None listed
Conditions
Brief summary
PURPOSE The primary purpose of this study is to determine the efficacy and safety of the addition of ixazomib and low dose dexamethasone maintenance therapy for transplant-eligible multiple myeloma (MM) patients who are undergoing single autologous stem cell transplantation (ASCT) as part of front-line therapy. WHO IS IT FOR? You may be eligible to join this study if you are aged over 18 years, have been diagnosed with symptomatic MM as per International Myeloma Working Group (IMWG) criteria, are eligible for front-line melphalan conditioned autologous stem cell transplant (ASCT), and do not have central nervous system involvement with the disease (MM). STUDY DETAILS Enrolled participants who have achieved clinical and haematological recovery following ASCT will undergo screening for study eligibility no earlier than 75 days following ASCT, complete screening within 15 days, and be randomised into treatment arms no later than 115 days after ASCT. Participants will then be randomised 1:1 to the control arm (thalidomide + dexamethasone), or the experimental arm (thalidomide + dexamethasone + ixazomib), for a maximum of 12 months or until the disease progresses, whichever occurs first. Outcomes It is hoped that the findings of this trial will provide information on: 1. Whether the addition of ixazomib to standard maintenance therapy will improve progression free survival in multiple myeloma patients who have undergone ASCT as part of front-line therapy; and 2. Provide information on the safety and efficacy of ixazomib addition to standard maintenance therapy.
Interventions
This is a randomised, multi-centre, open label phase 3 trial, with the primary objective to determine whether the addition of ixazomib to thalidomide and low dose dexamethasone maintenance therapy post-ASCT for MM patients improves progression free survival (PFS) and/or overall survival (OS).
Patients with symptomatic MM who are transplant eligibile will be registered prior to undergoing ASCT. Patients who have achieved clinical and haematologic recovery following ASCT will initiate screening
This is a randomised, multi-centre, open label phase 3 trial, with the primary objective to determine whether the addition of ixazomib to thalidomide and low dose dexamethasone maintenance therapy post-ASCT for MM patients improves progression free survival (PFS) and/or overall survival (OS). Patients with symptomatic MM who are transplant eligibile will be registered prior to undergoing ASCT. Patients who have achieved clinical and haematologic recovery following ASCT will initiate screening for study eligibility no earlier than 75 days following ASCT, complete screening within 15 days, and be randomised no later than 115 days after ASCT. Patients are randomised 1:1 to receive either: Arm 1 (Control)- 12 cycles of thalidomide (100mg/day- oral tablet), dexamethasone (40mg/week- oral tablet); or Arm 2 (Experimental): 12 cycles of thalidomide (100mg/day- oral tablet), dexamethasone (40mg/week-oral tablet), plus ixazomib therapy (4mg, on day 1, day 8, and day15 of each cycle- oral capsule); for a maximum of 12 months. A treatment cycle is defined as 28 days. Cycle 13 is the time-point at the end of consolidation treatment (cycles 1-12) The study drugs will be administered or dispensed only to eligible patients under the supervision of the investigator or identified sub-investigator(s). The appropriate study personnel will maintain records of study drug receipt and dispensing.
Sponsors
Australasian Leukaemia and Lymphoma Group (ALLG)
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each patient must meet all of the following inclusion criteria to be enrolled in the study: 1. Male or female patients 18 years or older. 2. Voluntary written informed 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. Patients must have a diagnosis of a symptomatic MM as per IMWG criteria and be eligible for front-line melphalan conditioned ASCT, with > 2x 10^6 CD34/Kg available for ASCT. 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 4 weeks before the start of study treatment and during the entire study treatment period and through 90 days after the last dose of the study drugs, OR - Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception). Male patients, even if surgically sterilized (i.e., 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 (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception). 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) >= 1,000/mm^3 and platelet count >= 75,000/mm^3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment. - Total bilirubin <= 1.5 x the upper limit of the normal range (ULN). - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3 x ULN. - Calculated creatinine clearance >= 30 mL/min per Cockcroft-Gault equation.
Exclusion criteria
Patients meeting any of the following exclusion criteria are not to be enrolled in the study: 1. Female patients who are lactating or have a positive serum pregnancy test during the screening period. 2. Failure to have fully recovered (i.e., <= Grade 1 toxicity) from the reversible effects of prior chemotherapy. 3. Progressive disease post-ASCT 4. Failure of haemopoietic recovery post-ASCT 5. Major surgery within 14 days before enrolment. 6. Radiotherapy within 14 days before enrolment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib. 7. Central nervous system involvement with the disease under study (myeloma). 8. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrolment. 9. 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. 10. 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. 11. Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. 12. Any serious medical or psychiatric condition (including uncontrolled infection) that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol or would be a contraindication to consolidation/maintenance therapy 13. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. 14. Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing. 15. Diagnosed or treated for another malignancy within 2 years before study enrolment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 16. Patient has >= Grade 2 peripheral neuropathy, or Grade 1 with pain on clinical examination during the screening period. 17. 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. 18. Contraindication to the use of either thalidomide, ixazomib or dexamethasone
Outcome results
None listed