Cyclophosphamide and dexamethasone in combination with Ixazomib, in relapsed or refractory multiple myeloma (RRMM) patients who have relapsed after treatment with thalidomide, lenolidomide and bortezomib.
- Conditions
- Topic: CancerSubtopic: Haematological OncologyDisease: MyelomaCancer
- Registration Number
- ISRCTN58227268
- Lead Sponsor
- niversity of Leeds
- Brief Summary
2020 Protocol article in https://pubmed.ncbi.nlm.nih.gov/33008427/ protocol (added 07/10/2020) 2022 Results article in https://pubmed.ncbi.nlm.nih.gov/35365598/ (added 04/04/2022) 2022 Abstract results in https://doi.org/10.1097/01.hs9.0000829488.58829.9f P11 (added 12/09/2023) 2022 Poster results in https://doi.org/10.1097/01.hs9.0000829616.80742.a1 (added 12/09/2023)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 112
1. Able to give informed consent and willing to follow study protocol assessments
2. Aged 18 years or over
3. Participants with confirmed MM based on IMWG criteria, 2009
4. Measurable disease with at least one of the following:
4.1. Paraprotein >5g/L or 0.5 g/l for IgD subtype;
4.2. Serum-free light chains >100mg/L with abnormal radio for light chain only myeloma;
4.3. Bence Jones protein >200mg/L
5. Participants with relapsed or relapsed refractory myeloma and now require further treatment following exposure to thalidomide, lenalidomide and bortezomib regardless of response to these
6. ECOG Performance Status = 2
7. Required laboratory values within 14 days prior to Randomisation:
7.1. Platelet count =50x109/L. Platelet count of 3050 is acceptable if bone marrow aspirate shows tumour replacement of >50%. Platelet support is permitted within 14 days prior to randomisation although platelet transfusions to help patients meet eligibility criteria are not allowed within 72 hours prior to the blood sample to confirm protocol eligibility
7.2. Absolute neutrophil count =1.0 x 109/L. Growth factor support is not permitted within 14 days prior to randomisation
7.3. Haemoglobin > 9 g/dL. Blood support is permitted
7.4. ALT and / or AST =3 x upper limit of normal
7.5. Creatinine clearance = 30 ml/min (using Cockcroft Gault formula)
7.6. Bilirubin =1.5 x upper limit of normal
8. Female participants should avoid becoming pregnant and male participants should avoid impregnating a female partner. Both nonsterilised and sterilised females and males of reproductive age should use effective methods of contraception during the entire trial treatment (including treatment breaks) and up to 90 days after the last dose of trial treatment
9. Post-allograft patients may be included if >12 months from transplant
1.Those with nonmeasurable disease, a solitary bone or solitary extramedullary plasmacytoma, Plasma cell leukaemia
2. Prior malignancy other than those treated with surgery.
3. Participants with a known or underlying uncontrolled concurrent illness that, in the investigators opinion, would make the administration of the study drug hazardous or circumstances that could limit compliance with the study, including, but not limited to the following: acute or chronic graft versus host disease, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within past 6 months, uncontrolled cardiac arrhythmia, renal failure, psychiatric or social conditions that may interfere with participant compliance, or any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the participant at unacceptable risk for adverse outcome if he/she were to participate in the study.
4. Patients who have previously received Ixazomib or MLN9708 in a trial. Previous experimental agents or approved anti-tumour treatment within 30 days before the date of randomisation.
5. A maximum of 160mg of dexamethasone (in 40mg blocks) may be given between screening and the beginning of treatment if medically required but should be stopped before trial treatment starts. Bisphosphonates for bone disease and radiotherapy for palliative intent are also permitted.
6. Participants with a history of a refractory nausea, diarrhoea, vomiting, malabsorption, gastrointestinal surgery or other procedures that might, in the opinion of the Investigator, interfere with the absorption or swallowing of the study drug(s)
7. Peripheral neuropathy of = grade 2 (or grade 1 with pain) severity (as per NCICTCAEv4.0)
8. Gastrointestinal disorders that may interfere with absorption of the study drug
9. Active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B or C) hepatitis
10. Female patients who are lactating or have a positive pregnancy test during the screening period
11. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
12. Systemic treatment, within 14 days before the first dose of Ixazomib, 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
13. Major surgery within 14 days prior to the date of randomisation
14. Radiotherapy within 7 days for palliative pain control or therapeutic radiotherapy within 14 days prior to randomisation
15. Myeloma involving the Central Nervous System
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method