline Characteristics

    Arm/Group TitleDose Level #1 (3mg MLN9708)Dose Level #2 (4mg MLN9708)Total
    Arm/Group DescriptionPatients receive ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ixazomib citrate: Given orally dexamethasone: Given orally pomalidomide: Given orallyPatients receive ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ixazomib citrate: Given orally dexamethasone: Given orally pomalidomide: Given orallyTotal of all reporting groups
    Overall Participants72532
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    53
    63
    62
    Sex: Female, Male (Count of Participants)
    Female
    2
    28.6%
    10
    40%
    12
    37.5%
    Male
    5
    71.4%
    15
    60%
    20
    62.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    14.3%
    1
    4%
    2
    6.3%
    Not Hispanic or Latino
    6
    85.7%
    23
    92%
    29
    90.6%
    Unknown or Not Reported
    0
    0%
    1
    4%
    1
    3.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    2
    8%
    2
    6.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    3
    12%
    3
    9.4%
    White
    7
    100%
    20
    80%
    27
    84.4%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    7
    100%
    25
    100%
    32
    100%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Patients With Dose-Limiting Toxicities (Phase I)
    DescriptionDose Limiting Toxicity (DLT) is defined as any of the toxicities in Section 7.3 that are at least possibly related to either Pomalidomide or MLN9708 that occur during cycle 1. Toxicity graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.03. The highest dose level that produces 1/6 dose-limiting toxicities (DLTs) in course 1 will be the maximum tolerated dose (MTD). The RP2D of ixazomib and pomalidomide will generally be the MTD, but it may be less than the MTD based on a review of available data/cumulative toxicities from phase I.
    Time FrameFrom the initial treatment to Day 28 (Cycle #1)

    Outcome Measure Data

    Analysis Population Description
    Patients were considered evaluable for DLT if receiving at least 75% of both Pomalidomide and MLN9708 and followed for the full 28 days during cycle 1 or experience a DLT. All patients who are not evaluable for DLT were replaced.
    Arm/Group TitleDose Level #1: 3mg MLN9708Dose Level #2: 4mg MLN9708
    Arm/Group DescriptionPatients receive ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.Patients receive ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants66
    Count of Participants [Participants]
    1
    14.3%
    1
    4%
    2. Primary Outcome
    TitleOverall Response Rate at the Recommended Phase II Dose (RP2D)
    DescriptionOver response rate is calculated as the percent of evaluable patients that have confirmed stringent complete remission (sCR), complete remission (CR), very good partial remission (VGPR) or partial remission [PR]) per modified IMWG criteria. sCR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow. CR defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR defined as serum and urine M-protein detectable or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h. PR defined as > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h. The exact 95% confidence intervals are calculated for the estimate.
    Time FrameFrom the initial treatment to 24 months

    Outcome Measure Data

    Analysis Population Description
    Patients received 4 mg MLN9708, 4mg pomalidomide, and 40 mg dexamethasone (RP2D).
    Arm/Group TitleDose Level #2 (4mg MLN9708)
    Arm/Group DescriptionPatients receive 4mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants25
    Number (95% Confidence Interval) [Percentage of Participants (%)]
    48
    685.7%
    3. Primary Outcome
    TitleMaximum Tolerated Dose (MTD) of MLN9708 (Phase I)
    DescriptionThe highest dose level that produces 1/6 dose-limiting toxicities (DLTs) in Cycle #1 will be the maximum tolerated dose (MTD). The RP2D of ixazomib and pomalidomide will generally be the MTD, but it may be less than the MTD based on a review of available data/cumulative toxicities from phase I.
    Time FrameFrom the initial treatment to Day 28 (Cycle #1)

    Outcome Measure Data

    Analysis Population Description
    6 patients treated at dose level #2 in Phase I are evaluable for dose limiting toxicity.
    Arm/Group TitleDose Level #2 (4mg MLN9708)
    Arm/Group DescriptionPatients receive 4mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants6
    Number [mg]
    4
    4. Secondary Outcome
    TitleDuration of Response at the Recommended Phase II Dose (RP2D)
    DescriptionTime from the date of first documented response (sCR/CR/VGPR or PR) to documented disease relapse, progression or death whichever occurs first. sCR as defined below plus normal FLC ratio and absence of clonal cells in bone marrow. CR defined as negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. VGPR defined as serum and urine M-protein detectable or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h. PR defined as > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or to < 200 mg/24 h.
    Time FrameTime interval from the date of first documented response (sCR/CR/VGPR or PR) to documented disease relapse, progression or death whichever occurs first, up to 24 months

