Selinexor, cyclophosphamide and prednisolone compared to cyclophosphamide and prednisolone in patients with multiple myeloma

Phase 1

• Conditions: Multiple myeloma; MedDRA version: 20.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001736-19-GB
• Lead Sponsor: niversity of Leeds

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-10-10
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Able to give informed consent and willing to follow study protocol assessments
2. Aged 18 years or over
3. Participants with confirmed myeloma based on International Myeloma Working Group (IMWG) criteria Rajkumar et al. (2014)
4. Measurable disease with at least one of the following:
- Paraprotein =5g/L
- Serum free light chains =100mg/L with abnormal ratio for light chain only myeloma
- Bence Jones protein =200mg/L
5. Participants with relapsed or relapsed refractory myeloma who have received = 2 prior anti-myeloma treatments including a proteasome inhibitor and lenalidomide, and now require further treatment
6. Patients for which cyclophosphamide and prednisone alone would be a suitable treatment
7. Eastern Cooperative Oncology Group (ECOG) performance status of = 2
8. Female participants of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception) and have a negative urine pregnancy test at screening. Male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female participants, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment
9. Required laboratory values within 14 days prior to randomisation:
- Platelet count =50x109/L. Platelet count of 30-50 is acceptable if bone marrow aspirate or trephine shows tumour replacement of >50%. Platelet support is permitted within 14 days prior to randomisation, although platelet transfusions to help participants meet eligibility criteria are not allowed within 72 hours prior to the blood sample to confirm protocol eligibility
- Absolute neutrophil count =1.0 x 109/L. Growth factor support is not permitted within 14 days prior to randomisation
- Haemoglobin = 90 g/L. Blood support is permitted
- Alanine transaminase (ALT) and / or aspartate transaminase (AST) =3 x upper limit of normal
- Creatinine clearance = 30 ml/min (using Cockcroft Gault formula)
- Bilirubin =1.5 x upper limit of normal

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 45

Exclusion Criteria

Participants meeting any of the following exclusion criteria are not eligible to take part in this trial:

1. The following participants will be excluded:
- those with non-measurable disease
- those with a solitary bone or solitary extramedullary plasmacytoma
- plasma cell leukaemia
2. Participants with a history of malignancy (other than myeloma) within 5 years before the date of randomisation (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that, in the opinion of the investigator, with concurrence with the Chief Investigator, is considered cured with minimal risk of recurrence within 5 years)
3. Participants with a known or underlying uncontrolled concurrent illness that, in the investigator’s opinion, would make the administration of the study drug hazardous or circumstances that could limit compliance with the study, including, but not limited to the following:
- acute or chronic graft versus host disease,
- uncontrolled hypertension,
- symptomatic congestive heart failure,
- unstable angina pectoris,
- myocardial infarction within past 6 months,
- uncontrolled cardiac arrhythmia,
- active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B or C) hepatitis
Ocular herpes simplex
- psychiatric or social conditions that may interfere with participant compliance,
- uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral
- or any other condition (including laboratory abnormalities) that in the opinion of the Investigator places the participant at unacceptable risk for adverse outcome if he/she were to participate in the study
4. Participants who have previously received Selinexor.
5. Previous anti-tumour therapies including investigational medicinal products at any dose within 28 days before the start of protocol treatment. (NB: Prednisone up to a dose of 175 mg per week may be given between screening and the beginning of treatment if medically required but should be stopped before trial treatment starts. Bisphosphonates for bone disease are also permitted).
6. Participants with a history of a refractory nausea, diarrhoea, vomiting, malabsorption, gastrointestinal surgery or other procedures or conditions that might, in the opinion of the Investigator, interfere with the absorption or swallowing of the study drug(s)
7. Female participants who are lactating or have a positive pregnancy test at screening
8. Known allergy or intolerance to any of the study medications, their analogues, or excipients in the various formulations of any agent
9. Major surgery within 14 days prior to randomisation
10. Radiotherapy within 7 days prior to randomisation for palliative pain control or therapeutic radiotherapy within 14 days prior to randomisation
11. Chemotherapy or immunotherapy or any other anticancer therapy within 2 weeks prior to Cycle 1 Day 1 or radio-immunotherapy 4 weeks prior to Cycle 1 Day 1 (except steroids in the doses outlined above)
12. Myeloma involving the Central Nervous System

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified