Amyloidosis Clinical Trial
Official title:
A Multicentre Open Label Phase II Study of Daratumumab in AL Amyloidosis Patients Not in VGPR or Better
This is a Phase II, single-arm, multicentre study of Daratumumab (16mg/kg IV route) in adult patients with Light-Chain (AL) Amyloidosis who are not in VGPR or better after previous treatment. A sample size of 40 patients who meet all eligibility criteria will be enrolled to receive study treatment. Patients will receive treatment until either disease progression or toxicity has occurred with a maximum planned of six 28-day cycles. Daratumumab will be administrated every week for the first 2 cycles then. every 2 weeks from cycle 3 through cycle 6. Patients will also receive best supportive care (BSC) to mitigate Daratumumab side-effects, and to address underlying Amyloidosis, including blood product transfusions, antimicrobials, and (as appropriate) growth factors including granulocyte colony-stimulating factors for neutropenia, erythropoietin for anaemia, and/or transfusions for thrombocytopenia
Systemic AL amyloidosis is a rare disease caused by the deposition of misfolded monoclonal immunoglobulin free light chains (FLC) in various tissues and organs. It is usually associated with a clonal plasma cell dyscrasia with a low tumour burden. Treatment of AL amyloidosis relies mainly on chemotherapy aimed at suppressing the underlying plasma cell clone secreting monoclonal FLC. The organ responses and the survival are greatly influenced by the degree of hematological response evaluated by the decrease in serum FLC that has been the principal endpoint in recent trials in AL amyloidosis. The goal of treatment is to reach at least a very good partial response (VGPR) defined as a difference between the involved FLC and the normal <40 mg/l. Over the last 2 years, Daratumumab, a novel, high-affinity, therapeutic, human monoclonal antibodies (mAb) that specifically recognizes the CD38 epitope has emerged as a breakthrough targeted therapy for patients with myeloma. Taking into account that, in 90% of AL patients, the monoclonal cells producing amyloidogenic FLC are Cluster of Differentiation 38 (CD38) expressing plasma cells Daratumumab should be a promising treatment in AL amyloidosis. The study will consist of 4 steps: - A 21 day screening period This period start with screening visit which may occurs up to 21 days before the first study drug administration. After signature of the informed consent form, procedures will be performed to ensure patient meet all inclusion/exclusion criteria and document health status to receive study treatment. These assessments will include quality of life questionnaires - A treatment period Patient eligible to enter the study will receive 6 cycles of 28 days of intra venous Daratumumab. During cycles 1 and 2, Daratumumab will be administered weekly at days 1, 8, 15, and 22 then from cycles 3 to 6, Daratumumab will be administered every two weeks at days 1 and 15. Patient will have assessments at the ignition of a new cycle to document haematological and organs response and intra cycle to watch for toxicities. - An end of study visit (when PD or unacceptable adverse events occurs, or planned end of study visit). Study procedures will be performed at 28 days (± 15) after the last dose of study medication for all patients, including early termination patients. - Followup period After treatment discontinuation, followup will be made to the patient every 3 months for at least 1 year to inquire about the patient's hematological and organ status, general health, and information on any new medical events. DOSING REGIMEN Daratumumab. Six 28-day cycles, 16 mg/kg administered by IV route, During cycle 1 and 2, Daratumumab will be administered weekly at days 1, 8, 15, and 22 For cycles 3 to 6, Daratumumab will be administered every other week at days 1 and 15 ;
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 |
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 | |
Completed |
NCT02545907 -
A Dose Escalation Study of Carfilzomib Taken With Thalidomide and Dexamethasone in Relapsed AL Amyloidosis
|
Phase 1/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 |
NCT05235269 -
A Study to Evaluate Organ Level Uptake Repeatability of 124I AT-01 in Subjects With Systemic Amyloidosis
|
Phase 2 | |
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 | |
Completed |
NCT02716103 -
Assessment of Minimal Residual Disease (MRD) After Antineoplastic Treatment in Patients With AL Amyloidosis
|