Selinexor, Cyclophosphamide and Prednisone in Myeloma

NCT06212596 | Completed Phase 2 DMC

• 2 other identifiers: HM17/952282017-001736-19
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 13

Brief Summary

The trial is designed as a randomised, controlled, open, parallel group, multi-centre phase II trial to evaluate clinical efficacy of selinexor in combination with cyclophosphamide and prednisone.

Conditions

Relapsed or Refractory Multiple Myeloma

Keywords

Myeloma

Outcome Measures

Primary Outcomes (1)

• Progression free survival at 6 months

  To determine whether the addition of selinexor to cyclophosphamide and prednisone may lead to an increased progression free survival

  6 months

Secondary Outcomes (7)

• Number of SAEs, SARs, SUSARs

  3 1/2 years

• Progression free survival

  6 and 12 months

• Maximum response

  6 and 12 months

• Time to maximum response

  6 and 12 months

• Duration of response

  6 and 12 months

Study Arms (2)

Selinexor cylophosphamide prednisone

EXPERIMENTAL

Participants will receive treatment with Selinexor, Cyclophosphamide and Prednisone.

Drug: Selinexor; Drug: Cyclophosphamide; Drug: Prednisone

Cyclophosphamide predinisone

ACTIVE COMPARATOR

Participants will receive treatment with Cyclophosphamide and Prednisone. Participants who experience disease progression on the CP arm, may receive SCP.

Drug: Cyclophosphamide; Drug: Prednisone

Interventions

Selinexor DRUG

Selinexor is a Selective Inhibitor of Nuclear Export (SINE) compound that binds and inactivates Exportin 1 (XPO1), thereby forcing the nuclear retention of key tumour suppressor proteins (TSPs). Selinexor is an oral, first-in-class, potent, slowly reversible, covalent-binding Selective Inhibitor of Nuclear Export (SINE) compound that specifically blocks the karyopherin protein Exportin 1 (XPO1), also called chromosome region maintenance 1.

Selinexor cylophosphamide prednisone

Cyclophosphamide DRUG

Cyclophosphamide is a long used conventional chemotherapy with potent anti-myeloma activity and low toxicity when administered at low doses as in the current protocol (Hajek et al. (2016)). It is being extensively used in combination with novel agents, including bortezomib, lenalidomide, and pomalidomide, and provides a cost-effective and well-tolerated alternative as a combination partner (Morgan et al. (2007); Mai et al. (2015); Baz et al. (2016)).

Cyclophosphamide predinisone; Selinexor cylophosphamide prednisone

Prednisone DRUG

Steroids have been a very effective backbone for every myeloma combination therapy developed so far. Prednisone is the standard steroid in a number of widely used regimens (Mateos et al. (2010);Palumbo et al. (2006)). Decreasing the morbidity associated with high dose steroid use by using better-tolerated regimens addresses a large unmet need of the myeloma patient population.

Cyclophosphamide predinisone; Selinexor cylophosphamide prednisone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to give informed consent and willing to follow all trial protocol assessments
• Aged 18 years or over
• Participants with confirmed myeloma based on International Myeloma Working Group (IMWG) criteria (Rajkumar et al. (2014))
• 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
• 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
• Patients for which cyclophosphamide and prednisone alone would be a suitable treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• 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 trial and for at least 36 months following the last dose of trial treatment
• 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

You may not qualify if:

• The following participants will be excluded:
• those with non-measurable disease
• those with a solitary bone or solitary extramedullary plasmacytoma
• plasma cell leukaemia
• 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)
• Participants with a known or underlying uncontrolled concurrent illness that, in the investigator's opinion, would make the administration of the trial drug hazardous or circumstances that could limit compliance with the trial, 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 (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 4 GradeCTCAE grade ≥2)
• active symptomatic fungal, bacterial, and/or viral infection including known active HIV or known viral (A, B or C) hepatitis
• 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

Sponsors & Collaborators

• University of Leeds: lead

Study Sites (13)

Birmingham Heartlands Hospital

Birmingham, United Kingdom

Location

Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

Leicester Royal Infirmary

Leicester, United Kingdom

Location

Royal Liverpool University Hospital

Liverpool, United Kingdom

Location

St Bartholomew Hospital

London, EC1M 6BQ, United Kingdom

Location

Guys and St Thomas NHS Foundation Trust

London, SE1 9RT, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, W2 1NY, United Kingdom

Location

Royal Marsden Hospital

London, United Kingdom

Location

James Cook University Hospital

Middlesbrough, United Kingdom

Location

Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital

Sheffield, United Kingdom

Location

University Hospital Southampton

Southampton, SO16 6YD, United Kingdom

Location

Royal Stoke University Hospital

Stoke-on-Trent, United Kingdom

Location

Worthing Hospital

Worthing, United Kingdom

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

selinexor; Cyclophosphamide; Prednisone

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Martin Kaiser

  Institute of Cancer Research, United Kingdom

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomised on a 3:1 basis to receive either selinexor + cyclophosphamide + prednisone (SCP) or cyclophosphamide + prednisone (CP). A computer-generated minimisation programme that incorporates a random element will be used to ensure treatment groups are well-balanced for pre-specified factors: * Age (\<60 vs. 60-69 years vs. ≥70 years ) * Number of prior lines of therapy (≤3 vs. \>3) A maximum of 60 participants will be recruited (45 participants in the SCP arm, and 15 participants in the CP arm). Participants who experience disease progression on the CP arm, may receive SCP, once progression has been confirmed by the CTRU and the participant has been deemed eligible to receive SCP. Patients randomised to SCP have no further trial treatment stipulated following SCP therapy. The analysis of the treatment switch phase of the trial is exploratory.

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: January 19, 2024
• Study Start: July 16, 2018
• Primary Completion: October 25, 2022
• Study Completion: November 14, 2023
• Last Updated: January 19, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (13)