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

NCT ID: NCT03416374

Last Updated: 2022-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-18
• Study Completion Date: 2021-05-28

Brief Summary

The purpose of this study is 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.

Detailed Description

The drug being tested in this study is called Ixazomib. Ixazomib is being tested to treat people who have RRMM. This study will look at the effectiveness and safety of IRd in participants with RRMM previously receiving an injectable proteasome inhibitor-based therapy. This study consists of two treatment periods, Treatment Period I and Treatment Period II.

The study will enroll 47 patients. All participants will receive following treatment:

• Combination therapy with Bortezomib + Lenalidomide + Dexamethasone (VRd) or combination therapy with Carfilzomib + Lenalidomide + Dexamethasone (KRd), standard recommended dose according to the package insert of each drug, as Treatment Period I, followed by Combination therapy with Ixazomib 4.0 mg + Lenalidomide 25 mg + Dexamethasone 40 mg (IRd) as Treatment Period II

At start of this study, combination therapy of VRd or KRd will be decided by investigator as Treatment Period I after the baseline evaluations. After the start of Treatment Period I, a participant's eligibility for Treatment Period II is then determined 3 cycles. Participants who meet these eligibility criteria II subsequently continue into Treatment Period II and receive IRd.

This multi-center trial will be conducted in Japan. It is anticipated that the treatment phase of this study will last up to 39 months, including 18 months for enrollment. Participants will make multiple visits to the clinic in treatment period, and follow-up period including a follow-up assessment after last dose of study drug.

Conditions

Relapsed and/or Refractory Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination Therapy + Ixazomib Therapy

Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)

Group Type: EXPERIMENTAL

Ixazomib

Intervention Type: DRUG

Ixazomib capsules

Bortezomib

Intervention Type: DRUG

Bortezomib injections

Carfilzomib

Intervention Type: DRUG

Carfilzomib intravenous infusions

Lenalidomide

Intervention Type: DRUG

Lenalidomide capsules

Dexamethasone

Intervention Type: DRUG

Dexamethasone tablets

Interventions

Ixazomib

Ixazomib capsules

Intervention Type: DRUG

Bortezomib

Bortezomib injections

Intervention Type: DRUG

Carfilzomib

Carfilzomib intravenous infusions

Intervention Type: DRUG

Lenalidomide

Lenalidomide capsules

Intervention Type: DRUG

Dexamethasone

Dexamethasone tablets

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Eligibility for Treatment Period I

1. Men and women of age 20 years or older at the time of enrollment.

2. Participants with RRMM.

3. Participants who are planned to start combination therapy with bortezomib, lenalidomide, and dexamethasone (VRd) or carfilzomib, lenalidomide, and dexamethasone (KRd) as second, third or fourth line of treatment.

4. Participants with measurable disease defined by one or more of the following three measurements.

• Serum M-protein: ≥0.5 gram (g)/ deciliter (dL) (≥ 5 g/ liter [L])
• Urine M-protein: ≥ 200 milligram (mg)/24 hours
• Serum free light chain assay: involved free light chain concentration ≥ 10 mg/dL (≥ 100 mg/L) provided that the serum free light chain ratio is abnormal

5. Participants with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2; however, participants with ECOG PS 3 are eligible if they only have symptoms associated with bone lesions.

6. Participants who are considered by the principal investigator or investigator not to be eligible for transplant; or, if considered eligible for transplant, participants who are planned not to undergo transplant for at least 12 months after the start of the study treatment.

7. Participants must be registered with, and comply with, the guidelines of the lenalidomide management program.

8. Participants 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.

Eligibility for Treatment Period II

9. Participants must have received an injectable proteasome inhibitor (bortezomib or carfilzomib) in each treatment cycle of Treatment Period I.

Exclusion Criteria

Eligibility for Treatment Period I

1. Women who are nursing or pregnant.

2. Participants with another active malignancy, i.e. synchronous active malignancy or previous malignancy with a disease-free period of less than 5 years, except for participants with carcinoma in situ (intraepithelial carcinoma) or intramucosal carcinoma judged to be cured by topical treatment.

3. Participants with poorly controlled active thrombosis.

4. Participants who have participated in a clinical trial of ixazomib or have been treated with ixazomib.

5. Participants who were refractory to either treatment regimen based on lenalidomide and/or proteasome inhibitor(s).

Note: Refractory MM is defined as PD on therapy or PD within 60 days after the last dose of a given therapy. Participants who have disease progressed 60 days after the last dose of a given therapy will be considered as relapsed in this study.

6. Participants with ongoing or active systemic infection, known hepatitis B virus infection, known hepatitis C virus infection, or known positivity to human immunodeficiency virus (HIV).

7. Participants who underwent major surgery within 14 days prior to enrollment to Treatment Period I. Surgery for bone lesions is not considered as major surgery.

8. Participants who received radiation therapy within 14 days prior to enrollment to Treatment Period I. If the radiation field is small, 7 days is considered as a sufficient interval between radiation therapy and chemotherapy.

9. Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade ≥2 peripheral neuropathy.

10. 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.

11. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment into Treatment Period I.

12. Participants with central nervous system involvement.

13. Inability to swallow oral medications, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal conditions that could interfere with the oral absorption or tolerance of treatment.

14. Psychiatric illness/social situation that would limit compliance with study requirements.

15. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

Eligibility for Treatment Period II

16. Participants 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.

17. Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade ≥2 peripheral neuropathy during Treatment Period I.

18. Participants 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.

19. Participants using potent CYP3A4 inducing agents (rifampicin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or gingko biloba or St. John's wort.

20. Participants with hypersensitivity to any of the IRd study medications, their analogs, or excipients contained in IRd.

21. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Takeda

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Kameda Medical Center

Kamogawa, Chiba, Japan

The Jikei University Kashiwa Hospital

Kashiwa, Chiba, Japan

Ogaki Municipal Hospital

Ōgaki, Gifu, Japan

Gunma University Hospital

Maebashi, Gunma, Japan

Shibukawa Medical Center

Shibukawa, Gunma, Japan

Kobe city Medical Center General Hospital

Kobe, Hyōgo, Japan

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

Iwate Medical University

Morioka, Iwate, Japan

Yokohama Municipal Citizen's Hospital

Yokohama, Kanagawa, Japan

Suwa Red Cross Hospital

Suwa, Nagano, Japan

Dokkyo Medical University

Koshigaya, Saitama, Japan

Juntendo University Hospital

Bunkyo-ku, Tokyo, Japan

Nippon Medical School Hospital

Bunkyo-ku, Tokyo, Japan

Nihon University Itabashi Hospital

Itabashi-ku, Tokyo, Japan

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan

The Jikei University Hospital

Minato-ku, Tokyo, Japan

Kyorin University Hospital

Mitaka, Tokyo, Japan

Japanese Red Cross Medical Center

Shibuya-ku, Tokyo, Japan

Tokyo Disaster Medical Center

Tachikawa, Tokyo, Japan

Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

Hiroshima, , Japan

Kyoto Kuramaguchi Medical Center

Kyoto, , Japan

Niigata Cancer Center Hospital

Niigata, , Japan

Osaka Red Cross Hospital

Osaka, , Japan

Countries

Japan

References

Abe Y, Sasaki M, Takezako N, Ito S, Suzuki K, Handa H, Chou T, Yoshida T, Mori I, Shinozaki T, Suzuki K. Efficacy and Safety of Ixazomib Plus Lenalidomide and Dexamethasone Following Injectable PI-Based Therapy in Relapsed/Refractory Multiple Myeloma. Ann Hematol. 2023 Sep;102(9):2493-2504. doi: 10.1007/s00277-023-05212-7. Epub 2023 Jun 21.

Reference Type: DERIVED

PMID: 37341778 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.takeda.com/study-detail/5f6b60204db2bf003ab49579

To obtain more information on the study, click here/on this link

Other Identifiers

U1111-1207-0061

Identifier Type: OTHER

Identifier Source: secondary_id

JapicCTI-183839

Identifier Type: REGISTRY

Identifier Source: secondary_id

C16043

Identifier Type: -

Identifier Source: org_study_id