Phase 2 Study of Oral IXAZOMIB in Adult Participants With... | NCT01939899

ID	Type	Description
2013-002302-32	EudraCT Number
U1111-1164-7551	Other Identifier	WHO
166547	Registry Identifier	HC-CTD
REec-2016-2137	Registry Identifier	REec
13/EM/0373	Registry Identifier	NRES

Label	Type	Description	Intervention Names
IXAZOMIB	Experimental	Ixazomib 4, 5.3 and 7 milligram (mg), orally, once on Days 1, 8 and 15 in a 28 day treatment cycle followed by a rest period of 13 days, for up to Cycle 29 or until disease progression or unacceptable toxicity at lead-in phase for participants with NHL. After completion of lead-in phase, participants will continue into Phase 2. Participants in Phase 2 will receive Ixazomib at RP2D dose, orally, once weekly on Days 1, 8 and 15 in a 28 day treatment cycle followed by a rest period of 13 days , for up to Cycle 29 or until disease progression or unacceptable toxicity in Phase 2 for participants with RRFL.	Drug: IXAZOMIB

Name	Type	Description	Arm Group Labels	Other Names
IXAZOMIB	Drug	Each 28-day treatment cycle will include oral administration of IXAZOMIB on Days 1, 8, and 15 followed by a rest period of 13 days.	IXAZOMIB

Measure	Description	Time Frame
Number of Participants With Overall Response Rate (ORR)	ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator using the international Working Group criteria for participants CR: disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.	Baseline up to Day 15 Cycle 29 (approximately up to Day 802) or until PD or the start of alternate therapies

Measure	Description	Time Frame
Lead-in Dose Finding Phase: Recommended Phase 2 Dose (RP2D)		Baseline up to Cycle 1 Day 28
Progression Free Survival (PFS)	PFS is defined as the time from the date of first dose of study treatment to the date of first documented PD or death. Participants without documentation of PD will be censored at the date of last response assessment that is SD or better. Participants without response assessment will be censored at the date of first dose.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female participants 18 years or older.
Participants must have a pathologically confirmed diagnosis of non-Hodgkin lymphoma (NHL) (for the lead-in dose-finding phase) and FL (for phase 2).
Participants must have radiographically or clinically measurable disease.
Participants must be relapsed and/or refractory after at least 1 prior therapy (excluding radiation) with documented progressive disease at the time of enrollment.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence.
Male participants who agree to practice effective barrier contraception or agree to practice true abstinence.
Voluntary written consent.
Suitable venous access.
Appropriate clinical laboratory values as defined in the protocol.
Recovered from toxicities of prior anticancer therapy.
If the trial proceeds to the second step on the basis of the tandem 2-step design, participants must be confirmed PSMB1 positive at the central laboratory before treatment.

Exclusion Criteria

Peripheral neuropathy that is greater or equal to Grade 2 or Grade 1 with pain.
Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
Autologous stem cell transplant within 6 months before Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time.
Major surgery within 14 days before the first dose of study drug.
Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
Comorbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the participants inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
Evidence of current uncontrolled cardiovascular conditions including uncontrolled hypertension, severe uncontrolled ventricular arrhythmias, unstable angina, New York Heart Association (NYHA) Class III or IV cardiac disease, or myocardial infarction within the past 6 months.
Diarrhea greater than (>) Grade 1 on the basis of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) categorization.
Systemic antineoplastic (including glucocorticoids > the equivalent of 15 mg of prednisone daily), experimental, or radiation therapy within 21 days before the first dose of study drug.
Prior treatment with rituximab or other unconjugated antibody treatment within 42 days (21 days if clear evidence of progressive disease or immediate treatment is mandated).
Treatment with radioimmunoconjugates or toxin immunoconjugates within 12 weeks before the first dosing of study treatment.
Systemic treatment with strong inhibitors of Cytochrome P450 1A2 (CYP1A2) or Cytochrome P450 3A (CYP3A), or strong CYP3A inducers within 14 days before the first dose of IXAZOMIB - Ongoing systemic therapy with corticosteroids.
Central nervous system (CNS) involvement that is clinically uncontrolled or newly diagnosed in the last 4 months.
Ongoing or active systemic viral infection, known human immunodeficiency virus (HIV) positive, known active hepatitis B virus or known active hepatitis C virus.
Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ.
Platelet transfusions within 3 days before the 1st dose of study drug.
Inability to swallow capsules, or inability or unwillingness to avoid taking anything by mouth except for water and prescribed medication for 2 hours before and 1 hour after dose of IXAZOMIB - Known allergy to boron or excipients in the formulation.

