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Trial registered on ANZCTR


Registration number
ACTRN12616000894493
Ethics application status
Approved
Date submitted
22/06/2016
Date registered
7/07/2016
Date last updated
3/07/2019
Date data sharing statement initially provided
3/07/2019
Date results information initially provided
3/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A prospective, multi-centre, single arm, phase 2 assessment of the efficacy and safety of the combination of ixazomib, thalidomide and dexamethasone (ITD) for relapsed and/or refractory multiple myeloma after 1 to 3 prior lines of therapy.
Scientific title
A prospective, multi-centre, single arm, phase 2 assessment of the efficacy and safety of the combination of ixazomib, thalidomide and dexamethasone (ITD) for relapsed and/or refractory multiple myeloma after 1 to 3 prior lines of therapy.
Secondary ID [1] 289512 0
Protocol X16078
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 299217 0
Condition category
Condition code
Cancer 299225 299225 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Ixazomib - 4mg - Days 1, 8 and 15 of 28 day cycle - patient to continue on treatment unitl unacceptable toxicity/adverse event, relapse/progressive disease, consent withdrawal or death - oral tablet
Thalidomide - 100mg - Days 1-28 of 28 day cycle - patient to continue on treatment unitl unacceptable toxicity/adverse event, relapse/progressive disease, consent withdrawal or death - oral tablet
Dexamethasone - 40mg - Days 1, 8, 15, 22 of 28 day cycle - patient to continue on treatment unitl unacceptable toxicity/adverse event, relapse/progressive disease, consent withdrawal or death - oral tablet
Adherence monitored through medication reconciliation.
Intervention code [1] 295104 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 298706 0
To investigate the efficacy of ITD combination therapy in relapsed/refractory multiple myeloma patients as assessed using International Myeloma Working Group(IMWG) response criteria.
Timepoint [1] 298706 0
Achievement of an overall response rate (ORR) defined as complete response + very good partial response + partial response (CR + VGPR + PR) assessed at the end of each cycle of treatment.
Primary outcome [2] 298707 0
To investigate the safety (incidence and severity of adverse events both reported and through review of medical records) and tolerability (total dose and percentage of planned dose delivered in each cycle) of ITD combination therapy
Timepoint [2] 298707 0
At the end of each cycle for the duration of treatment.
Secondary outcome [1] 325018 0
Clinical benefit rate (CBR) defined as overall response rate (ORR) + minimal response (MR) as defined by IMWG response criteria.
Timepoint [1] 325018 0
Achievement of ORR or MR as assessed at the completion of each cycle of treatment.
Secondary outcome [2] 325019 0
Duration of response (DOR) as per IMWG response criteria.
Timepoint [2] 325019 0
Time from best response to progression of disease. Follow-up will continue until all patients remaining on study have been followed up for at least 12 months.
Secondary outcome [3] 325020 0
Progression free survival (PFS) as per IMWG response criteria.
Timepoint [3] 325020 0
Time until progression of disease. Follow-up will continue until all patients remaining on study have been followed up for at least 12 months.
Secondary outcome [4] 325025 0
Composite outcome to estimate the frequency of detection of minimal residual disease (MRD) within bone marrow aspirate samples by flow cytometry (using the Euroflow 8 colour panel) in patients assessed at suspected CR and determine its impact on PFS as per IMWG response criteria.
Timepoint [4] 325025 0
At time of suspected CR until disease progression as per IMWG response criteria.
Secondary outcome [5] 325028 0
Change in global health status, as measured by the patient-reported outcome (PRO) instrument EORTC QLQ-C30
Timepoint [5] 325028 0
At baseline and the end of each treatment cycle.

Eligibility
Key inclusion criteria
1. Male or female patients 18 years or older.

2. 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.

3. 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 form 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, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

Male patients, even if surgically sterilized (ie, status post-vasectomy), must agree to one of the following:
- 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, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)

4. Patients must have a diagnosis of a relapsed/refractory multiple myeloma and have had between 1-3 prior therapies

5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

6. Patients must meet the following clinical laboratory criteria:
- Absolute neutrophil count (ANC) greater than or equal to 1,000/mm3 and platelet count greater than or equal to 75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
- Total bilirubin less than or equal to 1.5 times the upper limit of the normal range (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 times ULN.
- Calculated creatinine clearance greater than or equal to 30 mL/min.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with known thalidomide refractory disease or thalidomide intolerance.

