None listed
Conditions
Brief summary
Australian data shows that 20-25% of newly diagnosed myeloma patients who are treated with standard of care relapse within the first 12 months of starting treatment and their survival rate is lower than that of patients who relapse after 12 months of starting treatment. This group of patients are deemed to be at ‘high-risk’. The purpose of this study is to optimise treatment of newly diagnosed multiple myeloma (MM) patients who undergo autologous stem cell treatment (ASCT) by using diagnostic techniques to guide whether selinexor should be added to standard care, whether it is and beneficial to do so. Who is it for? You may be eligible for this study if you are aged 18 or older, you have been recently diagnosed with multiple myeloma. If must meet additional heart, liver and kidney health criteria prior to commencing treatment. [Study details] All participants who choose to enrol in this study will have a bone marrow sample taken and assessed to determine whether they are at high risk or standard risk disease. These details will then be used to allocate participants for ‘induction’ therapy, to either standard of care treatment (consisting of bortezomib, lenalidomide and dexamethasone), or standard of care treatment with added selinexor. This is a risk-adaptive approach to treatment, meaning your treatment is guided by the results of your myeloma risk profile. Participants will continue with their allocated treatments for 4-5 months. After this time, all participants will then undergo preparation for an autologous stem cell transplant, where healthy stem cells will be harvested from each participant and expanded externally, before being re-implanted back to stimulate further stem cell growth. At 5-6 months after the transplant, all participants will be required to provide a second bone marrow sample to undergo a second test to check how they are responding to treatment and assess if there is a very small but detectable number of myeloma cells. For standard risk patients, if there isn’t any detectable myeloma cells, you will continue treatment with only lenalidomide. If there are detectable cells, you will be given lenalidomide and selinexor. High-risk patients will be given lenalidomide and selinexor regardless of the results. This is called 'maintenance' therapy. Participants will then continue taking their second allocation of medications for maintenance for until the treatments are no longer effective. This could range from months to years. Further bone marrow samples will be required at 6 and 12 months after commencing maintenance treatment to test for detectable myeloma cells. The trial is intended to run over 4-5 years. You will be asked to complete short questionnaires about your multiple myeloma treatment and your health-related quality of life every month prior to the transplant, about 4-5 months after transplant and within 12 months after commencing maintenance therapy.
Interventions
A. [RISK STRATIFICATION WITH SKY92 MM PROFILER]
Patients will be risk-stratified to either standard risk or high risk using the MM profiler with SKY92 algorithm - Partipicants will have a sample of their bone marrow taken for this test about 1 week before Day 1 of the first treatment cycle.
1. [HIGH RISK (HR) group]
1.1 - INDUCTION (4 cycles)
- 35-day cycle
- Bortezomib 1.3mg/m^2, as intravenous or subcutaneous injection, on days 1, 8, 15 and 22.
- Lenalidomide 25mg orally once daily on days 1
A. [RISK STRATIFICATION WITH SKY92 MM PROFILER] Patients will be risk-stratified to either standard risk or high risk using the MM profiler with SKY92 algorithm - Partipicants will have a sample of their bone marrow taken for this test about 1 week before Day 1 of the first treatment cycle. 1. [HIGH RISK (HR) group] 1.1 - INDUCTION (4 cycles) - 35-day cycle - Bortezomib 1.3mg/m^2, as intravenous or subcutaneous injection, on days 1, 8, 15 and 22. - Lenalidomide 25mg orally once daily on days 1 – 21. - Dexamethasone 40mg orally on days 1, 8, 15 and 22. - Selinexor 40mg orally on days 1, 8, 15 and 22 of each cycle. 1.2 AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT) - Melphalan 200mg/m^2 intravenous infusion day -1; minimum of 2 x 10^6 CD34 peripheral blood stem cells for re-infusion day 0. Stem cell harvesting as per standard of care, after 2 cycles of induction. 1.3 HIGH RISK (HR) – CONSOLIDATION (2 cycles) - 90-100 days after ASCT - 35-day cycle - Bortezomib 1.3mg/m^2, as intravenous or subcutaneous injection, on days 1, 8, 15 and 22. - Lenalidomide 25mg orally once daily on days 1 – 21. - Dexamethasone 40mg orally on days 1, 8, 15 and 22. - Selinexor 40mg orally on days 1, 8, 15 and 22 of each cycle. 2. [STANDARD RISK (SR) group] 2.1 - INDUCTION (4 cycles) - 28-days cycle - Bortezomib 1.3mg/m^2, as intravenous or subcutaneous injection, days 1, 8, 15 and 22. - Lenalidomide 25mg orally once daily on days 1 – 21. - Dexamethasone 40mg orally on days 1, 8, 15 and 22. 