Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Ixazomib

Proteasome Inhibitors

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

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.

IXAZOMIB

Medical Monitor

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.

A Study of IXAZOMIB in Adult Patients With Lymphoma

An Open-Label, Dose-Escalation, Phase 1 Study of IXAZOMIB (MLN9708), A Second-Generation Proteasome Inhibitor, in Adult Patients With Lymphoma

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.

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.

Vital signs included body temperature, weight, systolic and diastolic blood pressure and heart rate.

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.

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 is the plasma drug concentration at time zero following bolus intravenous injection, obtained from the plasma concentration-time curve.

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) is the time required for half of the drug to be eliminated from the plasma.

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) is the total amount of drug excreted in the 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.

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 is the maximum inhibition of 20S proteasome activity in whole blood.

TEmax: Time to reach the maximum observed effect (Emax), equal to time (hours) to Emax.

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.

Millennium Pharmaceuticals, Inc.

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Ixazomib (MLN9708) 0.125 mg/m\^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity.

Ixazomib 0.125 mg/m^2

Ixazomib (MLN9708) 0.25 mg/m\^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity.

Ixazomib 0.25 mg/m^2

Ixazomib (MLN9708) 0.5 mg/m\^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity.

Ixazomib 0.5 mg/m^2

Ixazomib (MLN9708) 1.0 mg/m\^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity.

Ixazomib 1.0 mg/m^2

Ixazomib (MLN9708)1.4 mg/m\^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity.

Ixazomib 1.4 mg/m^2

Ixazomib (MLN9708) 1.76 mg/m\^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity.

Ixazomib 1.76 mg/m^2

Ixazomib (MLN9708) 2.34 mg/m\^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity.

Ixazomib 2.34 mg/m^2

Ixazomib (MLN9708) 3.11 mg/m\^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity.

Ixazomib 3.11 mg/m^2

Total

Age, Continuous

Sex: Female, Male

White

Black or African American

Other

Missing

Race/Ethnicity, Customized

Hispanic or Latino

Not Hispanic or Latino

Canada

United States

Region of Enrollment

Body surface area (BSA)

Height

Weight

ECOG performance status is used to assess how the disease affects the daily living abilities of the participant. It ranges on the scale from 0-5 (0= normal activity; 1= symptoms but ambulatory; 2= in bed for less than (\<) 50 percent (%) of the time; 3= in bed for greater than (\>) 50% of the time; 4= 100% bedridden; 5= dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status

Unknown

Not Applicable

Ann Arbor staging is staging system for lymphomas. The stage is determined by location of tumor. Stage I (located in a single region, usually 1 lymph node and surrounding area), Stage II (located in 2 separate regions, an affected lymph node or organ and a second affected area, and both affected areas are confined to 1 side of diaphragm), Stage III (spread to both sides of diaphragm, including organ/area near lymph nodes/spleen), Stage IV (diffuse or disseminated involvement of 1 or more extra lymphatic organs, including any involvement of liver, bone marrow or nodular involvement of lungs).

Ann Arbor Stage

Follicular lymphoma

Diffused large B-cell lymphoma

Peripheral T-cell lymphoma not otherwise specified

Hodgkin's lymphoma

Others

Cutaneous T-cell lymphoma

For this outcome measure, number of participants evaluable were 1, 1, 1, 1, 4, 7, 9 and 4 for each arm, respectively.

Disease Histological Class

Time Since Primary Diagnosis to First Dose

Safety population included all participants who received at least 1 dose of ixazomib.

Medical Director

Adverse Events

Serious Adverse Events

Ixazomib1.76 mg/m^2

Ixazomib 3.11 mg/m²

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Blood and lymphatic system disorders

Metabolism and nutrition disorders

Investigations

Number of Participants Reporting at Least 1 TEAE Related to Laboratory Assessments

Number of Participants With Clinically Significant Change From Baseline in Vital Signs

All participants who received ixazomib (MLN9708) 0.125 mg/m\^2, 0.25 mg/m\^2, 0.5 mg/m\^2, 1.0 mg/m\^2, 1.4 mg/m\^2, 1.76 mg/m\^2, 2.34 mg/m\^2 or 3.11 mg/m\^2 in dose-escalation cohorts .

All Participants

DLT-Evaluable Population included participants who received all Cycle 1 doses of MLN9708 and who completed Cycle 1. If Cycle 1 was interrupted by a DLT, the participant was included in this population.

Maximum Tolerated Dose (MTD)

All participants who received MLN9708 at dose 0.125 mg/m\^2, 0.25 mg/m\^2, 0.5 mg/m\^2, 1.0 mg/m\^2, 1.4 mg/m\^2, 1.76 mg/m\^2, 2.34 mg/m\^2 and 3.11 mg/m\^2 in Phase 1.

Recommended Phase 2 Dose (RP2D)

Day 1 (n= 1, 1, 1, 0, 4, 7, 10, 5)

Day 15 (n= 0, 0, 1, 1, 4, 3, 7, 2)

The pharmacokinetic (PK) analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters where Days 1 and 15 assessments were available.

C0: Initial Plasma Concentration After Bolus Intravenous Administration

Day 1 (n= 0, 0, 0, 0, 4, 6, 7, 5)

Day 15 (n= 0, 0, 1, 1, 4, 0, 7, 2)

The PK analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters where Days 1 and 15 assessments were available. AUC(0-168) is not reported for ixazomib 0.125 and 0.25 mg/m\^2 as the participants were not evaluable for this parameter.

AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib

The PK analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters.T1/2 is not reported for ixazomib 0.125 and 0.25 mg/m\^2 as the participants were not evaluable for this parameter.

Terminal Phase Elimination Half-life (T1/2) for Ixazomib

The PK analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters. Rac is reported for ixazomib 1.4, 2.34 and 3.11 mg/m\^2 groups only as it could not be estimated for the other dosing groups.

Rac: Accumulation Ratio for Ixazomib

Day 1 (n= 1, 1, 1, 0, 4, 6, 8, 5)

Day 15 (n= 0, 1, 1, 1, 4, 3, 7, 2)

Ixazomib (MLN9708) 0.125 mg/m\^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity..

The PK analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters where Days 1 and 15 assessments were available.

Ae (0-4): Amount of Drug Excreted in Urine From 0 to 4 Hours Postdose

The PK analysis population was defined as participants who had sufficient dosing data and ixazomib concentration-time data to permit the calculation of PK parameters where Days 1 and 15 assessments were available.

Fe (0-4): Fraction of Dose Excreted Unchanged in Urine From 0 to 4 Hours Postdose

Day 1 (n= 0, 0,1, 0, 4, 6, 8, 5)

Day 15 (n= 0, 0, 1, 1, 4, 3, 6, 2)

The PK analysis population included all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of PK parameters where Days 1 and 15 assessments were available. CLr is not reported for ixazomib 0.125 and 0.25 mg/m\^2 as the participants were not evaluable for this parameter.

CLr: Renal Clearance

Day 1 (n= 1, 1, 1, 1, 3, 7, 5, 4)

Day 15 (n= 0, 1, 1, 1, 3, 3, 4, 2)

The pharmacodynamic analysis population included participants who had sufficient dosing data and effect-time data to permit calculation of pharmacodynamic parameters where Days 1 and 15 assessments were available.

Emax: Maximum Observed Effect for Ixazomib

TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib

Response-evaluable population included participants who received at least 1 dose of study drug, had measurable disease at baseline, and at least 1 postbaseline disease assessment for analyses of response.

Overall Best Response

Ixazomib (MLN9708) 0.125 mg/m\^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until progressive disease (PD) or unacceptable toxicity.

Ixazomib (MLN9708) 1.4 mg/m\^2, injection, intravenously, once weekly on Days 1, 8, and 15 in 28-day treatment cycles until PD or unacceptable toxicity.

Spots Global Cancer Trial Database for A Study of IXAZOMIB in Adult Patients With Lymphoma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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