A Study of IXAZOMIB in Adult Patients With Lymphoma
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|ClinicalTrials.gov Identifier: NCT00893464|
Recruitment Status : Completed
First Posted : May 6, 2009
Results First Posted : November 11, 2015
Last Update Posted : November 11, 2015
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma||Drug: IXAZOMIB||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-Label, Dose-Escalation, Phase 1 Study of IXAZOMIB (MLN9708), A Second-Generation Proteasome Inhibitor, in Adult Patients With Lymphoma|
|Study Start Date :||August 2009|
|Actual Primary Completion Date :||October 2014|
|Actual Study Completion Date :||October 2014|
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.
- 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.
- 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) ]C0 is the plasma drug concentration at time zero following bolus intravenous injection, obtained from the plasma concentration-time curve.
- 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) ]AUC(0-168) is a measure of the area under the plasma concentration time-curve from time 0 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) ]Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
- Rac: Accumulation Ratio for Ixazomib [ Time Frame: Cycle 1 Days 1 and 15: Predose and at multiple time points (up to 168 hours postdose) ]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.
- 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 ]Ae (0-4) is the total amount of drug excreted in the urine from 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 ]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.
- CLr: Renal Clearance [ Time Frame: Cycle 1, Days 1 and 15: 0 to 4 hours postdose ]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).
- 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) ]Emax is the maximum inhibition of 20S proteasome activity in whole blood.
- 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) ]TEmax: Time to reach the maximum observed effect (Emax), equal to time (hours) to Emax.
- Overall Best Response [ Time Frame: Baseline up to Cycle 45 ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00893464
|United States, California|
|Tower Cancer Research Center|
|Beverly Hills, California, United States, 90211|
|United States, Colorado|
|Rocky Mountain Cancer Center|
|Denver, Colorado, United States, 80218|
|United States, Kansas|
|Kansas University Medical Center|
|Westwood, Kansas, United States, 66160|
|United States, New York|
|New York City, New York, United States, 10021|
|United States, Pennsylvania|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|United States, Wisconsin|
|University of Wisconsin Madison|
|Madison, Wisconsin, United States, 53792|
|Jewish General Hospital|
|Montreal, Quebec, Canada, H3T 1E2|
|Study Director:||Medical Monitor||Millennium Pharmaceuticals, Inc.|