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Trial registered on ANZCTR


Registration number
ACTRN12620000291987p
Ethics application status
Not yet submitted
Date submitted
20/02/2020
Date registered
4/03/2020
Date last updated
4/03/2020
Date data sharing statement initially provided
4/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
An ALLG Trial to compare the use of Selinexor, Lenalidomide and Dexamethasone with Lenalidomide alone for patients with newly diagnosed Multiple Myeloma undergoing Autologous stem cell transplant.
Scientific title
MM23- An ALLG phase 3 randomised trial of Selinexor and Lenalidomide-dexamethasone versus lenalidomide maintenance post Autologous stem cell transplant for patients with Newly Diagnosed multiple myeloma.
Secondary ID [1] 300571 0
ALLG MM23
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 316303 0
Condition category
Condition code
Cancer 314571 314571 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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 and dexamethasone 20mg, orally weekly.
If well tolerated, after the first cycle Selinexor can be increased to 60mg, orally, weekly.
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.
Intervention code [1] 316876 0
Treatment: Drugs
Comparator / control treatment
.Patients who are randomised to the comparator arm will receive Lenalidomide 10mg, orally once a day for 21 days.
If well tolerated, after the 4th cycle Lenalidomide can be increased to 15mg, orally, daily for 21 days.
Patients will receive treatment until disease progression.
Control group
Active

Outcomes
Primary outcome [1] 322901 0
The primary outcome will be to determine whether the addition of selinexor-dexamethasone to lenalidomide maintenance therapy post Autologous Stem Cell Transplant for Multiple Myeloma patients increases the proportion of patients who are progression free three years post randomisation. This will be assessed through patient records, blood and bone marrow samples.
Timepoint [1] 322901 0
Three years post randomisation.
Secondary outcome [1] 380183 0
To assess the impact of the addition of selinexor- dexamethasone to lenalidomide maintenance on progression free survival. This will be assessed through patient records, blood and bone marrow samples.
Timepoint [1] 380183 0
Date of progression.
Secondary outcome [2] 380342 0
To compare Overall Survival (OS), in patients receieving selinexor- dexamethasone lenalidomide maintenance as compared to Lenaidomide maintenance. This will be assessed through patient records, blood and bone marrow samples.
Timepoint [2] 380342 0
Date of Death

Eligibility
Key inclusion criteria
• Patient has voluntarily agreed and has given written consent to both the main study and correlative study
• greater or equal to 17 years of age
• Diagnosed with MM
• Patients must have a diagnosis of symptomatic MM and be eligible for front-line melphalan conditioned ASCT and with greater than 2x106 CD34/kg available for ASCT
• Have undergone at least 4-6 cycles of up-front therapy containing a proteasome inhibitor (PI) and/or immunomodulatory drug (IMID)
• Diagnostic (pre induction) bone marrow paraffin-embedded trephine (10 cut slides) available.
• 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).
• Patients must meet the following clinical laboratory criteria:
o Absolute neutrophil count (ANC) greater than or equal to 1,000/mm3 and platelet count greater than or equal to 75,000/mm3. 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 xULN.
o Calculated creatinine clearance greater than or equal to 30 mL/min per Cockcroft-Gault equation.

Minimum age
17 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrolment.
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
• Systemic treatment, within 14 days before the first dose of selinexor, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort.
• Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive.
• 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.
• Diagnosed or treated for another malignancy within 2 years before study enrolment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• 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, selinexor or dexamethasone.


Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment outside Australia
Country [1] 22360 0
New Zealand
State/province [1] 22360 0

Funding & Sponsors
Funding source category [1] 304987 0
Commercial sector/Industry
Name [1] 304987 0
Karyopharm Therapeutics, Inc
Address [1] 304987 0
Karyopharm Therapeutics, Inc
85 Wells Avenue,
Suite 210,
Newton
MA 02459
Country [1] 304987 0
United States of America
Primary sponsor type
Other Collaborative groups
Name
Australian Leukeamia and Lymphoma Group (ALLG)
Address
ALLG
35 Elizabeth St
Richmond
Victoria
3121
Country
Australia
Secondary sponsor category [1] 305348 0
None
Name [1] 305348 0
Address [1] 305348 0
Country [1] 305348 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 305392 0
St Vincent's Melbourne Human Research Ethics Committee
Ethics committee address [1] 305392 0
41 Victoria Parade,
Fitzroy
Victoria 3065
Ethics committee country [1] 305392 0
Australia
Date submitted for ethics approval [1] 305392 0
01/07/2020
Approval date [1] 305392 0
Ethics approval number [1] 305392 0

Summary
Brief summary
This purpose of this study to determine whether the addition of selinexor-dexamethasone 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 and dexamethasone 20mg, orally, weekly.

If well tolerated, after cycle 4 Lenalidomide may be increased to 15mg, orally, once a day for 21 days.
If well tolerated after cycle 1, Selinexor may be increased to 60mg, orally, weekly.
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100218 0
A/Prof Hang Quach
Address 100218 0
St Vincent's Hospital
41 Victoria Parade,
Fitzroy
Victoria 3065
Country 100218 0
Australia
Phone 100218 0
+61 3 93212030
Fax 100218 0
Email 100218 0
hang.quach@svha.org.au
Contact person for public queries
Name 100219 0
Ms Delaine Smith
Address 100219 0
ALLG
35 Elizabeth Street
Richmond
Victoria 3121
Country 100219 0
Australia
Phone 100219 0
+61 3 8373 9701
Fax 100219 0
Email 100219 0
delaine.smith@allg.org.au
Contact person for scientific queries
Name 100220 0
Ms Delaine Smith
Address 100220 0
ALLG
35 Elizabeth Street
Richmond
Victoria 3121
Country 100220 0
Australia
Phone 100220 0
+61 3 8373 9701
Fax 100220 0
Email 100220 0
delaine.smith@allg.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual patient data will not be shared publically. Aggregate patient data and final results will be presented in the final report.
What supporting documents are/will be available?
No other documents available
Summary results
No Results