Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000291987
Ethics application status
Approved
Date submitted
20/02/2020
Date registered
4/03/2020
Date last updated
28/05/2024
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 with Lenalidomide and Lenalidomide alone for patients with newly diagnosed Multiple Myeloma undergoing Autologous stem cell transplant.
Scientific title
An ALLG phase 3 randomised trial of Selinexor and Lenalidomide - 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
SeaLAND
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.
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.
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 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 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 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 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.
Minimum age
18 Years
Maximum age
No limit
Sex
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.
• 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.

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
Safety review:
• 1st Interim Safety Review: After the 10th patients have completed the 2nd cycle of treatment.
• 2nd Interim Safety Review: After the 20th patients have completed the 2nd cycle of treatment.
• 1st futility assessment: After the 30th patient in the Selinexor and lenalidomide arm has completed a minimum of 6 months follow up. If fewer than 20 patients are alive and progression free following this analysis, then consideration will be given to stopping the study or altering the design.
• The primary analysis will occur 3 years after the last patient accrued. Patients will be followed up for 4 years after the last patient enrolment on clinical study.
• The final update on safety and efficacy will be based on additional data collected in the follow-up phase which will finish when the last patient remaining on study has had his/her 3-year follow-up assessment.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/08/2020
Actual
18/01/2021
Date of last participant enrolment
Anticipated
30/06/2024
Actual
Date of last data collection
Anticipated
25/11/2027
Actual
Sample size
Target
232
Accrual to date
192
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 20682 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [2] 20683 0
The Alfred - Melbourne
Recruitment hospital [3] 20684 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [4] 20685 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [5] 20686 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [6] 20687 0
Townsville University Hospital - Douglas
Recruitment hospital [7] 20688 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [8] 20689 0
Concord Repatriation Hospital - Concord
Recruitment hospital [9] 20690 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [10] 20691 0
Border Medical Oncology - Albury
Recruitment hospital [11] 20692 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [12] 20693 0
Lismore Base Hospital - Lismore
Recruitment hospital [13] 20694 0
Orange Health Service - Orange
Recruitment hospital [14] 20695 0
Launceston General Hospital - Launceston
Recruitment hospital [15] 20696 0
Western Hospital - Footscray - Footscray
Recruitment hospital [16] 20697 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [17] 20698 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [18] 20699 0
Royal Hobart Hospital - Hobart
Recruitment postcode(s) [1] 35481 0
3065 - Fitzroy
Recruitment postcode(s) [2] 35482 0
3004 - Melbourne
Recruitment postcode(s) [3] 35483 0
3084 - Heidelberg
Recruitment postcode(s) [4] 35484 0
3220 - Geelong
Recruitment postcode(s) [5] 35485 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 35486 0
4814 - Douglas
Recruitment postcode(s) [7] 35487 0
3168 - Clayton
Recruitment postcode(s) [8] 35488 0
2139 - Concord
Recruitment postcode(s) [9] 35489 0
3000 - Melbourne
Recruitment postcode(s) [10] 35490 0
2640 - Albury
Recruitment postcode(s) [11] 35491 0
6150 - Murdoch
Recruitment postcode(s) [12] 35492 0
2480 - Lismore
Recruitment postcode(s) [13] 35493 0
2800 - Orange
Recruitment postcode(s) [14] 35494 0
7250 - Launceston
Recruitment postcode(s) [15] 35495 0
3011 - Footscray
Recruitment postcode(s) [16] 35496 0
5000 - Adelaide
Recruitment postcode(s) [17] 35497 0
2010 - Darlinghurst
Recruitment postcode(s) [18] 35498 0
7000 - Hobart
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
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
Approved
Ethics committee name [1] 305392 0
St Vincent's Melbourne Human Research Ethics Committee
Ethics committee address [1] 305392 0
Ethics committee country [1] 305392 0
Australia
Date submitted for ethics approval [1] 305392 0
01/07/2020
Approval date [1] 305392 0
21/09/2020
Ethics approval number [1] 305392 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100218 0
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 9231 3189
Fax 100218 0
Email 100218 0
hang.quach@svha.org.au
Contact person for public queries
Name 100219 0
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
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 Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseOverall survival as a primary end point in multiple myeloma trials.2022https://dx.doi.org/10.1038/s41571-022-00665-7
N.B. These documents automatically identified may not have been verified by the study sponsor.