UMIN-CTR Clinical Trial

Public title

An Open-label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Ixazomib in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma Initially Treated with an Injection of Proteasome Inhibitor-Based Therapy

Acronym

A Study to Evaluate the Efficacy and Safety of Ixazomib in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma Initially Treated with an Injection of Proteasome Inhibitor-Based Therapy

Scientific Title

An Open-label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of Ixazomib in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma Initially Treated with an Injection of Proteasome Inhibitor-Based Therapy

Scientific Title:Acronym

A Study to Evaluate the Efficacy and Safety of Ixazomib in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma Initially Treated with an Injection of Proteasome Inhibitor-Based Therapy

Region

Japan

Condition

Relapsed and/or Refractory Multiple Myeloma

Classification by specialty

Hematology and clinical oncology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To investigate the efficacy and safety of long-term administration of the oral proteasome inhibitor ixazomib as part of ixazomib in combination with lenalidomide and dexamethasone (IRd) therapy in patients with relapsed and/or refractory multiple myeloma (RRMM) treated initially with an injectable proteasome inhibitor-based therapy.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase IV

Primary outcomes

Progression-free survival (PFS) rate at 12 months from the start of study treatment

Key secondary outcomes

Overall survival (OS) from the start of study treatment
PFS from the start of study treatment
Proportion of patients who achieved very good partial response (VGPR) or better
Rate of minimal residual disease (MRD) in bone marrow in patients who achieved complete response (CR)
Best response
Overall response rate (ORR)
Proportion of patients continuing treatment with ixazomib at 12 months from the start of study treatment
Duration of response (DOR)
Patient-reported outcome: health-related quality of life (HRQoL), as evaluated by the EORTC QLQ-C30 and MY-20 instruments
Evaluation of Quality-Adjusted Life-Years (QALYs)
Healthcare resource utilization (HCRU)
Relative Dose Intensity (RDI)
Bone evaluation
AEs

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Treatment Period I:
Bortezomib + Lenalidomide + Dexamethasone or
Carfilzomib + Lenalidomide + Dexamethasone
Treatment Period II:
Ixazomib + Lenalidomide + Dexamethasone

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

Treatment Period I
1. Men and women of age 20 years or older at the time of enrollment
2. Patients with RRMM
3. Patients who are planned to start combination therapy with bortezomib, lenalidomide, and dexamethasone (VRd), or combination therapy with carfilzomib, lenalidomide, and dexamethasone (KRd) as second, third or fourth line of treatment
4. Patients with measurable disease defined by one or more of the following three measurements
-Serum M-protein: >= 1g/dL (>= 10g/L)
-Urine M-protein: >= 200mg/24 hours
-Serum free light chain assay: involved free light chain concentration >= 10mg/dL (>= 100mg/L) provided that the serum free light chain ratio is abnormal
5. Patients with ECOG performance status (PS) 0-2; however, patients with ECOG PS 3 are eligible if they only have symptoms associated with bone lesions.
6. Patients who are considered by the principal investigator or investigator not to be eligible for transplant; or, if considered eligible for transplant, patients who are planned not to undergo transplant for at least 12 months after the start of the study treatment
7. Patients must be registered with, and comply with, the guidelines of the lenalidomide management program
8. Patients who, before implementing procedures related to clinical research (excluding standard medical practices), understand that they can withdraw consent at any time without suffering from disadvantages to future treatments, and can provide written informed consent
Treatment Period II
9. Patients must have received an injectable proteasome inhibitor (bortezomib or carfilzomib) in each treatment cycle of Treatment Period I

Key exclusion criteria

Treatment Period I
1. Patients with another active malignancy
2. Patients with poorly controlled active thrombosis
3. Patients who have participated in a clinical trial of ixazomib or have been treated with ixazomib
4. Patients who were refractory to either treatment regimen based on lenalidomide and/or proteasome inhibitor(s)
5. Patients with ongoing or active systemic infection, known hepatitis B virus infection, known hepatitis C virus infection, or known positivity to human immunodeficiency virus (HIV)
6. Patients who underwent major surgery within 14 days prior to enrollment to Treatment Period I
7. Patients who received radiation therapy within 14 days prior to enrollment to Treatment Period I
8. Patients who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade >=2 peripheral neuropathy
9. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmia, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months before enrollment to Treatment Period I
10. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment into Treatment Period I
11. Patients with central nervous system involvement
Treatment Period II
12. Patients who do not achieve at least a minimal response (MR) to VRd or KRd in Treatment Period I per the International Myeloma Working Group (IMWG) response criteria, 2014 revision
13. Patients who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade >=2 peripheral neuropathy during Treatment Period I
14. Patients with evidence of uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmia, symptomatic congestive heart failure, unstable angina, or myocardial infarction during Treatment Period I
15. Patients using potent CYP3A4 inducing agents, or gingko biloba or St. John's wort

Target sample size

47

Name of lead principal investigator

1st name
Middle name
Last name	1. Kenshi Suzuki, 2. Takaaki Chou, 3. Naoki Takezako, 4. Makoto Sasaki

Organization

1. Japanese Red Cross Medical Center
2. Niigata Cancer Center Hospital
3. National Hospital Organization Disaster Medical Center
4. Juntendo University Hospital

Division name

1. Myeloma and Amyloidosis Center, 2. Internal Medicine, 3. Hematology, 4. Hematology

Zip code

Address

1. 4-1-22 Hiroo, shibuya-ku, Tokyo 2. 2-15-3 Kawagishi-cho, Chuo-Ku, Niigata-shi, Niigata, 3. 3256 Midori-cho, Tachikawa-shi, Tokyo, 4. 3-1-3 Hongo, Bunkyo-ku, Tokyo

TEL

03-6779-8013

Email

c16043_office@cmic.co.jp

Name of contact person

1st name
Middle name
Last name	Takeda Study Registration Call Center

Organization

Takeda Pharmaceutical Company Limited

Division name

Strategic Medical Research Planning, Global Medical Affairs-Japan

Zip code

Address

1-1, Nihonbashihoncho 2-chome, Chuo-ku, Tokyo

TEL

03-3278-2111

Homepage URL

Email

c16043_office@cmic.co.jp

Institute

Takeda Pharmaceutical Company Limited

Institute

Department

Personal name

Organization

Takeda Pharmaceutical Company Limited

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

YES

Study ID_1

NCT03416374

Org. issuing International ID_1

A service of the U.S. National Institutes of Health

Study ID_2

JapicCTI-183839

Org. issuing International ID_2

Japan Pharmaceutical Information Center

IND to MHLW

Institutions

Date of disclosure of the study information

2018

Year

01

Month

24

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

2018

Year

01

Month

15

Day

Date of IRB

2018

Year

01

Month

18

Day

Anticipated trial start date

2018

Year

03

Month

12

Day

Last follow-up date

2021

Year

05

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

01

Month

24

Day

Last modified on

2020

Year

06

Month

01

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035326