None listed
Conditions
Brief summary
The purpose of this study to determine whether the addition of selinexor to lenalidomide maintenance therapy post Autologous Stem Cell Transplant for multiple Myeloma patients increases the proportion of patients who are progression free 3 years post randomisation. Who is it for? You may be eligible for this study if you are an adult who has been newly diagnosed with Multiple Myeloma and are eligible for an Autologous Stem Cell Transplant. Study details Participants in this study will be randomised to receive either: Lenalidomide 10mg,orally,once a day for 21 days or Lenalidomide 10mg,orally,once a day for 21 days with Selinexor 40mg,orally, weekly Lenalidomide may be increased to 15mg orally, once a day for 21 days from cycle 4 onwards, provided good tolerance and no lenalidomide-related greater than or equal to grade 3 adverse events. Selinexor may be maintained at 40mg orally, weekly from cycle 2 onwards provided good tolerance and no selinexor-related greater than or equal to grade 3 adverse events Each cycle lasts 28 days, Patients will receive treatment until disease progression. During the trial patients will have blood tests performed and bone marrow samples taken to help determined the progress of the treatment. It is hoped that this research will help determine whether this treatment prolongs the progression free survival for patients, and what kinds of side effects/complications may occur with this treatment.
Interventions
This trial is for newly diagnosed Multiple Myeloma patients who are eligible for an Autologous Stem Cell Transplant (ASCT). This trial looks at whether the addition of the drug Selinexor to the routine treatment after the transplant prolongs progression free survival and overall survival.
Registered patients who have undergone ASCT and are still eligible for the trial will be randomised no later than 115 days post ASCT.
Patients are randomised to either receive
Lenalidomide 10mg, orally once a
This trial is for newly diagnosed Multiple Myeloma patients who are eligible for an Autologous Stem Cell Transplant (ASCT). This trial looks at whether the addition of the drug Selinexor to the routine treatment after the transplant prolongs progression free survival and overall survival. Registered patients who have undergone ASCT and are still eligible for the trial will be randomised no later than 115 days post ASCT. Patients are randomised to either receive Lenalidomide 10mg, orally once a day for 21 days or Lenalidomide 10mg, orally once a day for 21 days with Selinexor 40mg orally weekly. If well tolerated, after the first cycle the target dose of Selinexor will be maintained at 40mg, orally, weekly. No dose escalation of Selinexor beyond 40mg/week is permitted. If well tolerated, after the 4th cycle Lenalidomide can be increased to 15mg, orally, daily for 21 days. Each cycle is 28 days. Patients will receive treatment until disease progression. The clinical trial team will monitor drug returns from the patient and will issue a diary if applicable.
Sponsors
Australian Leukeamia and Lymphoma Group (ALLG)
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Patient must be 18 years of age or older • Patient has voluntarily agreed and has given written consent to both the main study and correlative study • Diagnosis of MM as per IMWG guidelines (Appendix 3) • Must be eligible for front-line melphalan conditioned ASCT • Will have undergone at least 3-6 cycles of up-front therapy containing a proteasome inhibitor (PI) and/or immunomodulatory drug (IMID) and ASCT (tandem transplants allowable) prior to screening procedures (note consent and registration will occur prior to ASCT • Pre-ASCT (preferably prior to and if not, as early as possible during induction therapy) bone marrow aspirate trephine for correlative studies. Patients who are unable to provide pre ASCT BMAT samples for correlative studies can be enrolled into the study if a waiver is granted from the coordinating principal investigator • Measurable disease at diagnosis: • Serum M-protein greater than or equal to 5 g/L, or • Urine M-protein greater than or equal to 200 mg/24 hour, or • In patients without measurable serum or M-protein, serum free light chain (SFLC) greater than 100mg/L (involved light chain) and an abnormal serum k/l ratio or • In IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) greater than or equal to 7500 mg/L (7.5 g/L). • Female patients who are postmenopausal for at least 1 year prior to screening visit OR surgically sterile OR agree to practice 2 effective methods of contraception at the same time from 4 weeks before start of study treatment and until 90 days after the last dose of study drugs OR agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. • Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 (Appendix 2). • Subjects must agree not to donate blood, semen or sperm while on study and at least 90 days after treatment discontinuation. • Subjects must agree not to share their medication and to return unused supplies. • Patients must meet the following clinical laboratory criteria: o Absolute neutrophil count (ANC) greater than or equal to 1.5x10^9/L and platelet count greater than or equal to 100 x10^9/L. Platelet transfusions to help patients meet eligibility criteria are not allowed. o Total bilirubin less than or equal to 1.5 x the upper limit of the normal range (ULN) o Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 x ULN. o Calculated creatinine clearance greater than or equal to 30 mL/min per Cockcroft-Gault equation.
Exclusion criteria
• Pregnant or lactating women. • Failure to have fully recovered (i.e. less than or equal to Grade 1 toxicity) from the reversible effects of prior chemotherapy. • Progressive disease post-ASCT. • Major surgery within 14 days before enrolment. • Radiotherapy within 14 days before enrolment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the selinexor. • Central nervous system involvement. • Active infection requiring iv antibiotics in 5 days prior to starting study therapy. • Subjects with active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 IU/ml prior to first dose of trial treatment. Subjects with untreated hepatitis C virus (HCV) are not allowed. Subjects with Human Immunodeficiency Virus (HIV) who have CD4+ T-cell counts greater than or equal to 350 cells/µL and no history of AIDS-defining opportunistic infections in the last year are allowed. • Any serious medical or psychiatric condition (including uncontrolled infection) that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol or would be a contraindication to consolidation/maintenance therapy. • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent. • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of study medications including difficulty swallowing. • Patient has greater than or equal to 2 grade peripheral neuropathy or grade 1 with pain on clinical examination during the screening period. • Participating in other clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial. • Contraindication to the use of either lenalidomide or selinexor.
Outcome results
None listed