The SABLe study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Odense University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

9 Aug 2021 → ongoing

Decision date (initial)

2024-11-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512276-35-00

EudraCT number

2020-006060-89

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

ORR (defined as ≥PR) at end of induction, EoI (16 cycles)

Secondary objectives 15

1. Rate of ≥VGPR
2. Rate of MRD negativity
3. Time to response
4. Time to at least VGPR
5. Evaluate toxicity rates , including rates of secondary primary malignancies
6. Rates of polyneuropathy
7. Rates of thrombosis
8. Need of dose reduction
9. Discontinuation because of AEs
10. Patient reported outcomes (PRO) on toxicity
11. Patient-reported outcomes on Quality of Life (QoL)
12. Overall Survival (OS)
13. Progression Free Survival (PFS)
14. Time to Next Treatment (TNT)
15. Focused gene expression analysis for genes predicting response to selinexor

Conditions and MedDRA coding

Multiple Myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Age > 18 years
2. Willing and able to provide written informed consent in accordance with national, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of ≤ 2. ECOG 3 allowed if caused by myeloma
4. Newly diagnosed multiple myeloma with treatment demanding disease as defined by IMWG (Rajkumar, Dimopoulos et al. 2014) and measurable disease defined as 5. as defined IMWG 2016 criteria (Table 5) (Kumar, Paiva et al. 2016)
5. By treating physician considered in-eligible for high-dose therapy with stem-cell transplant
6. Patients must have received no prior chemotherapy for multiple myeloma. Patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis). Patients must have received no prior steroid treatment for myeloma with the exception of a maximum of 14 days of treatment for symptom control (including dexamethasone 40mg).
7. Adequate hepatic function within 7 days prior to C1D1: Total bilirubin < 1.5 × upper limit of normal (ULN) (except patients with Gilbert’s syndrome who must have a total bilirubin of < 3 × ULN), and Alanine aminotransferase (ALT) normal to <2 × ULN.
8. Adequate renal function within 7 days prior to C1D1 as determined by estimated GFR of ≥ 30 mL/min, calculated using standard formula
9. Adequate hematopoietic function within 7 days prior to C1D1: Absolute neutrophil count ≥1.0x109/L, and platelet count ≥100x109/L (patients for whom <50% of bone marrow nucleated cells are plasma cells). If cytopenias are due a plasma cell infiltration in the bone marrow (biopsy-proven heavy-marrow involvement, as defined by having at least 30% marrow cellularity, with > 50% of the cells being malignant plasma cells (documented marrow results required)); in this case, although there are no required lower limits of normal for the blood counts, the treating physician must use his/her medical judgment as to the appropriateness of this study therapy for these patients. Erythropoietin-analogues are allowed.
10. Patients must have: At least a 1-week interval from the last platelet transfusion prior to the screening platelet assessment. However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study
11. 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.
12. Patients must be able to take prophylactic anticoagulation as recommended by study
13. Patients with pathologic fractures, infection at diagnosis or symptomatic hyperviscosity must have these conditions attended to prior to registration (i.e., intramedullary rod, I.V. antibiotics, plasmapheresis)

Exclusion criteria 11

1. Has received selinexor or another XPO1 inhibitor previously
2. Has any concurrent medical condition or disease (e.g. uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is likely to interfere with study procedures
3. Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide and selinexor.
4. Pregnant or breastfeeding females
5. Life expectancy of less than 6 months
6. Active, unstable cardiovascular function, as indicated by the presence of: a) Symptomatic ischemia, or b) Uncontrolled clinically significant conduction abnormalities (e.g. 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 ≥3 or known left ventricular ejection fraction <40%, or d) Myocardial infarction within 6 months prior to C1D1
7. 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.
8. 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).
9. 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
10. Contraindication to any of the required concomitant drugs or supportive treatments
11. Patients unwilling or unable to comply with the protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR at end of induction, with response defined according to IMWG response criteria

Secondary endpoints 15

1. VGPR rate at end of induction
2. MRD negativity by NGS at end of induction
3. Time to at least PR from start of treatment
4. Time to at least VGPR from start of treatment
5. Toxicity rates according to NCI-CTCAE v4.03
6. Rates of neuropathy according to NCI-CTCAE
7. Rates of documented thrombosis
8. Rates of administrated vs planned doses
9. Number of patients of patients finalizing all 16 cycles of planned induction
10. Toxicity rates (frequency, severity and interference) during treatment according to NCI PRO-CTCAE registrations
11. Change from baseline to end of treatment in the key PRO domains of functioning (physical, social and emotional) overall QoL and symptoms of fatigue and nausea
12. OS
13. PFS
14. TNT
15. Changes in gene expression at baseline from patients responding and not-responding to selinexor

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odense University Hospital

Sponsor organisation

Odense University Hospital

Address

J B Winsloews Vej 4

City

Odense C

Postcode

5000

Country

Denmark

Scientific contact point

Organisation

Odense University Hospital

Contact name

Department of Hematology, Odense University Hospital

Public contact point

Organisation

Odense University Hospital

Contact name

Department of Hematology, Odense University Hospital

Third parties 1

Locations

3 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications