Daratumumab Therapy for Patients With Refractory or Relapsed AL Amyloidosis (AMYDARA)
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|ClinicalTrials.gov Identifier: NCT02816476|
Recruitment Status : Completed
First Posted : June 28, 2016
Last Update Posted : July 9, 2021
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
|Condition or disease||Intervention/treatment||Phase|
|Amyloidosis||Drug: Daratumumab||Phase 2|
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.
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
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicentre Open Label Phase II Study of Daratumumab in AL Amyloidosis Patients Not in VGPR or Better|
|Actual Study Start Date :||September 2016|
|Actual Primary Completion Date :||October 5, 2019|
|Actual Study Completion Date :||October 2020|
Patient will receive Daratumumab every week for the first 2 cycles then every 2 weeks from cycle 3 through cycle 6.
- Overall Response Rate [ Time Frame: After 6 cycles treatment (6 months). ]Overall Response Rate (CR+VGPR) at the completion of 6 cycles of Daratumumab using the new response criteria (J Clin Oncol, 2012. 30(36): p. 4541-9.
- Number of participants with treatment-related adverse events as assessed by NCI-CTCAE V4.03. [ Time Frame: Every month during 1 year ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02816476
|CHU de Caen|
|Caen, France, 14000|
|CHU de Limoges|
|Limoges, France, 87042|
|CHU de Lyon Sud|
|APHP - Necker|
|APHP - Saint Antoine|
|APHP - Saint Louis|
|CHU de Rennes|
|Amyloidosis Research and Treatment Center|