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

Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03748953
Collaborator
(none)
30
Enrollment
10
Locations
1
Arm
91.2
Anticipated Duration (Months)
3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Detailed Description

The drug being tested in this study is called ixazomib. Ixazomib is being tested to slow disease progression and improve overall survival in Chinese participants who have newly diagnosed multiple myeloma (NDMM) who have had a major positive response to initial therapy and have not undergone stem cell transplantation (SCT). This study will look at the effect of ixazomib has on the length of time that participants are free of disease progression and their overall survival. After the implementation of Amendment 8, participants who received placebo-matching capsules before unblinding and have not yet experienced disease progression will cross over to receive ixazomib.

The study will enroll approximately 30 patients. Participants will be assigned to a single treatment group

• Ixazomib

All participants will be asked to take one capsule on Days 1, 8, and 15 of every 28-day cycle, for up to 26 cycles or until documented PD or intolerable toxicity, whichever occurs first.

This multi-center trial will be conducted in China. The overall time to participate in this study is until a total of approximately up to 67 months. Participants will make multiple visits to the clinic, and every 4 weeks until the next line of therapy begins for a follow-up assessment.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
30 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
China Continuation: A Single-Arm, Open-Label Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation
Actual Study Start Date :
Jan 24, 2019
Anticipated Primary Completion Date :
Sep 1, 2024
Anticipated Study Completion Date :
Sep 1, 2026

Arms and Interventions

ArmIntervention/Treatment
Experimental: Ixazomib

Ixazomib 3 mg, capsules, orally, once on Days 1, 8 and 15 of every 28-day cycle for Cycle 1 through Cycle 4, during which period if the participants have been tolerated, the dose may be escalated to ixazomib 4 mg, capsules, orally, once on Days 1, 8 and 15 of every 28-day cycle for Cycle 5 through Cycle 26. Participants who received placebo-matching capsules before unblinding and have not yet experienced disease progression will cross over to receive ixazomib.

Drug: Ixazomib
Ixazomib Capsules

Outcome Measures

Primary Outcome Measures

  1. Number of Participants for Each of the Eastern Cooperative Oncology Group (ECOG) Performance Status [First dose of study drug through 30 days after last dose of study drug (approximately 27 months)]

    ECOG performance status will assess participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (>50% of waking hrs), capable of all self-care, unable to carry out any work activities; 3=capable of only limited self-care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5=dead.

  2. Percentage of Participants with Adverse Events (AEs) [First dose of study drug through 30 days after last dose of study drug (approximately 27 months)]

    Adverse events are 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.

  3. Percentage of Participants with Serious Adverse Event (SAE) [First dose of study drug through 30 days after last dose of study drug (approximately 27 months)]

    A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

  4. Number of Participants with Any Markedly Abnormal Standard Safety Laboratory Values [From randomization to every 4 weeks after progressive disease (PD) on next line therapy or death from any cause (approximately 67 months)]

    Clinical laboratory evaluations will be performed by a central laboratory. The number of participants with any markedly abnormal standard safety laboratory values collected throughout study will be reported.

Secondary Outcome Measures

  1. Progression-Free Survival (PFS) [From randomization to every 4 weeks after PD on next line therapy or death from any cause (approximately 67 months)]

    PFS is defined as the time from randomization to the first occurrence of PD as evaluated by an independent review committee (IRC) or death from any cause, whichever occurs first. PD is defined as >=25% increase from lowest value in serum M component or urine M-component; difference between involved and uninvolved free light chain (FLC) levels (absolute increase >10 mg/dL); bone marrow plasma cell percent >/=10%; new bone lesions or soft tissue plasmacytomas development or definite increase in existing bone lesions/soft tissue plasmacytomas size; hypercalcaemia development.

  2. Overall Survival (OS) [From randomization to every 12 weeks during follow-up after PD on next line therapy or death whichever occurs later [approximately 67 months]]

    OS is measured as the time of randomization to the date of death.