    Outcome Measure Data

    Analysis Population Description
    Patients received 4 mg MLN9708, 4mg pomalidomide, and 40 mg dexamethasone (RP2D).
    Arm/Group TitleDose Level #2 (4mg MLN9708)
    Arm/Group DescriptionPatients receive 4mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants25
    Median (Full Range) [Months]
    9.2
    5. Secondary Outcome
    TitleClinical Benefit Response Rate at the Recommended Phase II Dose (RP2D)
    DescriptionClinical benefit response rate is calculated as the percent of evaluable patients that have confirmed stringent complete remission (sCR), complete remission (CR), very good partial remission (VGPR), partial remission (PR), minimal response (MR) or stable disease (SD) per modified IMWG criteria. The exact 95% confidence intervals are calculated for the estimate.
    Time FrameFrom the initial treatment up to 24 months

    Outcome Measure Data

    Analysis Population Description
    Patients received 4 mg MLN9708, 4mg pomalidomide, and 40 mg dexamethasone (RP2D).
    Arm/Group TitleDose Level #2 (4mg MLN9708)
    Arm/Group DescriptionPatients receive 4mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants25
    Number (95% Confidence Interval) [Percentage of Participants (%)]
    76
    1085.7%
    6. Secondary Outcome
    TitleOne-Year Overall Survival at the Recommended Phase II Dose (RP2D)
    DescriptionOverall survival (OS) was measured from initial treatment to death from any cause. It was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula. [Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.]
    Time FrameDate of first dose of study drug to date of death from any cause, up to 24 months. And the median follow-up for the surviving patients is at least one year.

    Outcome Measure Data

    Analysis Population Description
    Patients received 4 mg MLN9708, 4mg pomalidomide, and 40 mg dexamethasone (RP2D).
    Arm/Group TitleDose Level #2 (4mg MLN9708)
    Arm/Group DescriptionPatients receive 4mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants25
    Number (95% Confidence Interval) [Percentage of Participants (%)]
    82
    1171.4%
    7. Secondary Outcome
    TitleOne-Year Progression-Free Survival at the Recommend Phase II Dose (RP2D)
    DescriptionProgression-free survival (PFS) was defined as time from initial treatment to recurrence, progression or death. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works. Progression-free survival was estimated using the Kaplan-Meier method; the 95% confidence interval was calculated using Greenwood's formula [Breslow NE, Day NE. Statistical methods in cancer research: volume II, the design and analysis of cohort studies. IARC Sci Publ 1987;82:1-406.]
    Time FrameDate of first dose of study drug to first documented disease relapse, progression or death from any cause, whichever occurs first, up to 24 months. And the median follow-up for the surviving patients is at least one year.

    Outcome Measure Data

    Analysis Population Description
    Patients received 4 mg MLN9708, 4mg pomalidomide, and 40 mg dexamethasone (RP2D).
    Arm/Group TitleDose Level #2 (4mg MLN9708)
    Arm/Group DescriptionPatients receive 4mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
    Measure Participants25
    Number (95% Confidence Interval) [Percentage of Participants (%)]
    34
    485.7%

    Adverse Events

    Time FrameFrom the date of the first dose up to 2 years
    Adverse Event Reporting Description
    Arm/Group TitleDose Level #1 (3mg MLN9708)Dose Level #2 (4mg MLN9708)
    Arm/Group DescriptionPatients receive 3mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ixazomib citrate: Given orally dexamethasone: Given orally pomalidomide: Given orallyPatients receive 4mg ixazomib citrate (MLN9708) orally on days 1, 8, and 15; dexamethasone orally on days 1, 8, 15, and 22; and pomalidomide orally on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. ixazomib citrate: Given orally dexamethasone: Given orally pomalidomide: Given orally
    All Cause Mortality
    Dose Level #1 (3mg MLN9708)Dose Level #2 (4mg MLN9708)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total4/7 (57.1%) 6/25 (24%)
    Serious Adverse Events
    Dose Level #1 (3mg MLN9708)Dose Level #2 (4mg MLN9708)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total4/7 (57.1%) 11/25 (44%)
    Blood and lymphatic system disorders
    Anemia1/7 (14.3%) 10/25 (0%) 0
    Febrile neutropenia0/7 (0%) 02/25 (8%) 2
    Cardiac disorders
    Sinus tachycardia1/7 (14.3%) 10/25 (0%) 0
    Heart failure0/7 (0%) 01/25 (4%) 1
    Gastrointestinal disorders
    Rectal hemorrhage0/7 (0%) 01/25 (4%) 1
    Small intestinal obstruction0/7 (0%) 01/25 (4%) 1
    General disorders
    Death NOS0/7 (0%) 01/25 (4%) 1
    Fever0/7 (0%) 01/25 (4%) 1
    Infections and infestations
    Skin infection1/7 (14.3%) 10/25 (0%) 0
    Lung infection2/7 (28.6%) 22/25 (8%) 4
    Sepsis0/7 (0%) 01/25 (4%) 1
    Upper respiratory infection0/7 (0%) 01/25 (4%) 1
    Injury, poisoning and procedural complications
    Spinal fracture0/7 (0%) 01/25 (4%) 1
    Investigations
    Neutrophil count decreased0/7 (0%) 01/25 (4%) 1
    Musculoskeletal and connective tissue disorders
    Back pain1/7 (14.3%) 10/25 (0%) 0
    Muscle weakness lower limb1/7 (14.3%) 10/25 (0%) 0
    Buttock pain0/7 (0%) 01/25 (4%) 1
    Reproductive system and breast disorders
    Pelvic pain0/7 (0%) 01/25 (4%) 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnea1/7 (14.3%) 11/25 (4%) 1
    Respiratory, thoracic and mediastinal disorders - Other, specify1/7 (14.3%) 10/25 (0%) 0
    Hypoxia0/7 (0%) 01/25 (4%) 1
    Pneumonitis0/7 (0%) 01/25 (4%) 1
    Respiratory failure0/7 (0%) 01/25 (4%) 1
    Other (Not Including Serious) Adverse Events
    Dose Level #1 (3mg MLN9708)Dose Level #2 (4mg MLN9708)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total7/7 (100%) 25/25 (100%)
    Blood and lymphatic system disorders
    Anemia6/7 (85.7%) 1719/25 (76%) 88
    Blood and lymphatic system disorders - Other, specify0/7 (0%) 01/25 (4%) 1
    Thrombotic thrombocytopenic purpura1/7 (14.3%) 11/25 (4%) 1
    Cardiac disorders
    Atrial fibrillation1/7 (14.3%) 11/25 (4%) 2
    Heart failure0/7 (0%) 01/25 (4%) 2
    Paroxysmal atrial tachycardia1/7 (14.3%) 10/25 (0%) 0
    Sinus bradycardia1/7 (14.3%) 81/25 (4%) 4
    Sinus tachycardia2/7 (28.6%) 52/25 (8%) 2
    Tricuspid valve disease0/7 (0%) 01/25 (4%) 1
    Ear and labyrinth disorders
    Ear and labyrinth disorders - Other, specify0/7 (0%) 01/25 (4%) 2
    Hearing impaired0/7 (0%) 01/25 (4%) 1
    Vertigo0/7 (0%) 01/25 (4%) 1
    Eye disorders
    Blurred vision1/7 (14.3%) 25/25 (20%) 24
    Cataract1/7 (14.3%) 10/25 (0%) 0
    Dry eye0/7 (0%) 01/25 (4%) 1
    Eye disorders - Other, specify0/7 (0%) 01/25 (4%) 11
    Eye pain0/7 (0%) 01/25 (4%) 1
