Multiple MyelomaPhase 1NCT01830816
Pharmacokinetics Study of Oral Ixazomib (MLN9708) in Relapsed/Refractory Multiple Myeloma and Advanced Solid Tumors Participants With Normal Renal Function or Severe Renal Impairment
A Phase 1 study testing Ixazomib in people with Multiple Myeloma and Advanced Solid Tumors, run by Millennium Pharmaceuticals, Inc. at 11 sites in 2 countries.
Trial summary
The purpose of this study is to characterize the single-dose pharmacokinetic (PK) parameters of ixazomib (MLN9708) in cancer participants with either normal renal function or severe renal impairment (RI), including participants with end-stage renal disease (ESRD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Advanced Solid Tumors
- What is being tested?
- Ixazomib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 16 Sep 2013to 18 Nov 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants 18 years or older
- Participants with multiple myeloma (MM) diagnosed according to standard criteria or participants with a diagnosis of an advanced malignant solid tumor for which standard, curative, or life prolonging treatment does not exist or is no longer effective. Participants with multiple myeloma must have had at least 1 prior therapy
- A calculated creatinine clearance (CrCl) that meets entry criteria for enrollment (i.e., calculated CrCl either ≥ 90 mL/min for normal renal function or < 30 mL/min for severe renal impairment)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception through 90 days after the last dose of study drug or agree to practice true abstinence
- Male participants who agree to practice effective barrier contraception through 90 after the last dose of study drug or agree to practice true abstinence
- Voluntary written informed consent
- Suitable venous access
Who cannot join
- Female participants who are pregnant or lactating and breastfeeding
- Failure to have recovered from clinically significant effects of prior chemotherapy (defined as toxicity greater than Grade 1 with the exception of alopecia)
- Major surgery or radiotherapy within 14 days before study drug administration
- Dexamethasone (or equivalent systemic steroid) higher than physiologic dosing within 7 days before study drug administration
- Central nervous system involvement
- Infection requiring IV antibiotic therapy or other serious infection within 14 days prior to first dose of study drug
Show all 13Show fewer
- Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukemia, myeloproliferative syndrome, or primary amyloidosis (with the exception of patients in whom amyloidosis has been documented as a complication of MM, who will be evaluated on a case-by-case basis for trial participation)
- Systemic treatment with strong and moderate inhibitors of Cytochrome P1A2 (CYP1A2), strong and moderate inhibitors of Cytochrome P3A (CYP3A), or clinically significant CYP3A inducers or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study drug
- Evidence of uncontrolled cardiovascular conditions
- Ongoing or active infection, or known human immunodeficiency virus (HIV) positive
- Comorbid systemic illness or psychiatric illness that could interfere with study completion
- Known allergy to study medications
- Inability to swallow oral medication or condition that could interfere with oral absorption or tolerance of treatment
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States10 sites
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
University of Maryland
Baltimore, Maryland, 21201
Mary Crowley Cancer Research Centers Medical City
Dallas, Texas, 75201
University of Kansas Cancer Center, Clinical Research Center
Fairway, Kansas, 66205
Institute of Oncology Hematology Biomedical Research
Laredo, Texas, 78041
Sarah Cannon Cancer Center
Nashville, Tennessee, 37203
Mount Sinai Medical Center
New York, New York, 31406
University of Oklahoma Peggy and Charles Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
Illinois Cancer Care
Peoria, Illinois, 61615
University of Texas Health Science Center San Antonio
San Antonio, Texas, 78229
About this study
Official title: Phase 1/1b Pharmacokinetics Study of Oral MLN9708 in Patients With Relapsed/Refractory Multiple Myeloma and Advanced Solid Tumors With Normal Renal Function or Severe Renal Impairment
The purpose of this study is to characterize the single-dose pharmacokinetic (PK) parameters of ixazomib (MLN9708) in cancer participants with either normal renal function or severe renal impairment (RI), including participants with end-stage renal disease (ESRD).
Read the detailed description
The drug tested in this study was called ixazomib (MLN9708). Ixazomib was administered to participants with cancer and either normal renal function or severe renal impairment, including end-stage renal disease (ESRD) requiring hemodialysis. This study characterized the PK, safety and efficacy of ixazomib.
The study enrolled 41 participants (37 multiple myeloma and 4 advanced solid tumor). The study was conducted in 2 parts, Part A and Part B. Participants were enrolled to receive:
- Ixazomib 3.0 mg
In Part A, all participants were asked to take one 3 mg ixazomib capsule, orally on Day 1. Participants who tolerated ixazomib in Part A had the option of continuing the study by participating in Part B. In Part B, participants received ixazomib (4, 3, or 2.3 mg per protocol) on Days 1, 8, and 15 of each 28-day cycle until participants experienced disease progression or unacceptable toxicity.
This multicenter trial was conducted at 6 study sites in the United States and Canada. The overall time to participate in this study was 435 days. Participants made multiple scheduled visits to the clinic.
- Conditions
- Multiple Myeloma, Advanced Solid Tumors
- Being tested
- Ixazomib
- Keywords
- Drug Therapy
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IxazomibDrug
Also called MLN9708
Ixazomib capsules
| Study group | Role | What they receive |
|---|---|---|
| Normal Renal Function: Ixazomib | Experimental | In the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity. Receives: Drug: Ixazomib |
| Severe Renal Impairment: Ixazomib | Experimental | In the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity. Receives: Drug: Ixazomib |
| End-stage Renal Disease: Ixazomib | Experimental | In the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity. Receives: Drug: Ixazomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib
Measured: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Measured: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
Unbound AUClast: Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
Measured: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
Secondary outcomes (3)
Number of Participants With Adverse Events
Adverse Event 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 (eg, 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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Measured: From signing of first dose of study drug up to the 30 days after the last dose of study drug (approximately up to 885 days)
Percentage of Participants With Overall Response (OR) in Relapsed/Refractory Multiple Myeloma (RRMM) Participants
Overall response rate defined as percentage of relapsed/refractory multiple myeloma participants who achieved partial response (PR), complete response (CR) and very good partial response (VGPR) according to International Myeloma Working Group Criteria. PR=>50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >90% or <200 mg/24 h. If serum and urine M-protein are unmeasurable, >50% decrease in difference between involved and uninvolved free light chain levels in place of M-protein criteria. If serum and urine M-protein and serum free light assay are not measurable, >50% reduction in plasma cells in place of M-protein, provided baseline bone marrow plasma cell >0%; CR=negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow; VGPR=serum and urine M-protein detectable by immunofixation but not on electrophoresis or > 90% reduction in serum M-protein plus urine M-protein level <100 mg/24 h.
Measured: Day 1 of every other cycle from cycle 1 (each cycle of 28 days) up to progression of disease (approximately up to 855 days)
Duration of Response (DOR) in RRMM Participants
DOR was defined as time from date of first documentation of a PR or better to date of first documentation of progressive disease (PD) for responders. Increase of >25% from lowest response value in any one or more of following: Serum M-component and/or (absolute increase must be >0.5 g/dL); Urine M-component and/or (the absolute increase must be >200 mg/24 h); difference between involved and uninvolved free light chain (FLC) levels and the absolute increase must be > 10 mg/dL; Bone marrow plasma cell percentage; absolute percentage must be > 5%; Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas; Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Responders without PD were censored at the date of the last response assessment that was stable disease (SD) or better.
Measured: Day 1 of every other cycle from cycle 1 (each cycle of 28 days) up to progression of disease (approximately up to 855 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2013 (estimated)
- Study start16 Sep 2013
- Primary completion3 Mar 2015
- Study completion18 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Millennium Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Millennium Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01830816
- Sponsor's protocol ID
- C16015
- Other IDs
- U1111-1158-2763, 165055
- Status last verified
- Mar 2019
- First submitted
- 4 Apr 2013
- Last updated
- 10 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/1b Pharmacokinetics Study of Oral MLN9708 in Patients With Relapsed/Refractory Multiple Myeloma and Advanced Solid Tumors With Normal Renal Function or Severe Renal Impairment
- ClinicalTrials.gov ID
- NCT01830816
- Acronym / sponsor ID
- C16015
- Conditions
- Multiple Myeloma, Advanced Solid Tumors
- Keywords
- Drug Therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 16 Sep 2013 (actual)
- Primary completion
- 3 Mar 2015 (actual)
- Study completion
- 18 Nov 2016 (actual)
- First posted
- 12 Apr 2013 (estimated)
- Results
- Posted 10 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to characterize the single-dose pharmacokinetic (PK) parameters of ixazomib (MLN9708) in cancer participants with either normal renal function or severe renal impairment (RI), including participants with end-stage renal disease (ESRD).
Detailed description
The drug tested in this study was called ixazomib (MLN9708). Ixazomib was administered to participants with cancer and either normal renal function or severe renal impairment, including end-stage renal disease (ESRD) requiring hemodialysis. This study characterized the PK, safety and efficacy of ixazomib.
The study enrolled 41 participants (37 multiple myeloma and 4 advanced solid tumor). The study was conducted in 2 parts, Part A and Part B. Participants were enrolled to receive:
- Ixazomib 3.0 mg
In Part A, all participants were asked to take one 3 mg ixazomib capsule, orally on Day 1. Participants who tolerated ixazomib in Part A had the option of continuing the study by participating in Part B. In Part B, participants received ixazomib (4, 3, or 2.3 mg per protocol) on Days 1, 8, and 15 of each 28-day cycle until participants experienced disease progression or unacceptable toxicity.
This multicenter trial was conducted at 6 study sites in the United States and Canada. The overall time to participate in this study was 435 days. Participants made multiple scheduled visits to the clinic.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Normal Renal Function: Ixazomib | Experimental | Drug: IxazomibIn the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity. |
| Severe Renal Impairment: Ixazomib | Experimental | Drug: IxazomibIn the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity. |
| End-stage Renal Disease: Ixazomib | Experimental | Drug: IxazomibIn the 15 day period that constitutes Part A of the trial, participants received a single oral dose of ixazomib 3.0 mg capsules. Participants from Part A had the option of continuing the study by participating in Part B, where they received ixazomib (4, 3, or 2.3 mg per protocol) capsules, orally on Days 1, 8, and 15 of each 28-day cycle until disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female participants 18 years or older
- Participants with multiple myeloma (MM) diagnosed according to standard criteria or participants with a diagnosis of an advanced malignant solid tumor for which standard, curative, or life prolonging treatment does not exist or is no longer effective. Participants with multiple myeloma must have had at least 1 prior therapy
- A calculated creatinine clearance (CrCl) that meets entry criteria for enrollment (i.e., calculated CrCl either ≥ 90 mL/min for normal renal function or < 30 mL/min for severe renal impairment)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception through 90 days after the last dose of study drug or agree to practice true abstinence
Key exclusion criteria (13 listed)
- Female participants who are pregnant or lactating and breastfeeding
- Failure to have recovered from clinically significant effects of prior chemotherapy (defined as toxicity greater than Grade 1 with the exception of alopecia)
- Major surgery or radiotherapy within 14 days before study drug administration
- Dexamethasone (or equivalent systemic steroid) higher than physiologic dosing within 7 days before study drug administration
- Central nervous system involvement
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IxazomibAlso: MLN9708Ixazomib capsules | Drug | End-stage Renal Disease: Ixazomib, Normal Renal Function: Ixazomib, Severe Renal Impairment: Ixazomib |
Primary outcome
Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib
Time frame: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Time frame: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
Unbound AUClast: Unbound Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
Time frame: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose
3 secondary outcomes
Number of Participants With Adverse Events
Time frame: From signing of first dose of study drug up to the 30 days after the last dose of study drug (approximately up to 885 days)
Percentage of Participants With Overall Response (OR) in Relapsed/Refractory Multiple Myeloma (RRMM) Participants
Time frame: Day 1 of every other cycle from cycle 1 (each cycle of 28 days) up to progression of disease (approximately up to 855 days)
Duration of Response (DOR) in RRMM Participants
Time frame: Day 1 of every other cycle from cycle 1 (each cycle of 28 days) up to progression of disease (approximately up to 855 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Millennium Pharmaceuticals, Inc.
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ixazomib in people with Multiple Myeloma and Advanced Solid Tumors, run by Millennium Pharmaceuticals, Inc. at 11 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Unbound Cmax: Unbound Maximum Observed Plasma Concentration for Ixazomib (time frame: Part A, Day 1: Predose and at multiple timepoints (up to 336 hours) post-dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2019.