None listed
Conditions
Brief summary
Multiple Myeloma is a plasma cell malignancy that remains incurable. In multiple myeloma, patients with non-measurable disease, poor kidney function, extramedullary relapse or central nervous system myeloma have not been studied well in clinical trials. We plan to establish a trial to look at these groups (called strata) who previously had limited prospect of enrolment in clinical trials for multiple myeloma. Therefore, this trial aims to assess the effectiveness of the combination treatment (Selinexor, pomalidomide and dexamethasone) in treating multiple myeloma in the specific group of participants described above. Who is it for? You may be eligible for this study if you have been diagnosed with multiple myeloma and have had 1-2 prior lines of treatment. Study details: After undergoing the consent and screening assessments for the Master trial protocol (MM26/Novel Combinations for Orphan Myeloma: The NORM platform master protocol), you may be consented and assigned to this trial (Domain 1 protocol). All participants on this trial will receive Selinexor, pomalidomide and dexamethasone as oral tablets on a 28-day cycle until the participant experiences either unacceptable toxicity or disease progression. Participants will be monitored for adverse effects for the duration of the treatment, as well as the start of every cycle for assessment of their response to treatment through blood, urine and/or bone marrow samples. They will also be assessed for quality of life, through the completion of a questionnaire. It is hoped that this research will determine whether the combination of selinexor, pomalidomide and dexamethasone will be successful in treating patients with Orphan Multiple Myeloma who have had 1 to 2 prior lines of treatment. If this combination treatment is found to be effective, it may be used to improve the health outcomes for future multiple myeloma patients.
Interventions
MM26/D1 is domain 1 of the MM26 NORM Platform trial. This domain will determine the safety and efficacy of Selinexor, Pomalidomide and Dexamethasone in treating patients who have had at least one relapse or refractory multiple myeloma. Participants meeting inclusion for MM26 Master Protocol in Strata A (renal impairment), B (non-measurable disease), C (extramedullary plasmacytoma), or D (CNS myeloma) will be considered for Domain 1, after undergoing separate screening procedures
For participant
MM26/D1 is domain 1 of the MM26 NORM Platform trial. This domain will determine the safety and efficacy of Selinexor, Pomalidomide and Dexamethasone in treating patients who have had at least one relapse or refractory multiple myeloma. Participants meeting inclusion for MM26 Master Protocol in Strata A (renal impairment), B (non-measurable disease), C (extramedullary plasmacytoma), or D (CNS myeloma) will be considered for Domain 1, after undergoing separate screening procedures For participants with renal impairment (Strata A) the study will be conducted in two stages. Stage 1: A safety run-in stage will confirm the planned optimal dose schedule for these participants. Up to 10 participants will be enrolled in a lead-in safety phase and monitored by the Trial Monitoring Committee (TMC) for treatment related toxicities. If the initial dose level of Pomalidomide and Selinexor is deemed intolerable, other dose levels will be explored. Decisions to escalate or de-escalate the dose and the identification of the optimal dose will be guided by use of a dual-criteria Bayesian proof-of-concept approach. If more than 3 of the first 10 evaluable participants have grade 4 related non-haematological toxicity, then the causative agent (pomalidomide or Selinexor) will be determined by the TMC, and a dose reduction instituted as per dose levels described below. Each treatment cycle will be 28 days for the first two cycles only. The dose de-escalation schedule for Strata A is as follows: Level 1 (starting dose): Pomalidomide 4mg (oral) – Daily for days 1 to 21 Selinexor 60mg (oral) - weekly Level 2: Pomalidomide 3mg (oral) Daily for days 1 to 21 Selinexor 40mg (oral) - weekly Level 3: Pomalidomide 2mg (oral) Daily for days 1 to 21. Selinexor 20mg (oral) - weekly Stage 2: Provided that no more than 3 participants in the first 10 evaluable participants develop grade 4 treatment-related toxicities, the stratum will proceed to the expansion phase. Participants proceeding to the expansion phase will continue with treatment at the recommended dose determined in the lead-in phase. Expansion phase continues until the participant withdraws from disease progression or unacceptable toxicity. For all other participants from Strata B (Non-measurable disease), Strata C (Extramedullary plasmacytomas) and Strata D (CNS involvement) the following study treatment will be assigned in a 28-day cycle: Selinexor 60mg (oral) weekly Pomalidomide 4mg on days 1 to 21 (oral) Dexamethasone 40mg (oral) weekly (20mg if greater than 75 years old). All participants enrolled to Domain 1 will continue study medication unless they develop disease progression, unacceptable treatment related toxicities, withdraw consent or are loss to follow-up. Compliance will be monitored via drug accountability exercises completed by the participating site and the sponsor.
Sponsors
Australasian Leukaemia & Lymphoma Group
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligibility criteria specific to Treatment Specific Appendix - Selinexor, Pomalidomide, Dexamethasone (SPd) include: 1.Previous bortezomib therapy and either: failure to achieve at least a partial response (PR) during treatment OR progressive disease (PD) during treatment or within 6 months of discontinuing treatment OR contraindication or experienced an intolerance to treatment with bortezomib AND 2.Previous lenalidomide therapy and either: treatment failure with lenalidomide, as confirmed by progressive disease during treatment within 6 months of discontinuing lenalidomide OR a contraindication or intolerance to treatment with lenalidomide. 3.Must agree to contraceptive requirements
Exclusion criteria
See ALLG MM26/NORM: Novel Combinations for Orphan Myeloma: The NORM platform study Master Protocol for eligibility criteria relevant to all domain protocols. Exclusion criteria specific to Treatment Specific Appendix - Selinexor, Pomalidomide, Dexamethasone (SPd) include: 1.Previous treatment with pomalidomide or Selinexor 2.Contraindication to pomalidomide, Selinexor or dexamethasone 3.Active gastrointestinal dysfunction that prevents the patient from swallowing tablets or interferes with absorption of trial treatments.
Outcome results
None listed