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Trial registered on ANZCTR


Registration number
ACTRN12621001361897p
Ethics application status
Not yet submitted
Date submitted
17/08/2021
Date registered
8/10/2021
Date last updated
8/10/2021
Date data sharing statement initially provided
8/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A single arm, open-label study of Exportin 1 inhibitor selinexor in relapsed/refractory central nervous system (CNS) Lymphoma and in relapsed/refractory CNS Myeloma
Scientific title
A single arm, open-label study of efficacy and safety of the Exportin 1 inhibitor selinexor in relapsed/refractory CNS Lymphoma and in relapsed/refractory CNS Myeloma
Secondary ID [1] 305068 0
AMaRC 20-02
Universal Trial Number (UTN)
Trial acronym
EXCLAIM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Central nervous system diffuse large B cell lymphoma 323274 0
Central nervous system myeloma 323646 0
Condition category
Condition code
Cancer 320848 320848 0 0
Myeloma
Cancer 321186 321186 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 321187 321187 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All patients (10 patients with central nervous system (CNS) diffuse large B cell lymphoma (DLBCL) and 10 patients with CNS myeloma) will be administered the following treatment at the same time in a 28-day (4 weeks) cycle:
Selinexor 80mg orally weekly
Dexamethasone 40mg orally weekly (20mg for patients >75 years)

Treatment will be given until disease progression or unacceptable toxicity, withdrawal of consent whichever occurs first. Adherence is monitored through hospital drug administration records and tablet adherence through drug packet return.
Intervention code [1] 321463 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328646 0
To assess the efficacy of selinexor in relapsed/refractory central nervous system (CNS) Diffuse large B-cell lymphoma (DLBCL) and CNS myeloma via laboratory results (serum assay, spinal fluid, haematology and biochemistry blood panel) and radiology assessment.
Timepoint [1] 328646 0
At the completion of the study, assessed once per month until disease progression or unacceptable toxicity,
Primary outcome [2] 328982 0
To assess the safety of selinexor in relapsed/refractory central nervous system (CNS) Diffuse large B-cell lymphoma (DLBCL) and CNS myeloma via adverse events assessed in accordance with the Common Terminology Criteria for Adverse Events (CTCAE5.0)
Timepoint [2] 328982 0
At the completion of the study, assessed once per month until disease progression or unacceptable toxicity,
Secondary outcome [1] 399804 0
To assess the median progression free survival (PFS) in patients observed by monthly blood serum assay and bone marrow (as required) assessments.
Timepoint [1] 399804 0
At the completion of the study, assessed once per month until disease progression.
Secondary outcome [2] 399805 0
To determine the percentage of patients that achieves complete response (CR) or partial response (PR) observed by monthly blood serum assay and bone marrow (as required) assessments.
Timepoint [2] 399805 0
At the completion of the study

Eligibility
Key inclusion criteria
1. Age 18 years old or older
2. Willing and able to provide written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
3. Eastern Cooperative Oncology Group (ECOG) equal to or less than 2
4. Patients with relapsed/refractory CNS lymphoma according to the current World Health Organization classification, having had 1 line of induction treatment or more with no clinically-appropriate viable alternative options available. Patients with synchronous systemic involvement may be eligible after discussion with the CPI.
5. Patients with CNS multiple myeloma according to the current World Health Organization classification, with no clinically-appropriate alternative treatment available. Patients with systemic involvement are eligible.
6. Patients should have measurable CNS disease on imaging/scans, or leptomeningeal disease evident on CSF analysis via lumbar punctures.
7. Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
8. Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment
9. Adequate hepatic function within 28 days prior to C1D1:
a. total bilirubin equal to or less than 1.5 × upper limit of normal (ULN) (except patients with Gilbert’s syndrome who must have a total bilirubin of equal to or less than 3 × ULN), and
b. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to equal to or less than 2 × ULN.
10. Adequate renal function within 28 days prior to C1D1 as determined by serum creatinine of equal to or less than 132 µmol/L OR estimated creatinine clearance of equal to or greater than 30 mL/min, calculated using the Cockcroft and Gault formula (140 – Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female (Cockcroft 1976).
11. Adequate hematopoietic function within 7 days prior to C1D1:
a. total white blood cell (WBC) count equal to or greater than 1.5 x 10^9/L ,
b. absolute neutrophil count equal to or greater than 1.0 x 10^9/L
c. hemoglobin equal to or greater than 85 g/L and
d. platelet count equal to or greater than 75 x 10^9/L (patients for whom <50% of bone marrow nucleated cells are plasma cells) or equal to or greater than 50 10^9/L (patients for whom equal to or greater than 50% of bone marrow nucleated cells are plasma cells).
12. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), and platelet stimulators (eg, eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study.
13. Patients must have at least a 2-week interval from the last red blood cell (RBC) and/or platelet transfusion prior to the Screening hemoglobin assessment (Patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study.)
14. Female patients of childbearing potential must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment.
15. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as defined below: With a female partner of childbearing potential or pregnant female partners, men must remain abstinent or use a condom plus an additional contraceptive method.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has received selinexor or another XPO1 inhibitor previously.
2. Prior malignancy that required treatment or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to randomization. Cancer treated with curative intent for >5 years previously and without evidence of recurrence will be allowed.
3. Has any concurrent medical condition or disease (eg, uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures.
4. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
5. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
6. Pregnant or breastfeeding females.
7. Life expectancy of less than 12 weeks.
8. Major surgery within 4 weeks prior to C1D1.
9. Active, unstable cardiovascular function, as indicated by the presence of:
a) Symptomatic ischemia, or
b) Uncontrolled clinically significant conduction abnormalities (eg, patients with ventricular tachycardia on anti-arrhythmics are excluded; patients with first degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or
c) Congestive heart failure of New York Heart Association Class equal to or greater than 3 or known left ventricular ejection fraction less than 40%, or
d) Myocardial infarction within 3 months prior to C1D1.
10. Known active human immunodeficiency virus (HIV) infection or HIV seropositivity.
11. Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen.
12. Any active gastrointestinal dysfunction interfering with the patient’s ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
13. Inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (CPGO) (NCCN CPGO) for antiemesis and anorexia/cachexia (palliative care).
14. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.
15. Contraindication to any of the required concomitant drugs or supportive treatments.
16. Patients unwilling or unable to comply with the protocol requirements
17. Previous hypersensitivity to selective inhibitor of nuclear export (SINE) drugs.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2021
Actual
Date of last participant enrolment
Anticipated
1/12/2024
Actual
Date of last data collection
Anticipated
1/12/2025
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 20280 0
The Alfred - Melbourne
Recruitment hospital [2] 20281 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 35019 0
3004 - Melbourne
Recruitment postcode(s) [2] 35020 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 309467 0
Other Collaborative groups
Name [1] 309467 0
Australasian Myeloma Research Consortium
Country [1] 309467 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Myeloma Research Consortium
Address
55 Commercial Rd, Melbourne VIC 3004
Country
Australia
Secondary sponsor category [1] 310435 0
None
Name [1] 310435 0
Address [1] 310435 0
Country [1] 310435 0

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 309256 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 309256 0
55 Commercial Road
Melbourne VIC 3004
Ethics committee country [1] 309256 0
Australia
Date submitted for ethics approval [1] 309256 0
18/10/2021
Approval date [1] 309256 0
Ethics approval number [1] 309256 0

Summary
Brief summary
The purpose of this study is to determine whether the combination of Selinexor and Dexamethasone combined improves response to treatment.

Who is it for?
You may be eligible to participate in this trial if you are aged 18 years or over, you have been diagnosed with either central nervous system (CNS) diffuse large B cell lymphoma (DLBCL) or myeloma.

Study Details
Eligible participants will receive Selinexor and Dexamethasone. Treatment (each cycle is 28 days) will be given until disease progression, unacceptable toxicity, or withdrawal of consent.
Participants will be required to have blood samples taken at the beginning of each cycle along with a medical exam in order for researchers to monitor whether the treatment is safe and whether it is effectively treating the myeloma.
It is hoped that the findings of this trial will establish the benefits of this combination for patients with central nervous system (CNS) diffuse large B cell lymphoma (DLBCL) and myeloma.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113514 0
Prof Andrew Spencer
Address 113514 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 113514 0
Australia
Phone 113514 0
+61 390763393
Fax 113514 0
+61390765531
Email 113514 0
andrew.spencer@monash.edu
Contact person for public queries
Name 113515 0
Mr Khoa Le
Address 113515 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 113515 0
Australia
Phone 113515 0
+61 390767851
Fax 113515 0
+61390765531
Email 113515 0
khoa.le@alfred.org.au
Contact person for scientific queries
Name 113516 0
Prof Andrew Spencer
Address 113516 0
Alfred Hospital
55 Commercial Road
Melbourne VIC 3004
Country 113516 0
Australia
Phone 113516 0
+61 390763393
Fax 113516 0
+61390765531
Email 113516 0
andrew.spencer@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
No additional documents have been identified.