2. Female patients who are lactating or have a positive serum pregnancy test during the screening period.

3. Failure to have fully recovered (ie, less than or equal to Grade 1 toxicity) from the reversible effects of prior chemotherapy.

4. Major surgery within 14 days before enrollment.

5. Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the combination of ixazomib, thalidomide and dexamethasone.

6. Central nervous system involvement with the disease under study (multiple myeloma).

7. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.

8. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure , unstable angina, or myocardial infarction within the past 6 months.

9. Systemic treatment, within 14 days before the first dose of ixazomib, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort.

10. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.

11. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
12. Known allergy/intolerance to any of the study medications, their analogues, or excipients in the various formulations of any agent.

13. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib, thalidomide and/or dexamethasone including difficulty swallowing.

14. Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.

15. Patient has greater than or equal to Grade 2 peripheral neuropathy, or Grade 1 with pain on clinical examination during the screening period.

16. Participation in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial.

17. Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not.

18. Patients who are either contraindicated or unwilling to receive anticoagulation therapy.

19. Patients who are either contraindicated or unwilling to receive anti-viral prophylaxis for prevention of Varicella reactivation.

20. Patients that do not agree to be registered in, and abide by the requirements of the i-access Risk Management Program

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 6011 0
The Alfred - Prahran
Recruitment hospital [2] 9239 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 13436 0
3004 - St Kilda Road Melbourne
Recruitment postcode(s) [2] 17894 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 293889 0
Commercial sector/Industry
Name [1] 293889 0
Takeda Oncology
Address [1] 293889 0
40 Landsdowne Street, Cambridge, MA
Country [1] 293889 0
United States of America
Primary sponsor type
Individual
Name
Professor Andrew Spencer
Address
Alfred Health, Commercial Road, Melbourne, Victoria, 3004
Country
Australia
Secondary sponsor category [1] 292716 0
None
Name [1] 292716 0
Address [1] 292716 0
Country [1] 292716 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295309 0
Alfred Health Human Research Ethics Committee
Ethics committee address [1] 295309 0
Alfred Health, Commercial Road, Melbourne, Victoria
3004
Ethics committee country [1] 295309 0
Australia
Date submitted for ethics approval [1] 295309 0
20/06/2016
Approval date [1] 295309 0
12/12/2016
Ethics approval number [1] 295309 0
HREC/16/Alfred/97

Summary
Brief summary
The primary purpose of this trial is to evaluate the safety and efficacy of a combination of ixazomib, thalidomide and dexamethasone (ITD) for the treatment of multiple myeloma which has progressed despite one to three lines of previous therapy.

Who is it for?
You may be eligible to enroll in this trial if you are aged 18 or over, and have been diagnosed with relapsed/refractory multiple myeloma for which 1-3 prior therapies have been administered.

Study details
All participants enrolled in this trial will receive ITD therapy, which involves taking a specific regime of oral tablets across four 28-day cycles. Participants will be assessed for adverse events and progression and survival outcomes until all patients remaining on study have been followed up for at least 12 months. .

It is hoped that the findings of this study will provide information on whether the addition of ixazomib to thalidomide and dexamethason (TD) therapy is safe and effective for the treatment of relapsed/refractory multiple myeloma.

Individual patients will remain on study until disease progression, unacceptable toxicity or consent withdrawal, whichever occurs first.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 938 938 0 0

Contacts
Principal investigator
Name 66822 0
Prof Andrew Spencer
Address 66822 0
Alfred Health, Commercial Road, Melbourne, Victoria, 3004
Country 66822 0
Australia
Phone 66822 0
+61 3 90763451
Fax 66822 0
+61 3 90762298
Email 66822 0
aspencer@netspace.net.au
Contact person for public queries
Name 66823 0
Ms Nola Kennedy
Address 66823 0
Alfred Health, Commercial Road, Melbourne, Victoria, 3004
Country 66823 0
Australia
Phone 66823 0
+61 3 90762217
Fax 66823 0
+61 3 90765531
Email 66823 0
n.kennedy@alfred.org.au
Contact person for scientific queries
Name 66824 0
Prof Andrew Spencer
Address 66824 0
Alfred Health, Commercial Road, Melbourne, Victoria, 3004
Country 66824 0
Australia
Phone 66824 0
+61 3 90763451
Fax 66824 0
+61 3 90762298
Email 66824 0
aspencer@netspace.net.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary