Study to determine whether ixazomib as maintenance therapy has an effect on progression free survival and compared to placebo in patients with newly diagnosed multiple myeloma who have not been treated with stem-cell transplantation

• Register: EUCTR
• Last refreshed on: 9 May 2022
• Main ID: EUCTR2014-001394-13-GR
• Date of registration: 07/08/2015
• Prospective Registration: No
• Primary sponsor: Takeda Development Center Americas, Inc.
• Public title: Study to determine whether ixazomib as maintenance therapy has an effect on progression free survival and compared to placebo in patients with newly diagnosed multiple myeloma who have not been treated with stem-cell transplantation
• Scientific title: A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study of Oral Ixazomib Maintenance Therapy After Initial Therapy in Patients With Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation
• Date of first enrolment: 30/04/2015
• Target sample size: 706
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001394-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Croatia, Czech Republic, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Mexico, Poland, Portugal, Russian Federation, Serbia, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Drug Information Call Center
• Affiliation: Takeda Development Center Americas, Inc.

• Name: Drug Information Call Center
• Affiliation: Takeda Development Center Americas, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Adult male or female patients aged 18 years or older with a confirmed diagnosis of symptomatic NDMM according to standard criteria.
2. Completed 6 to 12 months ( ±2 weeks) of initial therapy, during which the patient was treated to best response, defined as the best response maintained for 2 cycles after the M-protein nadir is reached.
3. Documented major response (PR, VGPR, CR) according to the IMWG uniform response criteria, version 2011, after this initial therapy.
4. Female patients 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 subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
Male patients, 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 subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
5. 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 patient at any time without prejudice to future medical care.
6. Complete documentation of the details of the initial therapy before randomization including cytogenetics and ISS is available.
7. Eastern Cooperative Oncology Group Performance Status of 0 to 2
8. Suitable venous access for the study-required blood sampling and consent for the specific amounts that will be taken.
9. Patient is willing and able to adhere to the study visit schedule and other protocol requirements including blood sampling and bone marrow aspiration.
10. Patients must meet the following clinical laboratory criteria at study entry:
-Absolute neutrophil count (ANC) =1,000/mm3 without growth factor support and platelet count = 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before randomization.
-Total bilirubin = 1.5 X the upper limit of the normal range (ULN).
-Alanine aminotransferase and aspartate aminotransferase = 3 X ULN.
-Calculated creatinine clearance = 30 mL/min (using the Cockroft-Gault equation
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 68
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 638

Exclusion criteria:
1. Multiple myeloma that has relapsed after, or was not responsive to, initial therapy.
2. Prior SCT.
3. Radiotherapy within 14 days before randomization.
4. Diagnosed or treated for another malignancy within 5 years before randomization or previous diagnosis with another malignancy. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
5. Female patients who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period.
6. Major surgery within 14 days before randomization.
7. Central nervous system involvement.
8. Infection requiring IV antibiotic therapy or other serious infection within 14 days before randomization.
9. Diagnosis of Waldenstrom’s macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) 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 inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole), or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use of Ginkgo biloba or 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. Comorbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens (eg, 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Newly Diagnosed Multiple Myeloma Not Treated With Stem Cell Transplantation
MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Ixazomib Capsules 0.5 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ixazomib citrate
CAS Number: 1239908-20-3
Other descriptive name: MLN9708
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Ixazomib Capsules 2.3 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ixazomib citrate
CAS Number: 1239908-20-3
Other descriptive name: MLN9708
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.3-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Ixazomib Capsules 3 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ixazomib citrate
CAS Number: 1239908-20-3
Other descriptive name: MLN9708
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Ixazomib Capsules 4 mg
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: ixazomib citrate
CAS Number: 1239908-20-3
Other descriptive name: MLN9708
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To determine the effect of ixazomib maintenance therapy on progression-free survival (PFS), defined as the time from randomization to progressive disease (PD) or death from any cause, compared with placebo, in patients with NDMM who have had a major response - defined as complete response (CR), very good partial response (VGPR), or partial response (PR) - to initial therapy and who have not undergone SCT.
Assessment of several study objectives was completed at the time of the first interim analysis (IA). Upon implementation of Amendment 07, data
collected after the first IA will be used to assess OS (overall survival), PFS2 (progression-free survival), patient reported outcomes, and safety only.
The above mentioned objective is retained for reference only.

Secondary Objective: To determine the effect of ixazomib maintenance therapy on overall survival (OS) compared with placebo.
Assessment of several study objectives was completed at the time of the first interim analysis (IA). Upon implementation of Amendment 07, data
collected after the first IA will be used to assess OS (overall survival), PFS2 (progression-free survival), patient reported outcomes, and safety only.
The above mentioned objective is retained for reference only.

Primary end point(s): Progression-free survival, 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.
Assessment of several study endpoints was completed at the time of the first interim analysis (IA). Upon implementation of Amendment 07, data
collected after the first IA will be used to assess OS (overall survival), PFS2 (progression-free survival), patient reported outcomes, and safety only.
The above mentioned endpoint is retained for reference only.

Timepoint(s) of evaluation of this end point: first occurrence of PD

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: date of death

Secondary end point(s): Overall survival, measured as the time of randomization to the date of death.
Assessment of several study endpoints was completed at the time of the first interim analysis (IA). Upon implementation of Amendment 07, data
collected after the first IA will be used to assess OS (overall survival), PFS2 (progression-free survival), patient reported outcomes, and safety only.
The above mentioned endpoint is retained for reference only.

Secondary ID(s)

2014-001394-13-DE

C16021

Source(s) of Monetary Support

Takeda Development Center Americas, Inc.

Ethics review

Status: Approved
Approval date: 30/04/2015
Contact: