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

NCT03416374 | Completed Phase 4 Results FDA Drug

• 3 other identifiers: C16043U1111-1207-0061JapicCTI-183839
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 23

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.

Conditions

Relapsed and/or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment

  PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved free light chain (FLC) levels increase \>10 mg/dl or bone marrow plasma cell ≥10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia.

  Up to 12 months

Secondary Outcomes (18)

• Overall Survival (OS) From the Start of Study Treatment

  Up to 39 months as a maximum

• PFS From the Start of Study Treatment

  Up to 39 months as a maximum

• Percentage of Participants Who Achieved VGPR or Better (CR + VGPR)

  Up to 39 months as a maximum

• Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR

  Up to 39 months as a maximum

• Percentage of Participants Who Achieve or Maintain Any Best Response

  Up to 39 months as a maximum

Study Arms (1)

Combination Therapy + Ixazomib Therapy

EXPERIMENTAL

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)

Drug: Ixazomib; Drug: Bortezomib; Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

Ixazomib capsules

Combination Therapy + Ixazomib Therapy

Bortezomib DRUG

Bortezomib injections

Combination Therapy + Ixazomib Therapy

Carfilzomib DRUG

Carfilzomib intravenous infusions

Combination Therapy + Ixazomib Therapy

Lenalidomide DRUG

Lenalidomide capsules

Combination Therapy + Ixazomib Therapy

Dexamethasone DRUG

Dexamethasone tablets

Combination Therapy + Ixazomib Therapy

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligibility for Treatment Period I
• Men and women of age 20 years or older at the time of enrollment.
• Participants with RRMM.
• 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.
• 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
• 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.
• 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.
• Participants must be registered with, and comply with, the guidelines of the lenalidomide management program.
• 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
• Participants must have received an injectable proteasome inhibitor (bortezomib or carfilzomib) in each treatment cycle of Treatment Period I.

You may not qualify if:

• Eligibility for Treatment Period I
• Women who are nursing or pregnant.
• 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.
• Participants with poorly controlled active thrombosis.
• Participants who have participated in a clinical trial of ixazomib or have been treated with ixazomib.
• 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.
• 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).
• 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.
• 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.
• Participants who experience Grade 1 peripheral neuropathy accompanied by pain, or Grade ≥2 peripheral neuropathy.
• 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.
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before enrollment into Treatment Period I.
• Participants with central nervous system involvement.
• 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.

Sponsors & Collaborators

• Takeda: lead

Study Sites (23)

Kameda Medical Center

Kamogawa, Chiba, Japan

Location

The Jikei University Kashiwa Hospital

Kashiwa, Chiba, Japan

Location

Ogaki Municipal Hospital

Ōgaki, Gifu, Japan

Location

Gunma University Hospital

Maebashi, Gunma, Japan

Location

Shibukawa Medical Center

Shibukawa, Gunma, Japan

Location

Kobe city Medical Center General Hospital

Kobe, Hyōgo, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

Location

Iwate Medical University

Morioka, Iwate, Japan

Location

Yokohama Municipal Citizen's Hospital

Yokohama, Kanagawa, Japan

Location

Suwa Red Cross Hospital

Suwa, Nagano, Japan

Location

Dokkyo Medical University

Koshigaya, Saitama, Japan

Location

Juntendo University Hospital

Bunkyo-ku, Tokyo, Japan

Location

Nippon Medical School Hospital

Bunkyo-ku, Tokyo, Japan

Location

Nihon University Itabashi Hospital

Itabashi-ku, Tokyo, Japan

Location

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan

Location

The Jikei University Hospital

Minato-ku, Tokyo, Japan

Location

Kyorin University Hospital

Mitaka, Tokyo, Japan

Location

Japanese Red Cross Medical Center

Shibuya-ku, Tokyo, Japan

Location

Tokyo Disaster Medical Center

Tachikawa, Tokyo, Japan

Location

Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

Hiroshima, Japan

Location

Kyoto Kuramaguchi Medical Center

Kyoto, Japan

Location

Niigata Cancer Center Hospital

Niigata, Japan

Location

Osaka Red Cross Hospital

Osaka, Japan

Location

Related Publications (1)

• 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.

  PMID: 37341778 DERIVED

Related Links

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

MeSH Terms

Interventions

ixazomib; Bortezomib; carfilzomib; Lenalidomide; Dexamethasone

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: January 31, 2018
• Study Start: February 18, 2018
• Primary Completion: May 28, 2021
• Study Completion: May 28, 2021
• Last Updated: September 27, 2022
• Results First Posted: August 22, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

JP (23)