LymphomaPhase 1NCT00893464
A Study of IXAZOMIB in Adult Patients With Lymphoma
A Phase 1 study testing IXAZOMIB in people with Lymphoma, run by Millennium Pharmaceuticals, Inc. at 7 sites in 2 countries.
Trial summary
This study is an open-label, multicenter, phase 1, dose-escalation study of IXAZOMIB in adult patients with lymphoma. This study will be the first to administer IXAZOMIB to patients with lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- IXAZOMIB
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Aug 2009to Oct 2014
- 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 patients 18 years or older.
- Eastern Cooperative Oncology Group performance status 0-2.
- Patients must have a confirmed diagnosis of lymphoma that is relapsed and/or refractory after at least 2 prior chemotherapeutic regimens and for which no curative option exists. Patients with Waldenstrom's macroglobulinemia are not eligible for enrollment in this study. Patients with Hodgkin lymphoma are considered eligible for this study.
- Suitable venous access for PK and pharmacodynamic evaluations.
- Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
- Male patients who agree to to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
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- Voluntary written consent must be obtained.
- Adequate blood and chemistry values during the screening period:
- Absolute neutrophil count (ANC) ≥ 1,500/mm3; platelet count ≥ 100,000/mm3.
- Total bilirubin must be ≤ 1.5 × the upper limit of the normal range upper limit of normal (ULN).
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be ≤ 2.5 × the upper limit of normal (ULN). AST and ALT may be elevated up to 5 times the upper limit of normal if their elevation can be reasonably ascribed to the presence of metastatic disease.
- Calculated creatinine clearance ≥ 30 mL/minute.
Who cannot join
- Peripheral neuropathy ≥ Grade 2.
- Female patients who are lactating or have a positive serum pregnancy test during the screening period .
- Major surgery within 14 days before the first dose of treatment.
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment.
- Life-threatening illness unrelated to cancer.
- Diarrhea > Grade 1 based on the NCI CTCAE categorization.
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- Systemic antineoplastic therapy/or radiotherapy within 21 days before the first dose of study treatment.
- Systemic treatment with prohibited medications.
- Patient has symptomatic brain metastases.
- Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or myocardial infarction within the past 6 months.
- QTc > 470 milliseconds (msec) on a 12-lead electrocardiogram (ECG) obtained during the screening period.
- Known human immunodeficiency virus (HIV), hepatitis B or hepatitis C 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.
- Treatment with any investigational products within 28 days before the first dose of study treatment.
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
Tower Cancer Research Center
Beverly Hills, California, 90211
Rocky Mountain Cancer Center
Denver, Colorado, 80218
University of Wisconsin Madison
Madison, Wisconsin, 53792
Cornell University
New York, New York, 10021
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Kansas University Medical Center
Westwood, Kansas, 66160
About this study
Official title: An Open-Label, Dose-Escalation, Phase 1 Study of IXAZOMIB (MLN9708), A Second-Generation Proteasome Inhibitor, in Adult Patients With Lymphoma
This study is an open-label, multicenter, phase 1, dose-escalation study of IXAZOMIB in adult patients with lymphoma. This study will be the first to administer IXAZOMIB to patients with lymphoma.
- Conditions
- Lymphoma
- Being tested
- IXAZOMIB
- Medical subject headings
- Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IXAZOMIBDrug
Patients will be administered IXAZOMIB by IV on Days 1, 8, and 15 of a 28-day cycle. The first stage of the study will be initiated at a starting dose of 0.125 mg/m2. Subsequent doses will increase until a maximum tolerated dose (MTD) is established.
| Study group | Role | What they receive |
|---|---|---|
| IXAZOMIB | Experimental | Not described Receives: Drug: IXAZOMIB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An Adverse Event (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 (example, 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. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.
Measured: Baseline up to 30 days after last dose of study drug
Number of Participants Reporting at Least 1 TEAE Related to Laboratory Assessments
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Hematology, clinical chemistry and urinalysis were performed. TEAEs related to laboratory assessment observed at any time-points were reported under 3 system organ classes: blood and lymphatic system disorders, metabolism and nutrition disorders, and investigations.
Measured: Baseline and Days 1, 8, and 15 of each treatment cycle (up to Cycle 45)
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Vital signs included body temperature, weight, systolic and diastolic blood pressure and heart rate.
Measured: Baseline and Days 1, 8, 15 of each treatment cycle up to 45 treatment cycles
Maximum Tolerated Dose (MTD)
The MTD was defined as the highest dose of ixazomib that generated dose limiting toxicity (DLT) during Cycle 1 in 0 of 3 or 1 of 6 participants. DLT defined as any of the following considered possibly related to therapy by investigator: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cell per cubic millimeter [cells/mm^3]) for >7 days; Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia for >7 days; platelet count <25,000 cells/mm^3; Grade 3 thrombocytopenia with clinically significant bleeding; platelet count <10,000/mm^3; Grade 2 peripheral neuropathy with pain or Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by maximal supportive therapy; Grade 3 QTc prolongation>500 millisecond (msec);any >=Grade 3 nonhematologic toxicity except arthralgia/myalgia; <1 week fatigue; delay in the initiation of the subsequent therapy cycle by >=7 days ; other Grade 2 ixazomib-related nonhematologic toxicities requiring therapy discontinuation.
Measured: Treatment Cycle 1
Recommended Phase 2 Dose (RP2D)
The RP2D of Ixazomib was determined in Part 1 (dose escalation) on the basis of the totality of safety, tolerability, pharmacokinetics (PK), pharmacodynamic and preliminary efficacy data observed in Cycles 1 and 2 and beyond.
Measured: Baseline up to Treatment Cycle 45
Secondary outcomes (10)
C0: Initial Plasma Concentration After Bolus Intravenous Administration
C0 is the plasma drug concentration at time zero following bolus intravenous injection, obtained from the plasma concentration-time curve.
Measured: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 336 hours postdose)
AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib
AUC(0-168) is a measure of the area under the plasma concentration time-curve from time 0 to 168 hours postdose
Measured: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
Terminal Phase Elimination Half-life (T1/2) for Ixazomib
Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Measured: Cycle 1 Day 15: Predose and at multiple time points (up to 336 hours postdose)
Rac: Accumulation Ratio for Ixazomib
Rac was estimated as the ratio of AUC (0-168) on Day 15 and AUC (0-168) on Day 1. AUC (0-168) is the area under the plasma concentration-time curve from time 0 to 168 hours postdose.
Measured: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
Ae (0-4): Amount of Drug Excreted in Urine From 0 to 4 Hours Postdose
Ae (0-4) is the total amount of drug excreted in the urine from 0 to 4 hours postdose.
Measured: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
Fe (0-4): Fraction of Dose Excreted Unchanged in Urine From 0 to 4 Hours Postdose
Fe (0-4) is the fraction of the dose excreted unchanged in the urine from 0 to 4 hours postdose, calculated as percentage of the exact dose administered.
Measured: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
CLr: Renal Clearance
CLr is the volume of plasma from which the drug is completely removed by the kidney in a given amount of time, calculated as the amount of drug excreted in the urine divided by the area under the plasma concentration-time curve, expressed in liter per hour (L/hr).
Measured: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
Emax: Maximum Observed Effect for Ixazomib
Emax is the maximum inhibition of 20S proteasome activity in whole blood.
Measured: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib
TEmax: Time to reach the maximum observed effect (Emax), equal to time (hours) to Emax.
Measured: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
Overall Best Response
Overall best response is the best response observed for a participant during the study based on International Working Group (IWG) Response Criteria for malignant lymphoma. Complete response (CR) as per IWG is complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial response (PR) is a minimum of 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses and no increase in the size of other nodes. Stable disease (SD) is when a participant fails to attain the criteria needed for a CR or PR, but does not fulfill those for PD. PD is any new lesion or increase by >50% of previously involved sites from nadir.
Measured: Baseline up to Cycle 45
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2009 (estimated)
- Study startAug 2009
- Primary completionOct 2014
- Study completionOct 2014
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 LymphomaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 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
- NCT00893464
- Sponsor's protocol ID
- C16002
- Other IDs
- U1111-1166-8981
- Status last verified
- Oct 2015
- First submitted
- 4 May 2009
- Last updated
- 11 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Dose-Escalation, Phase 1 Study of IXAZOMIB (MLN9708), A Second-Generation Proteasome Inhibitor, in Adult Patients With Lymphoma
- ClinicalTrials.gov ID
- NCT00893464
- Acronym / sponsor ID
- C16002
- Conditions
- Lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Millennium Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2009
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 6 May 2009 (estimated)
- Results
- Posted 11 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an open-label, multicenter, phase 1, dose-escalation study of IXAZOMIB in adult patients with lymphoma. This study will be the first to administer IXAZOMIB to patients with lymphoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IXAZOMIB | Experimental | Drug: IXAZOMIB |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Male or female patients 18 years or older.
