NCT02545907

A Dose Escalation Study of Carfilzomib Taken With Thalidomide and Dexamethasone in Relapsed AL Amyloidosis

A Single Arm Open Labeled Multicentre Phase 1b Dose Escalation Study of Carfilzomib Taken in Combination With Thalidomide and Dexamethasone in Relapsed AL Amyloidosis

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: University College, London · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study evaluates the safety and efficacy of carfilzomib used in combination with thalidomide and dexamethasone in patients with relapsed AL amyloidosis. The trial begins with a dose escalation phase, in which the maximum tolerated and recommended dose will be determined. The trial will then open into an expansion phase in which the combination efficacy is assessed.

Detailed description

Amyloidosis is a disorder of protein folding in which normally soluble proteins are deposited as abnormal, insoluble fibrils that progressively disrupt tissue structure and impair function. The treatment of systemic AL amyloidosis has evolved to a risk adapted approach based on the end organ damage, particularly cardiac involvement, and the functional status of the patient. Intensive therapies like high dose melphalan followed by an autologous stem cell transplant are considered for patients with limited organ involvement, younger age and excellent functional status. The majority of patients with AL amyloidosis, however, will not be candidates for ASCT and are generally treated with combination chemotherapy. This therapy may include bortezomib, a proteasome inhibitor which is particularly effective in AL amyloidosis but which may have a severe side-effect profile. Carfilzomib is specific for the chymotrypsin-like active site of the 20S proteasome, is structurally and mechanistically distinct from bortezomib, and has demonstrated less reactivity against non-proteasomal proteases when compared to bortezomib. It also appears to be better tolerated. However, information regarding the use of carfilzomib in the treatment of AL amyloidosis is limited. In the dose escalation phase of this study, a minimum of 6 (3 at dose level 0 and 3 at dose level -1)and a maximum of 18 (6 at dose level 0, 1, and 2) patients will recruited in a 3+3 design with cohorts of between 3 and 6 patients, in order to determine maximum tolerated dose and recommended dose. At the recommended dose level identified, a further 20 (minimum) patients will be recruited to further assess safety and toxicities at the RD.

Conditions

• Amyloidosis

Interventions

Type	Name	Description
DRUG	Carfilzomib	Lyophilized carfilzomib for injection reconstituted with water to a final concentration of 2 mg/mL.
DRUG	Thalidomide	50mg capsule.
DRUG	Dexamethasone	2mg tablet.

Timeline

• Start date: 2017-09-14
• Primary completion: 2019-09-26
• Completion: 2019-10-21
• First posted: 2015-09-10
• Last updated: 2021-04-15
• Results posted: 2021-04-15

Locations

14 sites across 1 country: United Kingdom