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.
- Conditions
- Multiple MyelomaCancer - Myeloma
- Registration Number
- ACTRN12616000894493
- Lead Sponsor
- Professor Andrew Spencer
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 40
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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.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.
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
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To investigate the efficacy of ITD combination therapy in relapsed/refractory multiple myeloma patients as assessed using International Myeloma Working Group(IMWG) response criteria.[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.];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[At the end of each cycle for the duration of treatment.]
- Secondary Outcome Measures
Name Time Method