Name	Affiliation	Role
Medical Director	Millennium Pharmaceuticals, Inc.	Study Director

ID	Title	Description
FG000	Lead-in Dose Finding Phase: Ixazomib 4 mg	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.
FG001

Arm/Group Information

ID	Title	Description
BG000	Lead-in Dose Finding Phase: Ixazomib 4 mg	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.
BG001	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
BG002	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
BG003	Phase 2: PSMB1 Positive	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.
BG004	Phase 2: PSMB1 Negative	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.
BG005	Total	Total of all reporting groups

Units	Counts
Participants	BG0003 BG0017 BG0026 BG00312 BG0041 BG00529

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00072.0± 6.56 BG00157.9± 11.13 BG00264.3± 7.71 BG003

Sex: Female, Male

The safety population included all enrolled participants who had received at least 1 dose of ixazomib.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0001 BG0011 BG002

Race (NIH/OMB)

The safety population included all enrolled participants who had received at least 1 dose of ixazomib.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010

Region of Enrollment

The safety population included all enrolled participants who had received at least 1 dose of ixazomib.

Number

participants

Title

Denominators

Categories

Belgium

Title	Measurements
	BG0001 BG0012 BG002

Smoking classification

The safety population included all enrolled participants who have received at least 1 dose of ixazomib.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Never smoked	BG0002 BG0014 BG002

Height

The safety population included all enrolled participants who have received at least 1 dose of ixazomib.

Mean

Standard Deviation

centimeter (cm)

Title

Denominators

Categories

Title	Measurements
	BG000170.0± 7.04 BG001175.0± 11.50

Weight

The safety population included all enrolled participants who have received at least 1 dose of ixazomib.

Mean

Standard Deviation

kilogram (kg)

Title

Denominators

Categories

Title	Measurements
	BG00076.1± 11.27 BG00185.8± 20.72

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Overall Response Rate (ORR)

ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the investigator using the international Working Group criteria for participants CR: disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.

The response-evaluable population included all participants who received at least 1 dose of ixazomib, had measurable disease at baseline, and had at least 1 post baseline disease assessment.

Posted

Number

participants

Baseline up to Day 15 Cycle 29 (approximately up to Day 802) or until PD or the start of alternate therapies

ID	Title	Description
OG000	Lead-in Dose Finding Phase: Ixazomib 4 mg	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.
OG001	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
OG002	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
OG003	Phase 2: PSMB1 Positive	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.
OG004	Phase 2: PSMB1 Negative	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.

Units	Counts
Participants	OG0003 OG0015 OG0025 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Secondary

Lead-in Dose Finding Phase: Recommended Phase 2 Dose (RP2D)

The dose limiting toxicity (DLT)- evaluable population included all participants who received all Cycle 1 doses of ixazomib and had completed Cycle 1 safety procedures, or experience a DLT in Cycle 1 in the lead-in dose finding phase of the study.

Posted

Number

Baseline up to Cycle 1 Day 28

ID	Title	Description
OG000	Lead-in Dose Finding Phase: All Participants	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.

Units	Counts
Participants	OG000

Secondary

Progression Free Survival (PFS)

PFS is defined as the time from the date of first dose of study treatment to the date of first documented PD or death. Participants without documentation of PD will be censored at the date of last response assessment that is SD or better. Participants without response assessment will be censored at the date of first dose.

The modified intent-to-treat (mITT) population included all participants who received at least 1 dose of ixazomib in the phase 2 portion of the study or who received at least 1 dose of ixazomib and are treated at the RP2D in the lead-in dose finding phase of the study.

Posted

Median

95% Confidence Interval

months

Time from the date of first dose of study treatment to the date of first documented PD or death (approximately up to Day 802)

ID	Title	Description
OG000	Lead-in Dose Finding: Ixazomib 5.3 mg (RP2D)	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
OG001	Phase 2: PSMB1 Positive	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.

Secondary

Phase 2: Rate of Disease Control

Rate of disease control is defined as percentage of participants who achieved a SD or better for greater than or equal to (>=) 6 months.