- Eastern Cooperative Oncology Group performance status 0-2.
- Patients must have a confirmed diagnosis of lymphoma that is relapsed and/or refractory after at least 2 prior chemotherapeutic regimens and for which no curative option exists. Patients with Waldenstrom's macroglobulinemia are not eligible for enrollment in this study. Patients with Hodgkin lymphoma are considered eligible for this study.
- Suitable venous access for PK and pharmacodynamic evaluations.
- Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
Key exclusion criteria (14 listed)
- Peripheral neuropathy ≥ Grade 2.
- Female patients who are lactating or have a positive serum pregnancy test during the screening period .
- Major surgery within 14 days before the first dose of treatment.
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment.
- Life-threatening illness unrelated to cancer.
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 |
|---|---|---|
| IXAZOMIBPatients will be administered IXAZOMIB by IV on Days 1, 8, and 15 of a 28-day cycle. The first stage of the study will be initiated at a starting dose of 0.125 mg/m2. Subsequent doses will increase until a maximum tolerated dose (MTD) is established. | Drug | IXAZOMIB |
Primary outcome
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to 30 days after last dose of study drug
An Adverse Event (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 (example, 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. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event.
Number of Participants Reporting at Least 1 TEAE Related to Laboratory Assessments
Time frame: Baseline and Days 1, 8, and 15 of each treatment cycle (up to Cycle 45)
The number of participants with any markedly abnormal standard safety laboratory values collected throughout study. Hematology, clinical chemistry and urinalysis were performed. TEAEs related to laboratory assessment observed at any time-points were reported under 3 system organ classes: blood and lymphatic system disorders, metabolism and nutrition disorders, and investigations.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time frame: Baseline and Days 1, 8, 15 of each treatment cycle up to 45 treatment cycles
Vital signs included body temperature, weight, systolic and diastolic blood pressure and heart rate.
Maximum Tolerated Dose (MTD)
Time frame: Treatment Cycle 1
The MTD was defined as the highest dose of ixazomib that generated dose limiting toxicity (DLT) during Cycle 1 in 0 of 3 or 1 of 6 participants. DLT defined as any of the following considered possibly related to therapy by investigator: Grade 4 neutropenia (absolute neutrophil count [ANC] <500 cell per cubic millimeter [cells/mm^3]) for >7 days; Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia for >7 days; platelet count <25,000 cells/mm^3; Grade 3 thrombocytopenia with clinically significant bleeding; platelet count <10,000/mm^3; Grade 2 peripheral neuropathy with pain or Grade 3 peripheral neuropathy; >=Grade 3 nausea/emesis, diarrhea controlled by maximal supportive therapy; Grade 3 QTc prolongation>500 millisecond (msec);any >=Grade 3 nonhematologic toxicity except arthralgia/myalgia; <1 week fatigue; delay in the initiation of the subsequent therapy cycle by >=7 days ; other Grade 2 ixazomib-related nonhematologic toxicities requiring therapy discontinuation.
Recommended Phase 2 Dose (RP2D)
Time frame: Baseline up to Treatment Cycle 45
The RP2D of Ixazomib was determined in Part 1 (dose escalation) on the basis of the totality of safety, tolerability, pharmacokinetics (PK), pharmacodynamic and preliminary efficacy data observed in Cycles 1 and 2 and beyond.
10 secondary outcomes
C0: Initial Plasma Concentration After Bolus Intravenous Administration
Time frame: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 336 hours postdose)
AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib
Time frame: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
Terminal Phase Elimination Half-life (T1/2) for Ixazomib
Time frame: Cycle 1 Day 15: Predose and at multiple time points (up to 336 hours postdose)
Rac: Accumulation Ratio for Ixazomib
Time frame: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
Ae (0-4): Amount of Drug Excreted in Urine From 0 to 4 Hours Postdose
Time frame: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
Fe (0-4): Fraction of Dose Excreted Unchanged in Urine From 0 to 4 Hours Postdose
Time frame: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
CLr: Renal Clearance
Time frame: Cycle 1, Days 1 and 15: 0 to 4 hours postdose
Emax: Maximum Observed Effect for Ixazomib
Time frame: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib
Time frame: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose)
Overall Best Response
Time frame: Baseline up to Cycle 45
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2015.
- 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.
7 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 Lymphoma, run by Millennium Pharmaceuticals, Inc. at 7 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 12 inclusion and 14 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 11 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 11 Nov 2015). 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?
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: Baseline up to 30 days after last dose of study drug). The study lists 5 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 11 Nov 2015.