Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Participants With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation (SCT)

NCT03748953 | Completed Phase 3 Results

• 2 other identifiers: C16021 CCS2014-001394-13
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study is to determine the long-term safety and tolerability of ixazomib maintenance therapy.

Conditions

Multiple Myeloma

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (4)

• Number of Participants Categorized According to Performance Status (PS) Based on Eastern Cooperative Oncology Group (ECOG) PS

  ECOG PS was used to assess physical health of participants. ECOG PS grade:0= fully active, able to carry on all pre-disease performance without restriction,1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature 2= ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours, 3= capable of only limited self-care, 4= completely disabled, cannot carry on any selfcare, totally confined to bed or chair confined to bed or chair more than 50% of waking hours and 5= dead. Only those categories with non-zero values were reported.

  Month 25

• Percentage of Participants Receiving Ixazomib With Treatment-emergent Adverse Events (TEAEs)

  Adverse events (AEs) were defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug. A TEAE was defined as an AE that started or worsened after first study drug administration and within 30 days of last dose of study drug. Percentages are rounded off to the nearest whole number.

  Up to 58.4 months

• Percentage of Participants Receiving Ixazomib With Treatment-emergent Serious Adverse Events (SAEs)

  AEs were defined as any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product reported from first dose of study drug through 30 days after the last dose of study drug. A TEAE was defined as an AE that started or worsened after first study drug administration and within 30 days of last dose of study drug. An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital abnormality or birth defect, or is an important medical event. Percentages are rounded off to the nearest whole number.

  Up to 58.4 months

• Number of Participants Receiving Ixazomib With Clinically Significant Changes in Safety Laboratory Values

  Clinical laboratory assessments included hematology, serum chemistry, and urinalysis. Any clinically significant changes in the clinical laboratory value over time based on the investigator's interpretation were reported.

  Up to 58.4 months

Secondary Outcomes (13)

• Progression-Free Survival (PFS)

  From the first dose of study drug to every 4 weeks until PD or death from any cause (up to 58.4 months)

• Overall Survival (OS)

  From the first dose of study drug to every 12 weeks during follow-up after PD or next line therapy or death whichever occurred later (up to 58.4 months)

• Percentage of Participants Who Achieved or Maintained Best Response Before PD or up to Subsequent Therapy

  Up to 58.4 months

• Duration of Complete Response (CR)

  Up to 58.4 months

• Time to Progression (TTP)

  Up to 58.4 months

Study Arms (1)

Ixazomib

EXPERIMENTAL

Participants received ixazomib 3 milligrams (mg), capsules, orally, once on Days 1, 8, and 15 for Cycles 1 through 4, during which if the participants tolerated the initial dose, the dose was escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 for Cycles 5 through 26, or until documented PD or intolerable toxicity, whichever occurred first (cycle length=28 days).

Drug: Ixazomib

Interventions

Ixazomib DRUG

Ixazomib Capsules

Ixazomib

Eligibility Criteria

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

You may qualify if:

• Adult male or female participants aged 18 years or older with a confirmed diagnosis of symptomatic NDMM according to standard criteria.
• Has completed 6 to 12 months (±2 weeks) of initial therapy, during which the participant was treated to best response, defined as the best response maintained for 2 cycles after the M-protein nadir is reached.
• Has documented major response (partial response \[PR\], very good partial response \[VGPR\], complete response \[CR\]) according to the international myeloma working group (IMWG) uniform response criteria, version 2011, after this initial therapy.
• Female participants who:
• Are postmenopausal for at least 1 year before the screening visit, OR Are surgically sterile, OR If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, or Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[e.g., calendar, ovulation,symptothermal, postovulation methods\] and withdrawal are not acceptable methods of contraception.)
• Male participants, even if surgically sterilized (i.e., status postvasectomy), who:
• Agree to practice effective barrier contraception during the entire study Treatment period and through 90 days after the last dose of study drug, or Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[e.g., calendar, ovulation, symptothermal, postovulation methods for the female partner\] and withdrawal are not acceptable methods of contraception.)
• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
• Has availability of complete documentation for:
• Details of initial disease state, initial therapy, and response
• Cytogenetic assessment at diagnosis (cytogenetic assessment performed after diagnosis must be approved by a Takeda project clinician or designee)
• International Staging System (ISS) staging at diagnosis (requiring beta 2-microglobulin and serum albumin results).
• Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
• Suitable venous access for the study-required blood sampling and consent for the specific amounts that will be taken.
• Participant is willing and able to adhere to the study visit schedule and other protocol requirements including blood sampling and bone marrow aspiration.

You may not qualify if:

• Has multiple myeloma that relapsed after, or was not responsive to, initial therapy.
• Had prior stem-cell transplantation (SCT).
• Has radiotherapy within 14 days before enrollment.
• Had been diagnosed or treated for another malignancy within 5 years before enrollment or previously diagnosed with another malignancy with evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
• Has major surgery within 14 days before enrollment.
• Has central nervous system involvement.
• Infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before enrollment.
• Has diagnosis of Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, uncontrolled congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
• Systemic treatment with strong cytochrome P450 (CYP3A) inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort within 14 days before enrollment.
• Ongoing or active infection, known human immunodeficiency virus positive, active hepatitis B or C infection.
• Has comorbid systemic illnesses or other severe concurrent disease that, 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 (e.g., peripheral neuropathy (PN) that is Grade 1 with pain or Grade 2 or higher of any cause).
• Psychiatric illness/social situation that would limit compliance with study requirements.
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (10)

Beijing Chaoyang Hospital Capital Medical University

Beijing, Beijing Municipality, 100020, China

Location

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

Location

Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)

Nanjing, Jiangsu, 210029, China

Location

Shengjing Hospital of China Medical University

Shenyang, Liaoning, 110004, China

Location

Renji Hospital Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200001, China

Location

Shanghai Chang Zheng Hospital

Shanghai, Shanghai Municipality, 200003, China

Location

Ruijin Hospital Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

1st Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, 310003, China

Location

Related Links

• To obtain more information about this study, click this link.

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: November 21, 2018
• Study Start: January 24, 2019
• Primary Completion: December 6, 2023
• Study Completion: December 6, 2023
• Last Updated: March 21, 2025
• Results First Posted: March 21, 2025

Record last verified: 2025-03

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

CN (10)