2.2 AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT) - Melphalan 200mg/m^2 intravenous infusion day -1; minimum of 2 x 10^6 CD34 peripheral blood stem cells for re-infusion day 0. Stem cell harvesting as per standard of care, after 2 cycles of induction. 2.3 STANDARD RISK (SR) – CONSOLIDATION (2 cycles) - 90-100 days after ASCT - 28-days duration - Bortezomib 1.3mg/m^2, as intravenous or subcutaneous injection, days 1, 8, 15 and 22. - Lenalidomide 25mg orally once daily on days 1 – 21. - Dexamethasone 40mg orally on days 1, 8, 15 and 22. B. [RESPONSE ADAPTATION WITH EUROFLOW] Patients will then undergo EuroFlow testing to determine is there is any minimal resiudal disease (this means if there is a very small but detectable amount of myeloma cells). Partipicants will have a sample of their bone marrow taken for this test about 6 to 8 weeks after consolidation treatment finishes. Maintenance treatment will commence as soon as possible after the EuroFlow test becomes available: 1. [STANDARD RISK (SR) with minimal resiudal disease negative group] - 28-day cycle. - Lenalidomide 10mg orally every day continuously. Increasing to 15mg orally after 3 cycles if tolerated. - Treatment will continue until disease progression or unacceptable toxicity 2. [HIGH RISK (HR) or STANDARD RISK (SR) with minimal resiudal disease positive group]): - 28-day cycle. - Lenalidomide 10mg orally every day continuously. Increasing to 15mg orally after 3 cycles if tolerated. - Selinexor 40mg orally 1 day per week continuously - Treatment will continue until disease progression or unacceptable toxicity Any unused medication (e.g: capsules taken home) will need to be returned to the clinic at every clinic visit
Sponsors
Australasian Myeloma Research Consortium
Study design
Allocation
Non-randomised 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
1. Male and Female patients, 18 years of age or older 2. Able to provide written consent. 3. Newly diagnosed MM as per IMWG criteria eligible for ASCT. 4. Diagnostic bone marrow sample available for SKY92 risk analysis. 5. Measurable disease as defined by any of the following o Serum M-component >5 g/L, and/or o Urine M-component > 200 mg/24 h, and/or o Involved serum FLC level >100mg/L. 6. No contraindication to the use of any of the study drugs and able to comply with trial requirements. 7. Adequate liver function (total bilirubin < 2.0x ULN, ALT < 5.0x ULN) unless considered secondary to MM. 8. Absolute neutrophil count >= 1.0 x 109/L. 9. Platelet count >= 50 x 109/L (>= 30 x 109/L if MM involvement in the marrow is greater than 50%), patients should not have received platelet transfusions within 7 days of the screening platelet count. 10. Hb >= 80g/L, red cell transfusions as per institutional protocol are allowed. 11. Woman of childbearing potential must agree to ongoing pregnancy testing, to be performed within 72 hours before during treatment and on day 28 after last dose of study treatment. 12. Women of childbearing potential must agree to use one highly effective method and preferably one additional effective (barrier) method during the study and for 28 days following the last dose of study treatment. 13. Male participants who are sexually active with WOCBP must use a condom during sexual contact during study and for at least 7 days after last dose of study treatment. 14. Male participants must not donate sperm during study and for at least 7 days after last dose of study treatment.
Exclusion criteria
1. Patients who have had myocardial infarction within 6 months prior to enrolment, or New York Hospital Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. 2. Any other serious or uncontrolled medical or psychiatric illness that could, in the investigators’ opinion, potentially interfere with the completion of treatment according to this protocol. 3. Known ongoing or active systemic infection, active hepatitis B or C infection, or known human immunodeficiency positivity. 4. Women who are pregnant or lactating. Women of child-bearing potential must have a negative urine pregnancy test at Screening. 5. Any patient who is unable or unwilling to meet the requirements of the lenalidomide pregnancy prevention programme. 6. Active malignancy with the exception of any of the following: o Adequately treated basal cell carcinoma, squamous cell carcinoma or in situ cervical cancer. o Adequately treated stage 1 cancer from which the subject is currently in remission from and has been in remission for > 2 years. o Stage 1 prostate cancer that does not require treatment. o Any other cancer from which the subject has been disease-free for > 2 years. 7. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
Outcome results
None listed