Amyloidosis Clinical Trial
Official title:
A Single Arm Open Labeled Multicentre Phase 1b Dose Escalation Study of Carfilzomib Taken in Combination With Thalidomide and Dexamethasone in Relapsed AL Amyloidosis
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.
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. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT04893889 -
Substudy (NCT04456582): Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Two-dimensional Shear Wave Elastography) in Patients With Amyloidosis and Fabry Disease.
|
N/A | |
| Withdrawn |
NCT04943302 -
Isatuximab and Bendamustine in Systemic Light Chain Amyloidosis
|
Phase 2 | |
| Active, not recruiting |
NCT02909036 -
Study of Captisol Enabled Melphalan and Pharmacokinetics for Patients With Multiple Myeloma or Light Chain Amyloidosis That Are Receiving an Autologous Transplant.
|
Phase 1 | |
| Completed |
NCT02816476 -
Daratumumab Therapy for Patients With Refractory or Relapsed AL Amyloidosis
|
Phase 2 | |
| Completed |
NCT01083316 -
Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation for Primary (AL) Amyloidosis
|
Phase 2 | |
| Completed |
NCT01527032 -
Risk-adapted Therapy for Primary Systemic (AL) Amyloidosis
|
Phase 2 | |
| Recruiting |
NCT05263817 -
A Clinical Study of CD19/BCMA CAR-T Cells in the Treatment of Refractory POEMS Syndrome, Amyloidosis, Autoimmune Hemolytic Anemia, and Vasculitis
|
Early Phase 1 | |
| Active, not recruiting |
NCT03201965 -
A Study to Evaluate the Efficacy and Safety of Daratumumab in Combination With Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD) Compared to CyBorD Alone in Newly Diagnosed Systemic Amyloid Light-chain (AL) Amyloidosis
|
Phase 3 | |
| Withdrawn |
NCT02589860 -
Analysis of Oral Mucositis in Patient's Undergoing Melphalan Conditioning and Autologous Stem Cell Transplant
|
||
| Recruiting |
NCT05635266 -
Tissue Repository Providing Annotated Biospecimens for Approved Investigator-directed Biomedical Research Initiatives
|
||
| Completed |
NCT02574676 -
Quality of Life (QOL) Registry for Patients With AL Amyloidosis
|
||
| Active, not recruiting |
NCT02260466 -
Prevalence and Post-surgical Outcomes of CARdiac Wild-type TransthyrEtin amyloidoSIs in Elderly Patients With Aortic steNosis Referred for Valvular Replacement.
|
N/A | |
| Withdrawn |
NCT02462213 -
Prospective Identification of Cardiac Amyloidosis by Cardiac Magnetic Resonance Imaging
|
N/A | |
| Recruiting |
NCT05577819 -
Prevalence and Prediction of ATTR in Ambulatory Patients With HFpEF
|
N/A | |
| Completed |
NCT01406314 -
SAP Depleter Dose Assessment Study in Patients
|
Phase 1 | |
| Not yet recruiting |
NCT04985734 -
Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM) in Patients With Idiopathic Peripheral Neuropathy
|
N/A | |
| Active, not recruiting |
NCT03584022 -
Clinical Trial to Assess the Safety of a Novel Scaffold Biomaterial
|
N/A | |
| Active, not recruiting |
NCT05199337 -
Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis
|
Phase 1/Phase 2 | |
| Active, not recruiting |
NCT05235269 -
A Study to Evaluate Organ Level Uptake Repeatability of 124I AT-01 in Subjects With Systemic Amyloidosis
|
Phase 2 | |
| Completed |
NCT02716103 -
Assessment of Minimal Residual Disease (MRD) After Antineoplastic Treatment in Patients With AL Amyloidosis
|