NCT06212596

Selinexor, Cyclophosphamide and Prednisone in Myeloma

A Randomised Phase II Trial of Selinexor, Cyclophosphamide and Prednisone vs Cyclophosphamide and Prednisone in Relapsed or Refractory Multiple Myeloma (RRMM) Patients

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 66 (actual)
• Sponsor: University of Leeds · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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. Selinexor is the first-in-class selective inhibitor of nuclear export (SINE). Selinexor forms slowly reversible adducts with the substrate binding pocket of Exportin and has been demonstrated to lead to effective cell kill by causing accumulation pro-apoptotic proteins in the nucleus of myeloma cells. To maximise response to this novel drug in a relapsed-refractory setting, Selinexor will be combined with low-dose cyclophosphamide and prednisone. Lower, continuous doses of cyclophosphamide and intermittent doses of prednisone have been chosen to limit toxicity for the triplet regimen in the elderly myeloma patient population. A calibration group will receive cyclophosphamide plus prednisone alone, and will be used to evaluate the validity of the outcome in the experimental group. Participants will be randomised on a 3:1 basis to receive either selinexor + cyclophosphamide + prednisone (SCP) or cyclophosphamide + prednisone (CP). 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. Participants will be recruited from approximately 10 NHS Hospitals throughout the UK.

Conditions

• Relapsed or Refractory Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Selinexor	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.
DRUG	Cyclophosphamide	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)).
DRUG	Prednisone	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.

Timeline

• Start date: 2018-07-16
• Primary completion: 2022-10-25
• Completion: 2023-11-14
• First posted: 2024-01-19
• Last updated: 2024-01-19

Locations

13 sites across 1 country: United Kingdom