    Photophobia1/7 (14.3%) 20/25 (0%) 0
    Gastrointestinal disorders
    Abdominal distension0/7 (0%) 01/25 (4%) 2
    Abdominal pain1/7 (14.3%) 13/25 (12%) 13
    Bloating0/7 (0%) 01/25 (4%) 1
    Constipation2/7 (28.6%) 210/25 (40%) 35
    Diarrhea4/7 (57.1%) 49/25 (36%) 20
    Dry mouth2/7 (28.6%) 41/25 (4%) 1
    Dyspepsia1/7 (14.3%) 34/25 (16%) 8
    Fecal incontinence0/7 (0%) 01/25 (4%) 1
    Flatulence0/7 (0%) 01/25 (4%) 1
    Gastrointestinal disorders - Other, specify0/7 (0%) 03/25 (12%) 3
    Hemorrhoidal hemorrhage1/7 (14.3%) 10/25 (0%) 0
    Hemorrhoids1/7 (14.3%) 10/25 (0%) 0
    Mucositis oral0/7 (0%) 03/25 (12%) 3
    Nausea3/7 (42.9%) 810/25 (40%) 26
    Vomiting2/7 (28.6%) 45/25 (20%) 9
    General disorders
    Chills2/7 (28.6%) 33/25 (12%) 3
    Edema face0/7 (0%) 01/25 (4%) 1
    Edema limbs2/7 (28.6%) 36/25 (24%) 22
    Fatigue5/7 (71.4%) 1015/25 (60%) 79
    Fever3/7 (42.9%) 63/25 (12%) 6
    Flu like symptoms2/7 (28.6%) 41/25 (4%) 1
    Gait disturbance1/7 (14.3%) 11/25 (4%) 1
    General disorders and administration site conditions - Other, specify1/7 (14.3%) 21/25 (4%) 1
    Localized edema0/7 (0%) 01/25 (4%) 1
    Malaise1/7 (14.3%) 10/25 (0%) 0
    Non-cardiac chest pain1/7 (14.3%) 12/25 (8%) 2
    Pain1/7 (14.3%) 13/25 (12%) 4
    Infections and infestations
    Bronchial infection1/7 (14.3%) 11/25 (4%) 2
    Infections and infestations - Other, specify0/7 (0%) 03/25 (12%) 5
    Lung infection1/7 (14.3%) 22/25 (8%) 2
    Nail infection1/7 (14.3%) 11/25 (4%) 1
    Otitis media1/7 (14.3%) 10/25 (0%) 0
    Rhinitis infective0/7 (0%) 02/25 (8%) 2
    Sinusitis1/7 (14.3%) 12/25 (8%) 3
    Upper respiratory infection1/7 (14.3%) 27/25 (28%) 12
    Injury, poisoning and procedural complications
    Bruising1/7 (14.3%) 42/25 (8%) 5
    Fall0/7 (0%) 03/25 (12%) 7
    Fracture0/7 (0%) 01/25 (4%) 1
    Investigations
    Alanine aminotransferase increased3/7 (42.9%) 81/25 (4%) 17
    Alkaline phosphatase increased1/7 (14.3%) 12/25 (8%) 2
    Aspartate aminotransferase increased3/7 (42.9%) 121/25 (4%) 4
    Blood bilirubin increased3/7 (42.9%) 54/25 (16%) 13
    CD4 lymphocytes decreased0/7 (0%) 01/25 (4%) 1
    Cardiac troponin I increased0/7 (0%) 01/25 (4%) 1
    Creatinine increased4/7 (57.1%) 114/25 (16%) 21
    Ejection fraction decreased0/7 (0%) 01/25 (4%) 1
    Electrocardiogram QT corrected interval prolonged1/7 (14.3%) 10/25 (0%) 0
    INR increased1/7 (14.3%) 201/25 (4%) 2
    Investigations - Other, specify0/7 (0%) 01/25 (4%) 2
    Lymphocyte count decreased6/7 (85.7%) 2413/25 (52%) 46
    Neutrophil count decreased5/7 (71.4%) 3917/25 (68%) 105
    Platelet count decreased5/7 (71.4%) 4319/25 (76%) 95
    Weight gain2/7 (28.6%) 222/25 (8%) 10
    Weight loss0/7 (0%) 02/25 (8%) 3
    White blood cell decreased6/7 (85.7%) 4016/25 (64%) 83
    Metabolism and nutrition disorders
    Acidosis1/7 (14.3%) 10/25 (0%) 0
    Alkalosis1/7 (14.3%) 10/25 (0%) 0
    Anorexia1/7 (14.3%) 11/25 (4%) 2
    Dehydration0/7 (0%) 03/25 (12%) 4
    Hypercalcemia1/7 (14.3%) 23/25 (12%) 4
    Hyperglycemia1/7 (14.3%) 511/25 (44%) 20
    Hyperkalemia2/7 (28.6%) 30/25 (0%) 0
    Hypermagnesemia2/7 (28.6%) 20/25 (0%) 0
    Hypernatremia1/7 (14.3%) 10/25 (0%) 0
    Hypertriglyceridemia1/7 (14.3%) 10/25 (0%) 0
    Hyperuricemia1/7 (14.3%) 21/25 (4%) 2
    Hypoalbuminemia4/7 (57.1%) 65/25 (20%) 17
    Hypocalcemia3/7 (42.9%) 116/25 (24%) 16
    Hypoglycemia1/7 (14.3%) 132/25 (8%) 9
    Hypokalemia3/7 (42.9%) 64/25 (16%) 15
    Hypomagnesemia0/7 (0%) 02/25 (8%) 2
    Hyponatremia4/7 (57.1%) 105/25 (20%) 21
    Hypophosphatemia2/7 (28.6%) 41/25 (4%) 1
    Obesity2/7 (28.6%) 203/25 (12%) 13
    Tumor lysis syndrome1/7 (14.3%) 10/25 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia1/7 (14.3%) 12/25 (8%) 3
    Arthritis0/7 (0%) 01/25 (4%) 1
    Back pain3/7 (42.9%) 58/25 (32%) 14
    Bone pain1/7 (14.3%) 13/25 (12%) 3
    Flank pain0/7 (0%) 01/25 (4%) 1
    Generalized muscle weakness1/7 (14.3%) 36/25 (24%) 34
    Muscle weakness lower limb0/7 (0%) 03/25 (12%) 5
    Musculoskeletal and connective tissue disorder - Other, specify1/7 (14.3%) 25/25 (20%) 17
    Myalgia0/7 (0%) 03/25 (12%) 29
    Neck pain1/7 (14.3%) 12/25 (8%) 3
    Pain in extremity2/7 (28.6%) 77/25 (28%) 12
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify1/7 (14.3%) 10/25 (0%) 0
    Nervous system disorders
    Amnesia0/7 (0%) 02/25 (8%) 15
    Dizziness3/7 (42.9%) 58/25 (32%) 15
    Dysgeusia0/7 (0%) 03/25 (12%) 3
    Headache1/7 (14.3%) 35/25 (20%) 6
    Nervous system disorders - Other, specify0/7 (0%) 02/25 (8%) 4
    Neuralgia1/7 (14.3%) 20/25 (0%) 0
    Peripheral motor neuropathy0/7 (0%) 01/25 (4%) 1
    Peripheral sensory neuropathy4/7 (57.1%) 2012/25 (48%) 59
    Somnolence1/7 (14.3%) 11/25 (4%) 7
    Syncope0/7 (0%) 03/25 (12%) 3
    Tremor1/7 (14.3%) 122/25 (8%) 17
    Psychiatric disorders
    Agitation0/7 (0%) 01/25 (4%) 1
    Anxiety1/7 (14.3%) 11/25 (4%) 7
    Confusion0/7 (0%) 05/25 (20%) 36
    Depression1/7 (14.3%) 11/25 (4%) 1
    Insomnia1/7 (14.3%) 125/25 (20%) 17
    Mania1/7 (14.3%) 10/25 (0%) 0
    Renal and urinary disorders
    Acute kidney injury0/7 (0%) 01/25 (4%) 1
    Chronic kidney disease1/7 (14.3%) 52/25 (8%) 6
    Hematuria1/7 (14.3%) 10/25 (0%) 0
    Proteinuria5/7 (71.4%) 505/25 (20%) 37
    Reproductive system and breast disorders
    Irregular menstruation0/7 (0%) 01/25 (4%) 1
    Pelvic pain0/7 (0%) 01/25 (4%) 1
    Reproductive system and breast disorders - Other, specify0/7 (0%) 01/25 (4%) 1
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis0/7 (0%) 02/25 (8%) 2
    Atelectasis1/7 (14.3%) 11/25 (4%) 1
    Cough2/7 (28.6%) 25/25 (20%) 10
    Dyspnea3/7 (42.9%) 56/25 (24%) 45
    Epistaxis1/7 (14.3%) 12/25 (8%) 3
    Hiccups0/7 (0%) 03/25 (12%) 5
    Hypoxia2/7 (28.6%) 20/25 (0%) 0
    Nasal congestion1/7 (14.3%) 24/25 (16%) 6
    Pleuritic pain1/7 (14.3%) 10/25 (0%) 0
    Postnasal drip0/7 (0%) 01/25 (4%) 1
    Productive cough2/7 (28.6%) 31/25 (4%) 3
    Sinus disorder0/7 (0%) 01/25 (4%) 1
    Wheezing2/7 (28.6%) 20/25 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia2/7 (28.6%) 30/25 (0%) 0
    Dry skin0/7 (0%) 02/25 (8%) 14
    Hyperhidrosis1/7 (14.3%) 12/25 (8%) 4
    Pruritus3/7 (42.9%) 46/25 (24%) 16
    Rash maculo-papular2/7 (28.6%) 35/25 (20%) 6
    Skin and subcutaneous tissue disorders - Other, specify1/7 (14.3%) 25/25 (20%) 16
    Vascular disorders
    Hot flashes1/7 (14.3%) 10/25 (0%) 0
    Hypertension4/7 (57.1%) 1227/25 (28%) 42
    Hypotension0/7 (0%) 05/25 (20%) 7

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleDr. Amrita Krishnan
    OrganizationCity of Hope National Medical Center
    Phone626-256-4673 ext 62405
    EmailAKrishnan@coh.org
    Responsible Party:
    City of Hope Medical Center
    ClinicalTrials.gov Identifier:
    NCT02119468
    Other Study ID Numbers:
    • 12267
    • NCI-2014-00803
    • 12267
    First Posted:
    Apr 21, 2014
    Last Update Posted:
    Sep 16, 2021
    Last Verified:
    May 1, 2021