  3. Percentage of Participants who Achieve or Maintain Best Response Before PD or up to Subsequent Therapy [From randomization to every 4 weeks after PD on next line therapy or death from any cause (approximately 67 months)]

    Response will be assessed as per IMWG criteria. Best response will include partial responses (PR), very good partial response (VGPR) and complete response (CR). PR is defined as >=50% reduction of serum M-component, urinary M- component by >=90% to <200 mg/24-hour reduction; >=50% in the difference between involved and uninvolved FLC; bone marrow plasma cells (PC) >/= 30%; reduction >/= 50% reduction in the soft tissue size. VGPR is defined as serum or urine M-component detectable by immunofixation but not on electrophoresis; >=90% reduction in serum or urine M-component level <100 mg/24 hour. CR is defined as negative immunofixation on the serum and urine; soft tissue plasmacytomas disappearance; <5% PCs in bone marrow.

  4. Duration of Complete Response (CR) [From randomization to every 4 weeks after PD on next line therapy or death from any cause (approximately 67 months)]

    Duration of CR is defined as the time from the date of randomization or the date of CR to the date of first documentation of PD. CR is defined as negative immunofixation on the serum and urine; soft tissue plasmacytomas disappearance; <5% PCs in bone marrow.

  5. Time to Progression (TTP) [From randomization to every 4 weeks after PD on next line therapy or death from any cause (approximately 67 months)]

    TTP is defined as the time from the date of randomization to the date of first documentation of PD. PD is defined as >=25% increase from lowest value in serum M component or urine M-component; difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL); bone marrow plasma cell percent >/=10%; new bone lesions or soft tissue plasmacytomas development or definite increase in existing bone lesions/soft tissue plasmacytomas size; hypercalcaemia development.

  6. Time to Next-Line Therapy (TTNT) [From randomization to every 4 weeks after PD on next line therapy or death from any cause (approximately 67 months)]

    TTNT is defined as the time from the date of randomization to the date of the first dose of next-line antineoplastic therapy.

  7. Percentage of Participants With A New Primary Malignancy [From randomization to every 4 weeks after PD on next line therapy or death from any cause (approximately 67 months)]

    Percentage of participants with a new primary malignancy will be reported.

  8. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) QLQ-C30 [From randomization to every 4 weeks after PD on next line therapy or death from any cause (approximately 67 months)]

    The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) QLQ-C30 is completed by the participant. The EORTC QLQ-30 contains 30 questions that incorporate 5 functional scales (physical functioning, role functioning, emotional functioning, cognitive functioning, and social functioning), 1 global health status scale, 3 symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The participant answers questions about their health during the past week. There are 28 questions answered on a 4-point scale where 1=not at all (best) to 4=very Much (worst) and 2 questions answered on a 7-point scale where 1=very poor (worst) to 7= excellent (best).

  9. Correlation between Frailty Status and PFS and OS [From randomization to every 12 weeks during follow-up after PD on next line therapy or death whichever occurs later (approximately 67 months)]

    Participants frailty status will be assessed on the basis of 4 components: age (<75, 75- 80, and>80 years correspond to frailty scores of 0, 1, and 2, respectively), the charlson comorbidity scoring system without age weighting (scores of ≤ 1 and ≥ 2 correspond to frailty scores of 0 and 1, respectively), the katz index of independence in activities of daily living (scores of >4 and ≤ 4 correspond to frailty scores of 0 and 1, respectively) and lawton instrumental activities of daily living scale (scores of >5 and ≤ 5 correspond to frailty scores of 0 and 1, respectively). The sum of the 4 frailty scores equals the total frailty score. A total frailty score of 0 corresponds to a frailty status of fit; a total score of 1, to unfit; and a total score of 2 or more, to frail. PFS is defined as the time from randomization to the first occurrence of PD as evaluated by an IRC. OS will be measured as the time from the date of randomization to the date of death.

  10. Plasma Concentration of Ixazomib [Cycle 1 Day 1 (1 and 4 hours post-dose), pre-dose Cycle 1 on Days 8 and 15; Cycle 2 on Days 1 and 8; Cycle 3-5 on Day 1; Cycle 5 on Day 8 (only for those who have dose escalated after Cycle 4); Cycle 6-10 on Day 1, each cycle of 28 days]

  11. Time to Resolution of Peripheral Neuropathy (PN) Events [From First dose date of study drug through 30 days after the last dose of study drug (approximately 27 months)]

    PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the Medical Dictionary for Regulatory Activities (MedDRA). A PN event is considered as resolved if its final outcome is resolved with no subsequent PN event of the same preferred term occurring on the resolution date or the day before and after. Time to resolution is defined as the time from the initial onset date (inclusive) to the resolution date for resolved events.

  12. Time to Improvement of PN Events [From First dose date of study drug through 30 days after the last dose of study drug (approximately 27 months)]

    PN is defined as the treatment-emergent adverse event in the high-level term of peripheral neuropathies not elsewhere classified (NEC) according to the MedDRA. A PN event is considered to be improved if the event improves from the maximum grade; that is, all the grades recorded after the maximum grade are less than the maximum grade. Time to improvement is defined as the time from the initial onset date (inclusive) of the maximum grade to the first onset date that the toxicity grade is below the maximum grade with no higher grade thereafter, or the resolution date, whichever occurs first.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Adult male or female participants aged 18 years or older with a confirmed diagnosis of symptomatic NDMM according to standard criteria.

  2. 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.

  3. 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.

  4. 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 (eg, calendar, ovulation,symptothermal, postovulation methods] and withdrawal are not acceptablemethods of contraception.)

Male participants, even if surgically sterilized (ie, 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 [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)

  1. 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.

  2. Has availability of complete documentation for:

  3. Details of initial disease state, initial therapy, and response

  4. Cytogenetic assessment at diagnosis (cytogenetic assessment performed after diagnosis must be approved by a Millennium project clinician or designee)

  5. ISS staging at diagnosis (requiring beta 2-microglobulin and serum albumin results).

  6. Has eastern cooperative oncology group performance status of 0 to 2.

  7. Suitable venous access for the study-required blood sampling and consent for the specific amounts that will be taken.

  8. Participant is willing and able to adhere to the study visit schedule and other protocol requirements including blood sampling and bone marrow aspiration.

  9. Participants must meet the following clinical laboratory criteria at study entry:

  10. Absolute neutrophil count (ANC) ≥1,000/mm3 without growth factor support and platelet count ≥ 75,000/mm3. Platelet transfusions to help participants meet eligibility criteria are not allowed within 3 days before randomization.

  11. Total bilirubin≤1.5the upper limit of the normal range (ULN). 3. Alanine aminotransferase and aspartate aminotransferase≤3ULN. 4. Calculated creatinine clearance≥ 30 mL/min (using the Cockroft-Gault equation.

Exclusion Criteria:
  1. Has multiple myeloma that has relapsed after, or was not responsive to, initial therapy.

  2. Had prior stem-cell transplantation (SCT).

  3. Has radiotherapy within 14 days before randomization.

  4. Had diagnosed or treated for another malignancy within 5 years before randomization 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.

  5. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.

  6. Has major surgery within 14 days before randomization.

  7. Has central nervous system involvement.

  8. Infection requiring IV antibiotic therapy or other serious infection within 14 days before randomization.

  9. 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.

  10. 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.

  11. Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort within 14 days before randomization.

  12. Ongoing or active infection, known human immunodeficiency virus positive, active hepatitis B or C infection.

  13. 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 (eg, peripheral neuropathy (PN) that is Grade 1 with pain or Grade 2 or higher of any cause).

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

  15. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.

  16. Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or GI procedure that could interfere with the oral absorption or tolerance of treatment.

  17. Treatment with any investigational products within 30 days before randomization.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Beijing Chaoyang Hospital Capital Medical UniversityBeijingBeijingChina100020
2Peking University Third HospitalBeijingBeijingChina100191
3Peking Union Medical College HospitalBeijingBeijingChina100730
4Tongji Hospital Tongji Medical College Huazhong University of Science and TechnologyWuhanHubeiChina430030
5Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)NanjingJiangsuChina210029
6Shengjing Hospital of China Medical UniversityShenyangLiaoningChina110004
7Renji Hospital Shanghai Jiaotong University School of MedicineShanghaiShanghaiChina200001
8Shanghai Chang Zheng HospitalShanghaiShanghaiChina200003
9Ruijin Hospital Shanghai Jiaotong University School of MedicineShanghaiShanghaiChina200025
101st Affiliated Hospital of Zhejiang UniversityHangzhouZhejiangChina310003

Sponsors and Collaborators

  • Millennium Pharmaceuticals, Inc.

Investigators

  • Study Director: Medical Director Clinical Science, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT03748953
Other Study ID Numbers:
  • C16021 CSC
  • 2014-001394-13
  • NCT04371770
First Posted:
Nov 21, 2018
Last Update Posted:
Oct 8, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Millennium Pharmaceuticals, Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 8, 2021