Multiple myeloma Cancer Multiple myeloma
Conditions
Interventions
Participants are randomised in a 1:1 ratio to receive 2 cycles ITD.
ITD re-induction therapy
All participants will be registered at trial entry and will receive re-induction therapy with 4-6 cycles o
Sponsors
University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosed with relapsed MM (with measurable disease, according to IMWG criteria) previously treated with ASCT 2. First Progressive Disease (PD) at least 12 months following first ASCT, requiring therapy 3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 4. Aged at least 18 years 5. Participants must have the following blood results within 14 days before registration: a. Absolute neutrophil count (ANC) =1x109/L b.Platelet count =75x109/L. If the participant has =50% bone marrow infiltration a platelet count of =50x109/L is allowed. Platelet transfusions are not allowed within 3 days before registration in order to meet these values. 6. Adequate renal function within 14 days before registration: a.Creatinine clearance =30ml/min (calculated according to Cockcroft-Gault equation or other locally approved formula) 7. Adequate hepatobiliary function within 14 days before registration: a. Total bilirubin <2 x upper limit of normal (ULN) b. ALT <2 x ULN 8. Adequate pulmonary function within 14 days before registration: a. Adequate respiratory functional reserve (delineated by KCO/DLCO (carbon monoxide diffusion in the lung) of =50%). No evidence of a history of pulmonary disease. If a significant history, then a review by a respiratory medicine physician is required 9. Adequate cardiac function within 12 weeks before registration: a. Left ventricular ejection fraction (LVEF) =40%. Note: repeat confirmation of cardiac function is needed if treatment is given between this assessment and registration 10. Female participants who: 10.1. Are not of childbearing potential (Appendix 8), OR 10.2. 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 until 90 days after the last dose of study drug, OR 10.3. 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 participants, even if surgically sterilised (i.e. status post-vasectomy), must agree to one of the following: a. Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR b. 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.) Contraception for female and male participants must be in accordance with (and consent to) the Celgene-approved Thalidomide Pregnancy Prevention Programme 11. If female and of childbearing potential (see Appendix 8), must have a negative pregnancy test performed by a healthcare professional in accordance with the Celgene Thalidomide Pregnancy Prevention Programme 12. Patients agree not to receive other clinical trials treatment, including investigational medicinal products (IMPs) not included in this trial, within 30 days of trial registration and throughout the duration of the trial, until disease progression 13. Able to provide written informed consent
Exclusion criteria
Exclusion criteria: 1. Received prior second line therapy for their relapsed disease other than local radiotherapy, therapeutic plasma exchange, or dexamethasone (up to a maximum of 200mg is allowed but not within 30 days prior to registration). Radiotherapy sufficient to alleviate or control pain of local invasion is permitted, but must not be within 14 days before registration. Patients who have received hemi-body radiation or similar since relapse will not be eligible 2. =Grade 2 peripheral neuropathy within 14 days before registration 3. Known HIV or Hepatitis B/C seropositivity 4. Known resistance, intolerance or sensitivity to any component of the planned therapies 5. Any medical or psychiatric condition which, in the opinion of the investigator, contraindicates the participant’s participation in this study 6.Previous or concurrent malignancies at other sites (excluding completely resected non-melanoma skin cancer or carcinoma in situ of any type, such as cervical cancer) 7. Pregnant, lactating or breast feeding female participants 8. Failure to have fully recovered (i.e. less than or equal to Grade 1 toxicity) from the reversible effects of prior chemotherapy. 9. Major surgery within 14 days before registration 10. Central nervous system involvement with myeloma 11. Ongoing or active infection requiring systemic antibiotic therapy or other serious infection within 14 days before registration 12. 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 13. Systemic treatment, within 14 days before the first dose of ixazomib with strong CYP3A inducers (e.g. rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort 14. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib, including difficulty swallowing 15. Patients that have previously been treated with ixazomib or participated in a study with ixazomib whether treated with ixazomib or not
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| All outcome measures are measured at baseline, the end of each re-induction cycle, the end of re-induction, 100 days post-ASCT, the end of consolidation, 8 weeks post-randomisation 2, 3 monthly post randomisation-2 until disease progression and at the time of disease progression: 1. Overall response rate following ASCT, defined as the impact on Depth of Response (DoR: <VGPR vs. =VGPR) when salvage ASCT conditioning is augmented by the addition of a proteasome inhibitor, will be determined according to the IMWG Uniform Response Criteria for Multiple Myeloma 2. Progression-free survival, is defined as the time from randomisation to the consolidation part of the trial to first documented evidence of disease progression or death from any cause. Participants who do not progress will be censored at the last date they were known to be alive and progression free | — |
Secondary
| Measure | Time frame |
|---|---|
| All outcome measures are measured at baseline, the end of each re-induction cycle, the end of re-induction, 100 days post-ASCT, the end of consolidation, 8 weeks post-randomisation 2, 3 monthly post randomisation-2 until disease progression and at the time of disease progression: 1. Overall survival is defined as the time from randomisation to the consolidation/ maintenance part of the trial post-ASCT to death from any cause or last follow-up 2. Time to disease progression is defined as time from randomisation to the consolidation/ maintenance part of the trial post-ASCT to first documented evidence of disease progression. Participants who die without disease progression will be censored in the analysis. 3. Overall response rate following re-induction will be determined according to the IMWG Uniform Response Criteria for Multiple Myeloma 4. Progression-free survival 2 is defined as the time from second randomisation to the consolidation/maintenance part of the trial post-ASCT to second documented disease progression (or the start of next line anti-myeloma treatment), or death from any cause, whichever occurs first. Participants alive and for whom a second progression after second randomisation has not been observed will be censored at the last day they were known to be alive and second progression-free. 5. Time to next line treatment is defined as the time from the date of randomisation to the date of commencement of next line treatment. Participants who do not receive next line treatment will be censored at the date of the last assessment or follow-up visit where they are known to have received no new therapy. 6. Duration of response to protocol treatment is defined from the time of achieving at least a partial response to the date of first documented evidence of disease progression. Participants who die prior to documentation of disease progression will be censored at the date of death. Participants dying from causes not primarily due to progression will also be | — |
Countries
England, Northern Ireland, Scotland, United Kingdom
Outcome results
None listed