The response-evaluable population included all participants who received at least 1 dose of ixazomib, had measurable disease at baseline, and had at least 1 post baseline disease assessment.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline or until occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 805)

ID	Title	Description
OG000	Phase 2: PSMB1 Positive	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.
OG001	Phase 2: PSMB1 Negative	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.

Units

Secondary

Time to Response (TTR)

TTR is defined as the time from the date of first dose of study treatment to the date of the first documentation of a PR or better response in a participant who responded.

The response-evaluable population included all participants who received at least 1 dose of ixazomib, had measurable disease at baseline, and had at least 1 post baseline disease assessment. Participants who were evaluable for this given measure at a given time point were included for this assessment.

Posted

Median

95% Confidence Interval

days

Time from the date of first dose of study treatment to the date of first documented PR or better response or death (approximately up to Day 802)

ID	Title	Description
OG000	Lead-in Dose Finding Phase: Ixazomib 4 mg	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.
OG001	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
OG002

Secondary

Duration of Response (DOR)

The DOR is defined as the time from the date of first documentation of a response to the date of first documented PD. Responders without documentation of PD will be censored at the date of last response assessment. DOR was categorized as CR+PR and CR.

Posted

Median

95% Confidence Interval

months

Time from the date of first documentation of a response to the date of first documented PD (approximately up to Day 802)

ID	Title	Description
OG000	Lead-in Dose Finding Phase: Ixazomib 4 mg	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.
OG001	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.

Secondary

Phase 2: Number of Participants With Response Rates in PSMB1 Positive and PSMB1 Negative

The biomarker population included all participants positive or negative for the PSMB1 biomarker and where the assay has passed quality control. Data will be derived from a baseline blood sample.

Posted

Number

participants

Baseline up to occurrence of disease progression, unacceptable toxicities, or discontinuation of study due to any other reasons (approximately up to Day 802)

ID	Title	Description
OG000	Phase 2: PSMB1 Positive	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.
OG001	Phase 2: PSMB1 Negative	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.

Units	Counts
Participants

Secondary

Number of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

The safety population included all enrolled participants who had received at least 1 dose of ixazomib.

Posted

Number

participants

Baseline up to 30 days after last dose of study drug (approximately up to Day 832)

ID	Title	Description
OG000	Lead-in Dose Finding Phase: Ixazomib 4 mg	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.
OG001	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
OG002	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.

Secondary

Lead-in Dose Finding Phase: Cmax: Maximum Observed Plasma Concentration for Ixazomib

The plasma pharmacokinetic (PK) analysis population included all participants enrolled in the lead-in dose finding phase that had sufficient dosing data and ixazomib concentration-time data. The PK analysis population where data at specified time points was available.

Posted

Mean

Standard Deviation

nanogram per milliliter (ng/mL)

Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose

ID	Title	Description
OG000	Lead-in Dose Finding Phase: Ixazomib 4 mg	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.
OG001	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
OG002	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.

Secondary

Lead-in Dose Finding Phase: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib

The PK analysis population included all participants enrolled in the lead-in dose finding phase that had sufficient dosing data and ixazomib concentration-time data. The PK analysis population where data at specified time points was available.

Posted

Median

Full Range

hour

Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose

ID	Title	Description
OG000	Lead-in Dose Finding Phase: Ixazomib 4 mg	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.
OG001	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
OG002	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.

Secondary

Lead-in Dose Finding Phase: AUC(0-168): Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Postdose for Ixazomib

The PK analysis set where Cycle 1 Day 1 and 15 assessment were available. The PK analysis population included all participants enrolled in the lead-in dose finding phase that had sufficient dosing data and ixazomib concentration-time data. The PK analysis population where data at specified time points was available.

Posted

Mean

Standard Deviation

hour*nanogram per milliliter (h*ng/mL)

Cycle 1, Days 1 and 15 pre-dose and at multiple time points (up to 168 hours) post-dose

ID	Title	Description
OG000	Lead-in Dose Finding Phase: Ixazomib 4 mg	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.
OG001	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.
OG002	Lead-in Dose Finding Phase: Ixazomib 7.0 mg

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lead-in Dose Finding Phase: Ixazomib 4 mg	Ixazomib 4 milligram (mg), solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or progressive disease (PD) or the start of alternate therapies during lead-in dose finding in non-hodgkin lymphoma (NHL) participants.	0	3	1	3	3	3
EG001	Lead-in Dose Finding Phase: Ixazomib 5.3 mg	Ixazomib 5.3 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	3	7	3	7	7	7
EG002	Lead-in Dose Finding Phase: Ixazomib 7.0 mg	Ixazomib 7 mg, solution, orally, once on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during lead-in dose finding in NHL participants.	1	6	4	6	6	6
EG003	Phase 2: PSMB1 Positive	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in relapsed Or refractory follicular lymphoma (RRFL) participants.	0	12	4	12	11	12
EG004	Phase 2: PSMB1 Negative	Ixazomib RP2D mg, solution, orally, once weekly on Day 1, 8, and 15 followed by 13 days of rest in a 28-days treatment cycle for a maximum of 29 cycles, or PD or the start of alternate therapies during phase 2 finding in RRFL participants.	0	1	1	1	1	1

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events1 affected7 at risk EG0022 events1 affected6 at risk EG0030 events0 affected12 at risk EG004
Herpes zoster	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Bronchitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Asthenia	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0022 events1 affected6 at risk EG003
Pyrexia	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Local swelling	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected7 at risk EG0020 events0 affected6 at risk EG003
Bile duct obstruction	Hepatobiliary disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Non-Hodgkin's lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Bronchial obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events1 affected7 at risk EG0020 events0 affected6 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0014 events4 affected7 at risk EG00210 events6 affected6 at risk EG00317 events5 affected12 at risk EG0041 events1 affected1 at risk
Nausea	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0005 events2 affected3 at risk EG0014 events3 affected7 at risk EG0027 events3 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0003 events2 affected3 at risk EG0011 events1 affected7 at risk EG00210 events4 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0003 events3 affected3 at risk EG0010 events0 affected7 at risk EG0022 events2 affected6 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected7 at risk EG0022 events2 affected6 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA (18.0)	Systematic Assessment	EG0002 events2 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Fatigue	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0015 events4 affected7 at risk EG0023 events3 affected6 at risk EG003
Asthenia	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected7 at risk EG0020 events0 affected6 at risk EG003
Pyrexia	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected7 at risk EG0020 events0 affected6 at risk EG003
Oedema peripheral	General disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected7 at risk EG0022 events2 affected6 at risk EG003
Chills	General disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Headache	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected7 at risk EG0021 events1 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected7 at risk EG0021 events1 affected6 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events1 affected7 at risk EG0020 events0 affected6 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0011 events1 affected7 at risk EG0024 events2 affected6 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0002 events1 affected3 at risk EG0010 events0 affected7 at risk EG0023 events3 affected6 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events2 affected7 at risk EG0020 events0 affected6 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0003 events3 affected3 at risk EG0012 events2 affected7 at risk EG0023 events3 affected6 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected7 at risk EG0020 events0 affected6 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected7 at risk EG0020 events0 affected6 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0002 events1 affected3 at risk EG0011 events1 affected7 at risk EG0020 events0 affected6 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected7 at risk EG0021 events1 affected6 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected7 at risk EG0020 events0 affected6 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0012 events2 affected7 at risk EG0023 events3 affected6 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0012 events2 affected7 at risk EG0021 events1 affected6 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Neutrophil count decreased	Investigations	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0011 events1 affected7 at risk EG0020 events0 affected6 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected7 at risk EG0020 events0 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0022 events2 affected6 at risk EG003
Hypotension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0000 events0 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Insomnia	Psychiatric disorders	MedDRA (18.0)	Systematic Assessment	EG0001 events1 affected3 at risk EG0010 events0 affected7 at risk EG0021 events1 affected6 at risk EG003
Vision blurred	Eye disorders	MedDRA (18.0)	Systematic Assessment	EG0002 events2 affected3 at risk EG0011 events1 affected7 at risk EG0020 events0 affected6 at risk EG003

Facility	Status	City	State	ZIP	Country	Contacts
		Boston	Massachusetts		United States

ID	Term
D008224	Lymphoma, Follicular
D008223	Lymphoma

ID	Term
D008228	Lymphoma, Non-Hodgkin
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases