Clinical Trial Results:
An Open-Label, Rollover Protocol for Participants Previously Enrolled in Takeda-Sponsored Ixazomib Studies
Summary
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EudraCT number |
2016-001681-28 |
Trial protocol |
ES BE SE GR PL |
Global end of trial date |
03 Jul 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Mar 2025
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First version publication date |
13 Mar 2025
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
C16027
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02924272 | ||
WHO universal trial number (UTN) |
U1111-1184-2041 | ||
Sponsors
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Sponsor organisation name |
Takeda
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Sponsor organisation address |
95 Hayden Avenue, Lexington, MA, United States, 02421
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Public contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Scientific contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Jul 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Jul 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of the trial was to provide continued access of ixazomib and to evaluate the long-term safety profile of ixazomib.
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Protection of trial subjects |
All study participants were required to read and sign an informed consent form (ICF).
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Background therapy |
NA | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
16 Dec 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Canada: 1
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Country: Number of subjects enrolled |
Greece: 4
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Country: Number of subjects enrolled |
Poland: 8
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Country: Number of subjects enrolled |
Singapore: 1
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Country: Number of subjects enrolled |
Spain: 4
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Country: Number of subjects enrolled |
Sweden: 4
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Country: Number of subjects enrolled |
United States: 7
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Country: Number of subjects enrolled |
Korea, Republic of: 1
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Country: Number of subjects enrolled |
Japan: 1
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Worldwide total number of subjects |
32
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EEA total number of subjects |
21
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
7
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From 65 to 84 years |
25
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants took part in the study at various investigative sites globally from 16 December 2016 to 03 July 2024. | |||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Participants who had previously received and tolerated treatment in ixazomib parent studies (C16003, C16005, C16006, C16007, C16008, C16010 Global, C16011, C16013, C16014 Global and Korean Continuation, C16017, C16020, C16029, or C16047), and in investigator’s opinion could benefit from continued therapy were enrolled. | |||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
No
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Arm title
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Ixazomib Monotherapy | |||||||||||||||||||||||||||||||||
Arm description |
Participants received ixazomib capsule, orally, at same dose and schedule as they were receiving in the parent study until disease progression, clinical deterioration in the investigator's judgment, experienced an unacceptable toxicity, withdrew consent, pursued an alternative therapy, meet other study-specified reasons for discontinuation of study drug, or until the participant was transitioned to ixazomib through commercial channels, including reimbursement for the participant's indication, or up to a maximum of 7 years whichever was sooner. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ixazomib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received ixazomib capsule, orally at the same doses as they were receiving in the parent study.
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Arm title
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Ixazomib Combination Therapy | |||||||||||||||||||||||||||||||||
Arm description |
Participants received combination therapy with ixazomib capsule, orally and another medication(s) (1 or more of the anticancer agents dexamethasone, lenalidomide or cyclophosphamide) at same dose and schedule as they were receiving in the parent study until disease progression, clinical deterioration in the investigator's judgment, experienced an unacceptable toxicity, withdrew consent, pursued an alternative therapy, met other study-specified reasons for discontinuation of study drug, or until the participant was transitioned to ixazomib through commercial channels, including reimbursement for the participant's indication, or up to a maximum of 6.5 years whichever was sooner. | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Ixazomib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received combination therapy with ixazomib capsule, orally and another medication(s) (1 or more of the anticancer agents dexamethasone, lenalidomide or cyclophosphamide) at same dose as they were receiving in the parent study.
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Baseline characteristics reporting groups
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Reporting group title |
Ixazomib Monotherapy
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Reporting group description |
Participants received ixazomib capsule, orally, at same dose and schedule as they were receiving in the parent study until disease progression, clinical deterioration in the investigator's judgment, experienced an unacceptable toxicity, withdrew consent, pursued an alternative therapy, meet other study-specified reasons for discontinuation of study drug, or until the participant was transitioned to ixazomib through commercial channels, including reimbursement for the participant's indication, or up to a maximum of 7 years whichever was sooner. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ixazomib Combination Therapy
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Reporting group description |
Participants received combination therapy with ixazomib capsule, orally and another medication(s) (1 or more of the anticancer agents dexamethasone, lenalidomide or cyclophosphamide) at same dose and schedule as they were receiving in the parent study until disease progression, clinical deterioration in the investigator's judgment, experienced an unacceptable toxicity, withdrew consent, pursued an alternative therapy, met other study-specified reasons for discontinuation of study drug, or until the participant was transitioned to ixazomib through commercial channels, including reimbursement for the participant's indication, or up to a maximum of 6.5 years whichever was sooner. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ixazomib Monotherapy
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Reporting group description |
Participants received ixazomib capsule, orally, at same dose and schedule as they were receiving in the parent study until disease progression, clinical deterioration in the investigator's judgment, experienced an unacceptable toxicity, withdrew consent, pursued an alternative therapy, meet other study-specified reasons for discontinuation of study drug, or until the participant was transitioned to ixazomib through commercial channels, including reimbursement for the participant's indication, or up to a maximum of 7 years whichever was sooner. | ||
Reporting group title |
Ixazomib Combination Therapy
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Reporting group description |
Participants received combination therapy with ixazomib capsule, orally and another medication(s) (1 or more of the anticancer agents dexamethasone, lenalidomide or cyclophosphamide) at same dose and schedule as they were receiving in the parent study until disease progression, clinical deterioration in the investigator's judgment, experienced an unacceptable toxicity, withdrew consent, pursued an alternative therapy, met other study-specified reasons for discontinuation of study drug, or until the participant was transitioned to ixazomib through commercial channels, including reimbursement for the participant's indication, or up to a maximum of 6.5 years whichever was sooner. |
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End point title |
Number of Participants With Serious Adverse Events (SAEs) [1] | |||||||||
End point description |
An adverse event (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. An AE can therefore be 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. An SAE is any untoward medical occurrence that at any dose: a) results in death; b) is life-threatening; c) requires inpatient hospitalization or prolongation of an existing hospitalization; d) results in persistent or significant disability or incapacity; e) is a congenital anomaly/birth defect; f) is a medically important event. Safety Population included all enrolled participants who received at least 1 dose of ixazomib.
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End point type |
Primary
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End point timeframe |
Up to 7 years
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive analyses were planned for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Number of Participants With ≥ Grade 3 AEs [2] | |||||||||
End point description |
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. The severity grade was evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL), Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5 was: death related to AE. Safety Population included all enrolled participants who received at least 1 dose of ixazomib.
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End point type |
Primary
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End point timeframe |
Up to 7 years
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive analyses were planned for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Number of Participants With ≥ Grade 2 Peripheral Neuropathy [3] | |||||||||
End point description |
Severity grade was evaluated based on CTCAE version 5.0. Grade 2: moderate symptoms; limiting instrumental activities of daily living. Grade 3: severe or medically significant; limiting self-care activities of daily living. Grade 4: life threatening consequences; urgent intervention indicated. Safety Population included all enrolled participants who received at least 1 dose of ixazomib.
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End point type |
Primary
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End point timeframe |
Up to 7 years
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive analyses were planned for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Number of Participants With New Primary Malignancies [4] | |||||||||
End point description |
Safety Population included all enrolled participants who received at least 1 dose of ixazomib.
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End point type |
Primary
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End point timeframe |
Up to 7 years
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive analyses were planned for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Number of Participants With any AE Resulting in Dose Modification or Discontinuation of any Study Drug [5] | |||||||||||||||
End point description |
An AE means 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. An AE can therefore be 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. Safety Population included all enrolled participants who received at least 1 dose of ixazomib.
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End point type |
Primary
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End point timeframe |
Up to 7 years
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive analyses were planned for this endpoint. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Up to 7 years
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Adverse event reporting additional description |
The Safety Population included all enrolled participants who received at least 1 dose of ixazomib.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
Ixazomib Monotherapy
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Reporting group description |
Participants received ixazomib capsule, orally, at same dose and schedule as they were receiving in the parent study until disease progression, clinical deterioration in the investigator's judgment, experienced an unacceptable toxicity, withdrew consent, pursued an alternative therapy, meet other study-specified reasons for discontinuation of study drug, or until the participant was transitioned to ixazomib through commercial channels, including reimbursement for the participant's indication, or up to a maximum of 7 years whichever was sooner. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ixazomib Combination Therapy
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Reporting group description |
Participants received combination therapy with ixazomib capsule, orally and another medication(s) (1 or more of the anticancer agents dexamethasone, lenalidomide or cyclophosphamide) at same dose and schedule as they were receiving in the parent study until disease progression, clinical deterioration in the investigator's judgment, experienced an unacceptable toxicity, withdrew consent, pursued an alternative therapy, met other study-specified reasons for discontinuation of study drug, or until the participant was transitioned to ixazomib through commercial channels, including reimbursement for the participant's indication, or up to a maximum of 6.5 years whichever was sooner. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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23 Mar 2017 |
The following changes were made as per Amendment 01: 1. Added allowance for study drug administration to be rounded and/or converted from body surface area (BSA)-based dosing to fixed dosing with approval from the medical monitor. 2. Specified that local safety-related laboratory and vital signs assessments would be performed as presented in this study, rather than in the parent study. 3. Provided additional dose administration instructions. 4. Updated storage and handling instructions to be consistent with current ixazomib investigator’s brochure (IB). 5. Added allowance for on-site monitoring visits. 6. Added allowance for study drug to be dispensed for up to 3 cycles at a distribution at the discretion of the investigator. |
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03 Jun 2021 |
The following changes were made as per Amendment 03: 1. Updated the background information on other ixazomib clinical trials. 2. Updated the criteria for withdrawing participants from study. 3. Added information about alternative monitoring approaches, such as remote source data verification, in the event a monitor could not visit the site in a timely manner due to the coronavirus disease 2019 (COVID-19) pandemic. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |