A randomised phase II trial of selinexor with cyclophosphamide and prednisolone in relapsed or refractory multiple myeloma (RRMM) patients

INTERVENTION: The trial is designed as a randomised, controlled, open, parallel group, multicentre phase II trial to evaluate the clinical efficacy of selinexor in combination with cyclophosphamide and prednisolone. A calibration group will receive cyclophosphamide plus prednisolone alone, and will be used to evaluate the validity of the outcome in the experimental group. Participants will be randomised on a 3:1 basis to receive either selinexor + cyclophosphamide + prednisolone (SCP) or cyclophosphamide + prednisolone (CP). A maximum of 60 participants will be recruited (45 participants in the SCP arm, and 15 participants in the CP arm). Participants who experience disease progression on the CP arm may receive SCP, once progression has been confirmed by the CTRU and the participant has been deemed eligible to receive SCP. Patients randomised to SCP have no further trial treatment stipulated following SCP therapy. The analysis of the treatment switch phase of the trial is exploratory. SCP combination Selinexor oral 100mg once a week – days 1 , 8 , 15 & 22 Cyclophosphamide oral 50mg once daily, starting on day 1 Prednisolone oral 30mg every other day, starting on day 1 CP combination Cyclophosphamide oral 50mg once daily, starting on day 1 Prednisolone oral 30mg every other day, starting on day 1 Followed by SCP Combination Selinexor oral 100mg once a week – days 1, 8, 15 & 22 Cyclophosphamide oral 50mg (or dose given previously) once daily, starting on day 1 Prednisolone oral 30mg (or dose given previously) every other day, starting on day 1 The final analysis will take place after all patients have been followed up for at least 6 months or have progressed on the first phase of treatment (whichever is sooner). Further analyses relating to the treatment switch phase of the trial will take place after all patients have been followed up for at least 6 months or have progressed (whichever is sooner). CONDITION: Specialty: Cancer, Primary sub‐specialty: Haematological Oncology; UKCRC code/ Disease: Cancer/ Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissu ; Cancer PRIMARY OUTCOME: Progression free survival at 6 months SECONDARY OUTCOME: 1. Safety and toxicity, via adverse reactions and adverse events from consent until 28 days post last dose of trial treatment ; 2. Progression‐free survival at 6 months or until disease progression, monitored via blood results; 3. Maximum response, monitored via blood results throughout the trial; 4. Time to maximum response, monitored via blood results throughout the trial; 5. Duration of response, monitored via blood results throughout the trial; 6. Compliance to therapy, measured at all stages of the trial INCLUSION CRITERIA: 1. Able to give informed consent and willing to follow all trial protocol assessments 2. Aged 18 years or over 3. Participants with confirmed myeloma based on International Myeloma Working Group (IMWG) criteria 4. Measurable disease with at least one of the following: 4.1. Paraprotein =5g/L 4.2. Serum free light chains =100mg/L with abnormal ratio for light chain only myeloma 4.3. Bence Jones protein =200mg/24h 5. Participants with relapsed or relapsed refractory myeloma who have received = 2 prior anti‐myeloma treatments including a proteasome inhibitor and lenalidomide, and now require further treatment 6. Patients for which cyclophosphamide and prednisolone alone would be a suitable treatment 7. Eastern Cooperative Oncology Group (ECOG) performance status of = 2 8. Female participants of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception,